Trial Outcomes & Findings for Study to Assess the Efficacy, Safety, and Tolerability of Vixarelimab in Reducing Pruritus in Prurigo Nodularis (NCT NCT03816891)

NCT ID: NCT03816891

Last Updated: 2026-01-13

Results Overview

Participants rated pruritus daily on the Worst Itch \[pruritis\] Numeric Rating Scale (WI-NRS: 0=no pruritus; 10=worst imaginable pruritus). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 240 participants
• Primary outcome timeframe: at Week 8 (Phase 2a); at Week 16 (Phase 2b)
• Results posted on: 2026-01-13

Participant Flow

Participants were randomized 1:1 to receive vixarelimab or placebo in Phase 2a. In Phase 2b, participants were randomized 1:1:1:1:1 to receive 4 different dosing regimens of vixarelimab or placebo in a 16-week Double-Blind Period followed by a 36-week Open-Label-Extension (OLE) Period.

Participant milestones

Measure	Phase 2b - Vixarelimab 540 mg SC Q4W (DBL) Vixarelimab 540 mg SC, every 4 weeks (Q4W) for 16 weeks during the double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2a - Placebo SC QW Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Vixarelimab 360 mg SC QW Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 360 mg SC, Q4W (DBL) Vixarelimab 360 mg SC, Q4W for 16 weeks during the double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Double-Blind Period STARTED	47	26	24	47	47	49
Double-Blind Period Randomized and Treated	47	26	23	47	47	48
Double-Blind Period Completed Treatment	45	23	23	44	47	47
Double-Blind Period COMPLETED	45	24	20	44	47	47
Double-Blind Period NOT COMPLETED	2	2	4	3	0	2
Open-Label Period (Phase 2b Only) STARTED	45	0	0	43	47	46
Open-Label Period (Phase 2b Only) Completed Treatment	38	0	0	38	38	43
Open-Label Period (Phase 2b Only) COMPLETED	38	0	0	38	39	43
Open-Label Period (Phase 2b Only) NOT COMPLETED	7	0	0	5	8	3

Reasons for withdrawal

Measure	Phase 2b - Vixarelimab 540 mg SC Q4W (DBL) Vixarelimab 540 mg SC, every 4 weeks (Q4W) for 16 weeks during the double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2a - Placebo SC QW Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Vixarelimab 360 mg SC QW Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 360 mg SC, Q4W (DBL) Vixarelimab 360 mg SC, Q4W for 16 weeks during the double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Double-Blind Period Withdrawal by Subject	0	2	1	2	0	0
Double-Blind Period Adverse Event	2	0	0	0	0	0
Double-Blind Period Lost to Follow-up	0	0	2	0	0	1
Double-Blind Period Physician Decision	0	0	0	1	0	0
Double-Blind Period Coronavirus Disease (COVID-19)	0	0	0	0	0	1
Double-Blind Period Other	0	0	1	0	0	0
Open-Label Period (Phase 2b Only) Withdrawal by Subject	4	0	0	3	2	0
Open-Label Period (Phase 2b Only) Adverse Event	2	0	0	2	2	1
Open-Label Period (Phase 2b Only) Lack of Efficacy	1	0	0	0	3	0
Open-Label Period (Phase 2b Only) Lost to Follow-up	0	0	0	0	1	1
Open-Label Period (Phase 2b Only) Other	0	0	0	0	0	1

Baseline Characteristics

The Phase 2a and Phase 2b populations were analyzed separately.

Baseline characteristics by cohort

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 540 mg SC Q4W (DBL) n=47 Participants Vixarelimab 540 mg SC, every 4 weeks (Q4W) for 16 weeks during the double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 360 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 360 mg SC, Q4W for 16 weeks during the double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Total n=238 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Phase 2a · Not Hispanic or Latino	21 Participants n=23 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	26 Participants n=26 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	—	—	—	—	47 Participants n=49 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Age, Continuous Phase 2a	52.0 years STANDARD_DEVIATION 15.56 • n=23 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	64.1 years STANDARD_DEVIATION 7.86 • n=26 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	—	—	—	—	58.4 years STANDARD_DEVIATION 13.41 • n=49 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Age, Continuous Phase 2b	—	—	56.7 years STANDARD_DEVIATION 12.18 • n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	55.9 years STANDARD_DEVIATION 13.73 • n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	54.4 years STANDARD_DEVIATION 16.11 • n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	54.8 years STANDARD_DEVIATION 13.35 • n=48 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	55.4 years STANDARD_DEVIATION 13.83 • n=189 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Sex: Female, Male Phase 2a · Female	13 Participants n=23 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	16 Participants n=26 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	—	—	—	—	29 Participants n=49 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Sex: Female, Male Phase 2a · Male	10 Participants n=23 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	10 Participants n=26 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	—	—	—	—	20 Participants n=49 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Sex: Female, Male Phase 2b · Female	—	—	29 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	28 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	28 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	29 Participants n=48 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	114 Participants n=189 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Sex: Female, Male Phase 2b · Male	—	—	18 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	19 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	19 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	19 Participants n=48 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	75 Participants n=189 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Ethnicity (NIH/OMB) Phase 2a · Hispanic or Latino	2 Participants n=23 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=26 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	—	—	—	—	2 Participants n=49 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Ethnicity (NIH/OMB) Phase 2a · Unknown or Not Reported	0 Participants n=23 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=26 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	—	—	—	—	0 Participants n=49 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Ethnicity (NIH/OMB) Phase 2b · Hispanic or Latino	—	—	0 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	5 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	4 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	3 Participants n=48 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	12 Participants n=189 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Ethnicity (NIH/OMB) Phase 2b · Not Hispanic or Latino	—	—	47 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	42 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	43 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	45 Participants n=48 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	177 Participants n=189 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Ethnicity (NIH/OMB) Phase 2b · Unknown or Not Reported	—	—	0 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=48 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=189 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Race (NIH/OMB) Phase 2a · American Indian or Alaska Native	0 Participants n=23 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	1 Participants n=26 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	—	—	—	—	1 Participants n=49 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Race (NIH/OMB) Phase 2a · Asian	2 Participants n=23 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=26 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	—	—	—	—	2 Participants n=49 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Race (NIH/OMB) Phase 2a · Native Hawaiian or Other Pacific Islander	0 Participants n=23 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=26 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	—	—	—	—	0 Participants n=49 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Race (NIH/OMB) Phase 2a · Black or African American	5 Participants n=23 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	3 Participants n=26 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	—	—	—	—	8 Participants n=49 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Race (NIH/OMB) Phase 2a · White	15 Participants n=23 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	21 Participants n=26 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	—	—	—	—	36 Participants n=49 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Race (NIH/OMB) Phase 2a · More than one race	1 Participants n=23 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=26 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	—	—	—	—	1 Participants n=49 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Race (NIH/OMB) Phase 2a · Unknown or Not Reported	0 Participants n=23 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	1 Participants n=26 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	—	—	—	—	1 Participants n=49 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Race (NIH/OMB) Phase 2b · American Indian or Alaska Native	—	—	0 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	1 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	1 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	2 Participants n=48 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	4 Participants n=189 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Race (NIH/OMB) Phase 2b · Asian	—	—	9 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	11 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	3 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	11 Participants n=48 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	34 Participants n=189 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Race (NIH/OMB) Phase 2b · Native Hawaiian or Other Pacific Islander	—	—	0 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=48 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=189 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Race (NIH/OMB) Phase 2b · Black or African American	—	—	3 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	5 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	8 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	6 Participants n=48 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	22 Participants n=189 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Race (NIH/OMB) Phase 2b · White	—	—	31 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	27 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	34 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	29 Participants n=48 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	121 Participants n=189 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Race (NIH/OMB) Phase 2b · More than one race	—	—	1 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	1 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=48 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	2 Participants n=189 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Race (NIH/OMB) Phase 2b · Unknown or Not Reported	—	—	3 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	2 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	1 Participants n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	0 Participants n=48 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	6 Participants n=189 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Weekly Average Worst Itch-Numeric Rating Scale (WI-NRS) Score at Baseline Phase 2a	8.7 score on a scale STANDARD_DEVIATION 0.88 • n=23 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	8.0 score on a scale STANDARD_DEVIATION 1.09 • n=26 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	—	—	—	—	8.3 score on a scale STANDARD_DEVIATION 1.05 • n=49 Participants • The Phase 2a and Phase 2b populations were analyzed separately.
Weekly Average Worst Itch-Numeric Rating Scale (WI-NRS) Score at Baseline Phase 2b	—	—	8.4 score on a scale STANDARD_DEVIATION 0.93 • n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	8.7 score on a scale STANDARD_DEVIATION 0.91 • n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	8.4 score on a scale STANDARD_DEVIATION 1.17 • n=47 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	8.6 score on a scale STANDARD_DEVIATION 0.89 • n=48 Participants • The Phase 2a and Phase 2b populations were analyzed separately.	8.5 score on a scale STANDARD_DEVIATION 0.98 • n=189 Participants • The Phase 2a and Phase 2b populations were analyzed separately.

PRIMARY outcome

Timeframe: at Week 8 (Phase 2a); at Week 16 (Phase 2b)

Population: Modified Intent to Treat (mITT) Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Part 2a: Last Observation Carried Forward (LOCF); Part 2b: Multiple imputation (WI)

Participants rated pruritus daily on the Worst Itch [pruritis] Numeric Rating Scale (WI-NRS: 0=no pruritus; 10=worst imaginable pruritus). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=47 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a & 2b: Percent Change From Baseline in Weekly Average Worst Itch-Numeric Rating Scale (WI-NRS) Score	-50.6 percentage change Standard Error 6.99	-29.4 percentage change Standard Error 6.80	-56.2 percentage change Standard Error 4.84	-51.0 percentage change Standard Error 4.83	-33.0 percentage change Standard Error 4.86	-14.5 percentage change Standard Error 4.76

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period; LOCF.

Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus).

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS at Week 8	52.2 percentage of participants Interval 30.6 to 73.2	30.8 percentage of participants Interval 14.3 to 51.8	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period; LOCF.

At every visit, participants rated the intensity of their average pruritus over previous 3 days on VAS 0-10 line scale (0=no pruritis, 10=worst imaginable pruritis)

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Percent Change From Baseline in Pruritus Visual Analog Scale (VAS) at Week 8	-54.4 percentage change Standard Error 7.03	-32.6 percentage change Standard Error 6.96	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 16: LOCF; Weeks 17-24: participants with an assessment at given time point.

Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus).

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 8	-4.5 score on a scale Standard Error 0.68	-2.7 score on a scale Standard Error 0.43	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 9	-4.2 score on a scale Standard Error 0.65	-2.8 score on a scale Standard Error 0.41	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 10	-4.2 score on a scale Standard Error 0.62	-2.9 score on a scale Standard Error 0.41	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 11	-4.0 score on a scale Standard Error 0.65	-3.2 score on a scale Standard Error 0.43	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 12	-3.9 score on a scale Standard Error 0.63	-2.9 score on a scale Standard Error 0.41	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 13	-4.2 score on a scale Standard Error 0.67	-2.8 score on a scale Standard Error 0.43	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 14	-4.4 score on a scale Standard Error 0.69	-2.7 score on a scale Standard Error 0.45	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 15	-4.3 score on a scale Standard Error 0.69	-2.9 score on a scale Standard Error 0.44	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 16	-4.3 score on a scale Standard Error 0.64	-3.0 score on a scale Standard Error 0.42	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 17	-3.8 score on a scale Standard Error 1.04	-3.1 score on a scale Standard Error 0.64	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 18	-4.3 score on a scale Standard Error 1.05	-3.2 score on a scale Standard Error 0.61	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 19	-4.4 score on a scale Standard Error 1.02	-3.3 score on a scale Standard Error 0.62	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 20	-4.3 score on a scale Standard Error 1.04	-3.6 score on a scale Standard Error 0.69	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 21	-4.3 score on a scale Standard Error 1.03	-3.4 score on a scale Standard Error 0.74	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 22	-4.4 score on a scale Standard Error 1.00	-3.1 score on a scale Standard Error 0.66	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 23	-4.4 score on a scale Standard Error 1.04	-3.1 score on a scale Standard Error 0.72	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 24	-4.3 score on a scale Standard Error 1.03	-2.9 score on a scale Standard Error 0.74	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 7	-4.5 score on a scale Standard Error 0.68	-2.8 score on a scale Standard Error 0.44	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 1	-1.6 score on a scale Standard Error 0.36	-0.8 score on a scale Standard Error 0.29	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 2	-2.4 score on a scale Standard Error 0.47	-1.3 score on a scale Standard Error 0.30	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 3	-2.9 score on a scale Standard Error 0.52	-1.9 score on a scale Standard Error 0.37	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 4	-3.7 score on a scale Standard Error 0.62	-2.3 score on a scale Standard Error 0.42	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 5	-4.2 score on a scale Standard Error 0.66	-2.6 score on a scale Standard Error 0.39	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time Week 6	-4.3 score on a scale Standard Error 0.64	-2.6 score on a scale Standard Error 0.37	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 16: LOCF; Weeks 17-24: participants with an assessment at given time point.

Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 9	-47.0 percentage change Standard Error 6.69	-29.7 percentage change Standard Error 6.50	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 5	-46.6 percentage change Standard Error 6.48	-28.0 percentage change Standard Error 6.29	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 6	-48.3 percentage change Standard Error 6.27	-27.9 percentage change Standard Error 6.10	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 7	-50.5 percentage change Standard Error 7.01	-29.7 percentage change Standard Error 6.81	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 8	-50.6 percentage change Standard Error 6.99	-29.4 percentage change Standard Error 6.80	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 10	-47.9 percentage change Standard Error 6.42	-30.8 percentage change Standard Error 6.24	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 1	-20.2 percentage change Standard Error 4.21	-9.1 percentage change Standard Error 4.09	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 2	-27.3 percentage change Standard Error 5.00	-13.9 percentage change Standard Error 4.86	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 3	-33.6 percentage change Standard Error 5.39	-18.1 percentage change Standard Error 5.24	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 4	-42.3 percentage change Standard Error 6.27	-22.8 percentage change Standard Error 6.10	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 18	-50.9 percentage change Standard Error 10.83	-38.1 percentage change Standard Error 9.84	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 19	-51.2 percentage change Standard Error 10.51	-39.6 percentage change Standard Error 9.55	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 20	-50.1 percentage change Standard Error 10.76	-43.9 percentage change Standard Error 9.77	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 21	-50.2 percentage change Standard Error 11.09	-41.0 percentage change Standard Error 10.07	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 22	-50.3 percentage change Standard Error 10.52	-38.0 percentage change Standard Error 9.55	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 23	-51.7 percentage change Standard Error 11.24	-37.5 percentage change Standard Error 10.21	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 24	-51.8 percentage change Standard Error 11.76	-33.8 percentage change Standard Error 10.68	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 11	-44.8 percentage change Standard Error 6.84	-34.0 percentage change Standard Error 6.65	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 12	-43.9 percentage change Standard Error 6.59	-29.9 percentage change Standard Error 6.41	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 13	-46.3 percentage change Standard Error 6.59	-28.1 percentage change Standard Error 6.41	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 14	-48.9 percentage change Standard Error 6.97	-27.6 percentage change Standard Error 6.78	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 15	-48.8 percentage change Standard Error 6.93	-29.6 percentage change Standard Error 6.74	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 16	-50.4 percentage change Standard Error 6.43	-31.3 percentage change Standard Error 6.25	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 17	-47.0 percentage change Standard Error 10.96	-36.5 percentage change Standard Error 10.40	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 8: LOCF; Weeks 9-24: participants with an assessment at given time point.

Participants rated intensity of their average pruritus over previous 3 days on VAS 0-10 line scale (0=no pruritis, 10=worst imaginable pruritis)

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 7	-5.0 units on a scale Standard Error 0.69	-3.2 units on a scale Standard Error 0.56	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 8	-5.0 units on a scale Standard Error 0.72	-3.0 units on a scale Standard Error 0.48	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 1	-1.9 units on a scale Standard Error 0.55	-1.4 units on a scale Standard Error 0.33	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 2	-2.9 units on a scale Standard Error 0.62	-1.8 units on a scale Standard Error 0.51	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 3	-3.5 units on a scale Standard Error 0.63	-2.2 units on a scale Standard Error 0.52	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 4	-4.5 units on a scale Standard Error 0.72	-3.3 units on a scale Standard Error 0.58	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 5	-4.5 units on a scale Standard Error 0.70	-2.7 units on a scale Standard Error 0.50	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 6	-4.7 units on a scale Standard Error 0.75	-2.9 units on a scale Standard Error 0.54	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 9	-4.3 units on a scale Standard Error 1.08	-3.8 units on a scale Standard Error 0.61	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 10	-5.0 units on a scale Standard Error 0.71	-3.7 units on a scale Standard Error 0.49	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 11	-4.7 units on a scale Standard Error 1.27	-4.3 units on a scale Standard Error 0.58	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 12	-4.8 units on a scale Standard Error 0.66	-3.8 units on a scale Standard Error 0.46	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 13	-4.6 units on a scale Standard Error 1.20	-3.5 units on a scale Standard Error 0.64	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 14	-4.8 units on a scale Standard Error 1.10	-3.7 units on a scale Standard Error 0.68	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 15	-4.5 units on a scale Standard Error 1.16	-3.9 units on a scale Standard Error 0.69	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 16	-5.1 units on a scale Standard Error 0.70	-3.3 units on a scale Standard Error 0.50	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 18	-4.8 units on a scale Standard Error 1.14	-3.0 units on a scale Standard Error 0.67	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 20	-4.6 units on a scale Standard Error 1.19	-2.9 units on a scale Standard Error 0.74	—	—	—	—
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 24	-4.9 units on a scale Standard Error 1.19	-2.9 units on a scale Standard Error 0.80	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 8: LOCF; Weeks 9-24: participants with an assessment at given time point.

Participants rated intensity of their average pruritus over previous 3 days on VAS 0-10 line scale (0=no pruritis, 10=worst imaginable pruritis). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 1	-18.4 percentage change Standard Error 5.45	-15.8 percentage change Standard Error 5.40	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 2	-28.2 percentage change Standard Error 6.74	-18.3 percentage change Standard Error 6.67	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 11	-50.5 percentage change Standard Error 10.59	-51.2 percentage change Standard Error 9.02	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 14	-50.4 percentage change Standard Error 10.25	-44.2 percentage change Standard Error 8.73	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 15	-46.0 percentage change Standard Error 10.66	-47.6 percentage change Standard Error 9.08	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 3	-36.8 percentage change Standard Error 6.53	-19.2 percentage change Standard Error 6.46	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 4	-48.9 percentage change Standard Error 7.60	-33.1 percentage change Standard Error 7.52	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 5	-47.5 percentage change Standard Error 6.88	-27.9 percentage change Standard Error 6.81	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 6	-50.0 percentage change Standard Error 7.81	-31.8 percentage change Standard Error 7.73	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 7	-54.3 percentage change Standard Error 7.41	-33.6 percentage change Standard Error 7.33	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 8	-54.4 percentage change Standard Error 7.03	-32.6 percentage change Standard Error 6.96	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 9	-42.5 percentage change Standard Error 9.51	-47.2 percentage change Standard Error 8.10	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 10	-54.0 percentage change Standard Error 6.92	-40.0 percentage change Standard Error 6.71	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 12	-53.4 percentage change Standard Error 6.19	-40.2 percentage change Standard Error 6.00	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 13	-48.3 percentage change Standard Error 10.88	-43.0 percentage change Standard Error 9.26	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 16	-56.5 percentage change Standard Error 6.70	-35.6 percentage change Standard Error 6.50	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 18	-50.2 percentage change Standard Error 11.56	-39.3 percentage change Standard Error 10.44	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 20	-48.8 percentage change Standard Error 12.47	-37.1 percentage change Standard Error 11.26	—	—	—	—
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time Week 24	-50.4 percentage change Standard Error 12.32	-36.6 percentage change Standard Error 11.11	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 8: LOCF; Weeks 10-24: participants with an assessment at given time point.

Administered every 2 visits, the 5-D Pruritus Scale evaluates pruritus in 5 domains: duration, degree, direction, disability and distribution. The scores from each domain are added together to obtain a total 5-D score ranging from 5 (no pruritus) to 25 (most severe pruritus).

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Change From Baseline in 5-D Pruritus Total Score Over Time Week 2	-5.8 score on a scale Standard Error 0.95	-2.7 score on a scale Standard Error 0.57	—	—	—	—
Phase 2a: Change From Baseline in 5-D Pruritus Total Score Over Time Week 4	-6.7 score on a scale Standard Error 1.12	-3.9 score on a scale Standard Error 0.76	—	—	—	—
Phase 2a: Change From Baseline in 5-D Pruritus Total Score Over Time Week 6	-7.2 score on a scale Standard Error 1.09	-4.2 score on a scale Standard Error 0.76	—	—	—	—
Phase 2a: Change From Baseline in 5-D Pruritus Total Score Over Time Week 8	-7.7 score on a scale Standard Error 1.17	-4.3 score on a scale Standard Error 0.78	—	—	—	—
Phase 2a: Change From Baseline in 5-D Pruritus Total Score Over Time Week 10	-7.7 score on a scale Standard Error 1.18	-5.0 score on a scale Standard Error 0.77	—	—	—	—
Phase 2a: Change From Baseline in 5-D Pruritus Total Score Over Time Week 12	-7.4 score on a scale Standard Error 1.16	-4.8 score on a scale Standard Error 0.83	—	—	—	—
Phase 2a: Change From Baseline in 5-D Pruritus Total Score Over Time Week 14	-7.1 score on a scale Standard Error 1.72	-4.7 score on a scale Standard Error 1.13	—	—	—	—
Phase 2a: Change From Baseline in 5-D Pruritus Total Score Over Time Week 16	-7.5 score on a scale Standard Error 1.26	-4.6 score on a scale Standard Error 0.72	—	—	—	—
Phase 2a: Change From Baseline in 5-D Pruritus Total Score Over Time Week 18	-6.8 score on a scale Standard Error 1.60	-3.4 score on a scale Standard Error 1.42	—	—	—	—
Phase 2a: Change From Baseline in 5-D Pruritus Total Score Over Time Week 20	-6.8 score on a scale Standard Error 1.67	-3.5 score on a scale Standard Error 1.40	—	—	—	—
Phase 2a: Change From Baseline in 5-D Pruritus Total Score Over Time Week 24	-7.9 score on a scale Standard Error 1.82	-3.7 score on a scale Standard Error 1.57	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 8: LOCF; Weeks 10-24: participants with an assessment at given time point.

Administered every 2 visits, the 5-D Pruritus Scale evaluates pruritus in five domains: duration, degree, direction, disability and distribution. The scores from each domain are added together to obtain a total 5-D score ranging from 5 (no pruritus) to 25 (most severe pruritus). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Percent Change From Baseline in 5-D Pruritus Total Score Over Time Week 14	-35.1 percentage change Standard Error 7.28	-26.0 percentage change Standard Error 6.21	—	—	—	—
Phase 2a: Percent Change From Baseline in 5-D Pruritus Total Score Over Time Week 2	-26.8 percentage change Standard Error 3.83	-13.3 percentage change Standard Error 3.75	—	—	—	—
Phase 2a: Percent Change From Baseline in 5-D Pruritus Total Score Over Time Week 4	-31.8 percentage change Standard Error 4.83	-21.7 percentage change Standard Error 4.74	—	—	—	—
Phase 2a: Percent Change From Baseline in 5-D Pruritus Total Score Over Time Week 6	-34.2 percentage change Standard Error 4.65	-23.6 percentage change Standard Error 4.56	—	—	—	—
Phase 2a: Percent Change From Baseline in 5-D Pruritus Total Score Over Time Week 8	-36.8 percentage change Standard Error 5.04	-24.2 percentage change Standard Error 4.95	—	—	—	—
Phase 2a: Percent Change From Baseline in 5-D Pruritus Total Score Over Time Week 10	-36.2 percentage change Standard Error 4.69	-26.4 percentage change Standard Error 4.52	—	—	—	—
Phase 2a: Percent Change From Baseline in 5-D Pruritus Total Score Over Time Week 12	-33.7 percentage change Standard Error 4.90	-25.0 percentage change Standard Error 4.71	—	—	—	—
Phase 2a: Percent Change From Baseline in 5-D Pruritus Total Score Over Time Week 16	-35.0 percentage change Standard Error 4.66	-24.5 percentage change Standard Error 4.49	—	—	—	—
Phase 2a: Percent Change From Baseline in 5-D Pruritus Total Score Over Time Week 18	-30.5 percentage change Standard Error 7.71	-18.1 percentage change Standard Error 7.08	—	—	—	—
Phase 2a: Percent Change From Baseline in 5-D Pruritus Total Score Over Time Week 20	-34.1 percentage change Standard Error 8.05	-19.4 percentage change Standard Error 7.39	—	—	—	—
Phase 2a: Percent Change From Baseline in 5-D Pruritus Total Score Over Time Week 24	-36.6 percentage change Standard Error 8.92	-20.5 percentage change Standard Error 8.19	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period; Baseline through Week 16: LOCF; Weeks 17-24: participants with an assessment at given time point.

Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus).

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 2	26.1 percentage of participants Interval 10.2 to 48.4	7.7 percentage of participants Interval 0.9 to 25.1	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 3	39.1 percentage of participants Interval 19.7 to 61.5	11.5 percentage of participants Interval 2.4 to 30.2	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 4	52.2 percentage of participants Interval 30.6 to 73.2	23.1 percentage of participants Interval 9.0 to 43.6	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 5	52.2 percentage of participants Interval 30.6 to 73.2	23.1 percentage of participants Interval 9.0 to 43.6	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 7	52.2 percentage of participants Interval 30.6 to 73.2	34.6 percentage of participants Interval 17.2 to 55.7	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 8	52.2 percentage of participants Interval 30.6 to 73.2	30.8 percentage of participants Interval 14.3 to 51.8	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 9	52.2 percentage of participants Interval 30.6 to 73.2	30.8 percentage of participants Interval 14.3 to 51.8	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 10	47.8 percentage of participants Interval 26.8 to 69.4	34.6 percentage of participants Interval 17.2 to 55.7	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 11	47.8 percentage of participants Interval 26.8 to 69.4	34.6 percentage of participants Interval 17.2 to 55.7	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 12	47.8 percentage of participants Interval 26.8 to 69.4	34.6 percentage of participants Interval 17.2 to 55.7	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 13	52.2 percentage of participants Interval 30.6 to 73.2	26.9 percentage of participants Interval 11.6 to 47.8	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 14	52.2 percentage of participants Interval 30.6 to 73.2	30.8 percentage of participants Interval 14.3 to 51.8	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 15	52.2 percentage of participants Interval 30.6 to 73.2	30.8 percentage of participants Interval 14.3 to 51.8	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 16	52.2 percentage of participants Interval 30.6 to 73.2	42.3 percentage of participants Interval 23.4 to 63.1	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 17	36.4 percentage of participants Interval 10.9 to 69.2	41.7 percentage of participants Interval 15.2 to 72.3	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 18	50.0 percentage of participants Interval 18.7 to 81.3	33.3 percentage of participants Interval 9.9 to 65.1	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 19	60.0 percentage of participants Interval 26.2 to 87.8	33.3 percentage of participants Interval 9.9 to 65.1	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 20	60.0 percentage of participants Interval 26.2 to 87.8	41.7 percentage of participants Interval 15.2 to 72.3	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 22	50.0 percentage of participants Interval 18.7 to 81.3	25.0 percentage of participants Interval 5.5 to 57.2	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 23	60.0 percentage of participants Interval 26.2 to 87.8	33.3 percentage of participants Interval 9.9 to 65.1	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 24	60.0 percentage of participants Interval 26.2 to 87.8	41.7 percentage of participants Interval 15.2 to 72.3	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 6	52.2 percentage of participants Interval 30.6 to 73.2	26.9 percentage of participants Interval 11.6 to 47.8	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 21	60.0 percentage of participants Interval 26.2 to 87.8	50.0 percentage of participants Interval 21.1 to 78.9	—	—	—	—
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 1	17.4 percentage of participants Interval 5.0 to 38.8	7.7 percentage of participants Interval 0.9 to 25.1	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 8: LOCF; Weeks 9-24: participants with an assessment at given time point.

Participants rated intensity of their average sleeplessness over previous 3 days on 0-10 line scale (0=no sleeplessness, 10=worst imaginable sleeplessness).

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 1	-2.0 units on a scale Standard Error 0.54	-1.5 units on a scale Standard Error 0.42	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 2	-2.8 units on a scale Standard Error 0.58	-1.2 units on a scale Standard Error 0.50	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 3	-3.3 units on a scale Standard Error 0.63	-1.4 units on a scale Standard Error 0.61	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 4	-3.9 units on a scale Standard Error 0.71	-2.5 units on a scale Standard Error 0.57	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 5	-4.2 units on a scale Standard Error 0.71	-2.3 units on a scale Standard Error 0.59	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 6	-4.1 units on a scale Standard Error 0.73	-1.7 units on a scale Standard Error 0.61	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 7	-4.8 units on a scale Standard Error 0.73	-2.4 units on a scale Standard Error 0.61	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 8	-4.5 units on a scale Standard Error 0.68	-2.5 units on a scale Standard Error 0.53	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 9	-4.3 units on a scale Standard Error 1.16	-3.1 units on a scale Standard Error 0.74	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 10	-4.8 units on a scale Standard Error 0.74	-2.7 units on a scale Standard Error 0.57	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 11	-4.0 units on a scale Standard Error 1.23	-3.8 units on a scale Standard Error 0.74	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 12	-4.3 units on a scale Standard Error 0.64	-3.1 units on a scale Standard Error 0.55	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 13	-4.1 units on a scale Standard Error 1.27	-2.7 units on a scale Standard Error 0.82	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 14	-4.1 units on a scale Standard Error 1.24	-3.1 units on a scale Standard Error 0.85	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 15	-3.9 units on a scale Standard Error 1.21	-3.2 units on a scale Standard Error 0.90	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 16	-4.4 units on a scale Standard Error 0.70	-2.8 units on a scale Standard Error 0.59	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 18	-4.3 units on a scale Standard Error 1.20	-2.9 units on a scale Standard Error 0.81	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 20	-4.0 units on a scale Standard Error 1.27	-2.8 units on a scale Standard Error 0.97	—	—	—	—
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time Week 24	-4.3 units on a scale Standard Error 1.20	-2.6 units on a scale Standard Error 1.07	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 8: LOCF; Weeks 9-24: participants with an assessment at given time point.

Participants rated intensity of their average sleeplessness over previous 3 days on 0-10 line scale (0=no sleeplessness, 10=worst imaginable sleeplessness). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 1	-22.0 percentage change Standard Error 9.95	-13.1 percentage change Standard Error 9.66	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 2	-25.5 percentage change Standard Error 10.77	-2.2 percentage change Standard Error 10.46	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 3	-25.1 percentage change Standard Error 19.68	2.5 percentage change Standard Error 19.11	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 4	-44.9 percentage change Standard Error 9.02	-25.7 percentage change Standard Error 8.75	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 5	-48.5 percentage change Standard Error 9.02	-22.6 percentage change Standard Error 8.75	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 6	-40.1 percentage change Standard Error 16.09	-7.5 percentage change Standard Error 15.62	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 7	-53.8 percentage change Standard Error 9.25	-25.7 percentage change Standard Error 8.98	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 8	-56.3 percentage change Standard Error 7.72	-30.0 percentage change Standard Error 7.50	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 9	-45.1 percentage change Standard Error 12.13	-38.0 percentage change Standard Error 10.37	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 10	-56.9 percentage change Standard Error 8.25	-29.7 percentage change Standard Error 7.87	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 11	-50.6 percentage change Standard Error 13.53	-43.5 percentage change Standard Error 11.57	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 12	-50.4 percentage change Standard Error 7.85	-35.9 percentage change Standard Error 7.48	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 13	-54.2 percentage change Standard Error 14.30	-29.4 percentage change Standard Error 12.23	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 14	-50.0 percentage change Standard Error 13.52	-34.8 percentage change Standard Error 11.56	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 15	-44.2 percentage change Standard Error 16.22	-31.4 percentage change Standard Error 13.88	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 16	-52.4 percentage change Standard Error 9.11	-27.1 percentage change Standard Error 8.69	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 18	-54.3 percentage change Standard Error 12.93	-37.7 percentage change Standard Error 11.84	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 20	-42.9 percentage change Standard Error 15.26	-34.8 percentage change Standard Error 13.97	—	—	—	—
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time Week 24	-50.2 percentage change Standard Error 19.88	-24.6 percentage change Standard Error 18.20	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 16: LOCF; Weeks 17-24: participants with an assessment at given time point.

Participants rate difficulty falling asleep daily on Numerical Rating Scale (0=no difficulty, 10=extremely difficult).

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 9	-3.6 units on a scale Standard Error 0.72	-3.2 units on a scale Standard Error 0.43	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 10	-3.6 units on a scale Standard Error 0.68	-3.3 units on a scale Standard Error 0.39	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 11	-3.5 units on a scale Standard Error 0.69	-3.4 units on a scale Standard Error 0.44	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 12	-3.4 units on a scale Standard Error 0.69	-3.2 units on a scale Standard Error 0.41	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 13	-3.6 units on a scale Standard Error 0.68	-3.2 units on a scale Standard Error 0.44	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 14	-3.5 units on a scale Standard Error 0.69	-3.0 units on a scale Standard Error 0.44	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 15	-3.6 units on a scale Standard Error 0.70	-3.1 units on a scale Standard Error 0.44	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 16	-3.6 units on a scale Standard Error 0.69	-3.2 units on a scale Standard Error 0.45	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 17	-3.0 units on a scale Standard Error 1.14	-2.9 units on a scale Standard Error 0.74	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 18	-3.3 units on a scale Standard Error 1.16	-2.9 units on a scale Standard Error 0.78	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 19	-3.3 units on a scale Standard Error 1.16	-2.9 units on a scale Standard Error 0.76	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 20	-3.4 units on a scale Standard Error 1.16	-3.0 units on a scale Standard Error 0.83	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 21	-3.4 units on a scale Standard Error 1.18	-3.1 units on a scale Standard Error 0.83	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 22	-3.4 units on a scale Standard Error 1.17	-2.8 units on a scale Standard Error 0.78	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 23	-3.4 units on a scale Standard Error 1.18	-3.1 units on a scale Standard Error 0.83	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 24	-3.3 units on a scale Standard Error 1.18	-3.2 units on a scale Standard Error 0.84	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 1	-1.3 units on a scale Standard Error 0.37	-0.9 units on a scale Standard Error 0.30	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 2	-1.9 units on a scale Standard Error 0.46	-1.7 units on a scale Standard Error 0.34	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 3	-2.6 units on a scale Standard Error 0.54	-2.1 units on a scale Standard Error 0.41	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 4	-3.2 units on a scale Standard Error 0.63	-2.4 units on a scale Standard Error 0.43	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 5	-3.5 units on a scale Standard Error 0.67	-2.7 units on a scale Standard Error 0.42	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 6	-3.7 units on a scale Standard Error 0.70	-2.9 units on a scale Standard Error 0.40	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 7	-3.7 units on a scale Standard Error 0.73	-3.0 units on a scale Standard Error 0.43	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 8	-3.8 units on a scale Standard Error 0.74	-3.1 units on a scale Standard Error 0.45	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 16: LOCF; Weeks 17-24: participants with an assessment at given time point.

Participants rate difficulty falling asleep daily on Numerical Rating Scale (0=no difficulty, 10=extremely difficult). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 1	-17.2 percentage change Standard Error 5.20	-13.5 percentage change Standard Error 5.02	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 2	-24.2 percentage change Standard Error 5.78	-22.5 percentage change Standard Error 5.58	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 3	-31.6 percentage change Standard Error 6.15	-25.8 percentage change Standard Error 5.94	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 4	-39.2 percentage change Standard Error 6.98	-30.8 percentage change Standard Error 6.74	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 5	-43.1 percentage change Standard Error 7.58	-35.1 percentage change Standard Error 7.32	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 6	-44.0 percentage change Standard Error 7.87	-37.9 percentage change Standard Error 7.60	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 7	-44.2 percentage change Standard Error 8.04	-39.0 percentage change Standard Error 7.77	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 8	-45.4 percentage change Standard Error 8.13	-39.1 percentage change Standard Error 7.85	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 9	-42.1 percentage change Standard Error 8.10	-41.0 percentage change Standard Error 7.83	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 10	-43.3 percentage change Standard Error 7.53	-43.3 percentage change Standard Error 7.27	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 11	-41.2 percentage change Standard Error 7.78	-43.7 percentage change Standard Error 7.51	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 12	-40.8 percentage change Standard Error 7.72	-40.0 percentage change Standard Error 7.45	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 13	-44.5 percentage change Standard Error 7.26	-39.2 percentage change Standard Error 7.01	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 14	-45.3 percentage change Standard Error 7.33	-36.5 percentage change Standard Error 7.08	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 15	-46.2 percentage change Standard Error 7.30	-37.2 percentage change Standard Error 7.05	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 16	-46.3 percentage change Standard Error 7.51	-40.4 percentage change Standard Error 7.25	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 17	-41.5 percentage change Standard Error 12.68	-39.0 percentage change Standard Error 12.18	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 18	-44.3 percentage change Standard Error 12.62	-37.8 percentage change Standard Error 11.61	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 19	-44.7 percentage change Standard Error 12.66	-38.6 percentage change Standard Error 11.65	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 20	-44.0 percentage change Standard Error 12.84	-40.3 percentage change Standard Error 11.81	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 21	-46.1 percentage change Standard Error 13.37	-41.4 percentage change Standard Error 12.30	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 22	-44.1 percentage change Standard Error 12.68	-36.9 percentage change Standard Error 11.67	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 23	-43.9 percentage change Standard Error 13.02	-40.1 percentage change Standard Error 11.98	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time Week 24	-42.9 percentage change Standard Error 12.82	-41.5 percentage change Standard Error 11.80	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 16: LOCF; Weeks 17-24: participants with an assessment at given time point.

Participants rated daily sleep quality on Numerical Rating Scale (0=best possible sleep, 10=worst possible sleep).

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 1	-1.4 units on a scale Standard Error 0.38	-0.8 units on a scale Standard Error 0.26	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 2	-1.9 units on a scale Standard Error 0.45	-1.5 units on a scale Standard Error 0.33	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 3	-2.6 units on a scale Standard Error 0.55	-1.7 units on a scale Standard Error 0.35	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 4	-3.1 units on a scale Standard Error 0.67	-2.1 units on a scale Standard Error 0.36	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 5	-3.4 units on a scale Standard Error 0.68	-2.2 units on a scale Standard Error 0.39	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 6	-3.6 units on a scale Standard Error 0.67	-2.4 units on a scale Standard Error 0.39	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 7	-3.8 units on a scale Standard Error 0.71	-2.5 units on a scale Standard Error 0.41	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 8	-3.8 units on a scale Standard Error 0.71	-2.6 units on a scale Standard Error 0.42	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 9	-3.5 units on a scale Standard Error 0.67	-2.8 units on a scale Standard Error 0.41	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 10	-3.6 units on a scale Standard Error 0.66	-2.8 units on a scale Standard Error 0.43	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 11	-3.4 units on a scale Standard Error 0.68	-3.1 units on a scale Standard Error 0.42	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 12	-3.3 units on a scale Standard Error 0.67	-2.9 units on a scale Standard Error 0.41	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 13	-3.5 units on a scale Standard Error 0.70	-3.0 units on a scale Standard Error 0.43	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 14	-3.6 units on a scale Standard Error 0.71	-2.9 units on a scale Standard Error 0.46	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 15	-3.7 units on a scale Standard Error 0.71	-3.0 units on a scale Standard Error 0.46	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 16	-3.7 units on a scale Standard Error 0.68	-3.1 units on a scale Standard Error 0.45	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 17	-2.6 units on a scale Standard Error 1.10	-2.7 units on a scale Standard Error 0.79	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 18	-3.1 units on a scale Standard Error 1.16	-2.9 units on a scale Standard Error 0.79	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 19	-3.2 units on a scale Standard Error 1.17	-2.8 units on a scale Standard Error 0.77	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 20	-3.0 units on a scale Standard Error 1.14	-2.9 units on a scale Standard Error 0.84	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 21	-3.3 units on a scale Standard Error 1.18	-2.8 units on a scale Standard Error 0.86	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 22	-3.2 units on a scale Standard Error 1.17	-2.8 units on a scale Standard Error 0.78	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 23	-3.2 units on a scale Standard Error 1.18	-2.8 units on a scale Standard Error 0.84	—	—	—	—
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 24	-3.3 units on a scale Standard Error 1.16	-2.7 units on a scale Standard Error 0.78	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 16: LOCF; Weeks 17-24: participants with an assessment at given time point.

Participants rated daily sleep quality on Numerical Rating Scale (0=best possible sleep, 10=worst possible sleep). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 6	-42.8 percentage change Standard Error 7.23	-30.9 percentage change Standard Error 6.99	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 7	-45.3 percentage change Standard Error 7.40	-31.1 percentage change Standard Error 7.14	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 8	-46.1 percentage change Standard Error 7.52	-33.5 percentage change Standard Error 7.27	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 9	-42.0 percentage change Standard Error 7.52	-37.0 percentage change Standard Error 7.26	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 10	-42.8 percentage change Standard Error 7.38	-36.0 percentage change Standard Error 7.12	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 1	-11.0 percentage change Standard Error 5.98	-12.0 percentage change Standard Error 5.78	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 2	-21.9 percentage change Standard Error 5.59	-20.6 percentage change Standard Error 5.40	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 3	-29.6 percentage change Standard Error 5.94	-20.9 percentage change Standard Error 5.74	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 4	-33.6 percentage change Standard Error 7.04	-26.1 percentage change Standard Error 6.80	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 5	-39.6 percentage change Standard Error 7.24	-28.8 percentage change Standard Error 6.99	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 15	-44.0 percentage change Standard Error 7.94	-37.0 percentage change Standard Error 7.67	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 16	-45.7 percentage change Standard Error 7.71	-38.8 percentage change Standard Error 7.45	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 17	-33.2 percentage change Standard Error 12.43	-35.8 percentage change Standard Error 11.94	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 18	-38.8 percentage change Standard Error 12.59	-37.1 percentage change Standard Error 11.59	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 11	-41.5 percentage change Standard Error 7.49	-39.2 percentage change Standard Error 7.23	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 12	-40.1 percentage change Standard Error 7.37	-36.1 percentage change Standard Error 7.11	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 13	-40.9 percentage change Standard Error 7.66	-37.5 percentage change Standard Error 7.40	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 14	-40.3 percentage change Standard Error 8.40	-36.9 percentage change Standard Error 8.12	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 23	-41.2 percentage change Standard Error 13.42	-34.8 percentage change Standard Error 12.34	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 24	-42.4 percentage change Standard Error 13.00	-35.0 percentage change Standard Error 11.96	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 19	-41.4 percentage change Standard Error 12.76	-36.3 percentage change Standard Error 11.74	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 20	-37.3 percentage change Standard Error 12.79	-37.6 percentage change Standard Error 11.77	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 21	-42.3 percentage change Standard Error 13.40	-36.5 percentage change Standard Error 12.33	—	—	—	—
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time Week 22	-39.7 percentage change Standard Error 12.70	-35.9 percentage change Standard Error 11.68	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8, 12, 16, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 8: LOCF; Weeks 12-24: participants with an assessment at given time point.

QoL was assessed at designated visits and includes the DLQI whereby 0=no effect on quality of life; 30= extremely large effect on QoL.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Change From Baseline in Quality of Life (QoL) Measure Dermatology QoL Index (DLQI) Over Time Week 2	-6.7 score on a scale Standard Error 1.23	-2.8 score on a scale Standard Error 0.82	—	—	—	—
Phase 2a: Change From Baseline in Quality of Life (QoL) Measure Dermatology QoL Index (DLQI) Over Time Week 4	-8.3 score on a scale Standard Error 1.45	-4.5 score on a scale Standard Error 0.87	—	—	—	—
Phase 2a: Change From Baseline in Quality of Life (QoL) Measure Dermatology QoL Index (DLQI) Over Time Week 6	-8.9 score on a scale Standard Error 1.45	-6.1 score on a scale Standard Error 0.85	—	—	—	—
Phase 2a: Change From Baseline in Quality of Life (QoL) Measure Dermatology QoL Index (DLQI) Over Time Week 8	-9.4 score on a scale Standard Error 1.62	-6.3 score on a scale Standard Error 0.94	—	—	—	—
Phase 2a: Change From Baseline in Quality of Life (QoL) Measure Dermatology QoL Index (DLQI) Over Time Week 12	-6.8 score on a scale Standard Error 2.22	-7.3 score on a scale Standard Error 1.33	—	—	—	—
Phase 2a: Change From Baseline in Quality of Life (QoL) Measure Dermatology QoL Index (DLQI) Over Time Week 16	-8.1 score on a scale Standard Error 1.64	-6.9 score on a scale Standard Error 0.88	—	—	—	—
Phase 2a: Change From Baseline in Quality of Life (QoL) Measure Dermatology QoL Index (DLQI) Over Time Week 24	-7.0 score on a scale Standard Error 2.71	-7.3 score on a scale Standard Error 1.92	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8, 12, 16, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 8: LOCF; Weeks 12-24: participants with an assessment at given time point.

QoL was assessed at designated visits and includes the DLQI whereby 0=no effect on quality of life; 30= extremely large effect on QoL.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Percent Change From Baseline in QoL Measure DLQI Over Time Week 2	-40.0 percentage change Standard Error 6.26	-12.0 percentage change Standard Error 6.09	—	—	—	—
Phase 2a: Percent Change From Baseline in QoL Measure DLQI Over Time Week 4	-50.4 percentage change Standard Error 6.09	-29.1 percentage change Standard Error 5.93	—	—	—	—
Phase 2a: Percent Change From Baseline in QoL Measure DLQI Over Time Week 6	-54.1 percentage change Standard Error 6.34	-41.7 percentage change Standard Error 6.16	—	—	—	—
Phase 2a: Percent Change From Baseline in QoL Measure DLQI Over Time Week 8	-55.4 percentage change Standard Error 7.15	-43.0 percentage change Standard Error 6.95	—	—	—	—
Phase 2a: Percent Change From Baseline in QoL Measure DLQI Over Time Week 12	-46.9 percentage change Standard Error 10.33	-46.1 percentage change Standard Error 8.80	—	—	—	—
Phase 2a: Percent Change From Baseline in QoL Measure DLQI Over Time Week 16	-49.6 percentage change Standard Error 6.51	-45.2 percentage change Standard Error 6.23	—	—	—	—
Phase 2a: Percent Change From Baseline in QoL Measure DLQI Over Time Week 24	-54.6 percentage change Standard Error 12.86	-46.0 percentage change Standard Error 11.12	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8, 12, 16, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 8: LOCF; Weeks 12-24: participants with an assessment at given time point.

ItchyQoL focuses on impact of pruritus on daily activities and on the level of psychological stress. It contains 22 items. The frequency items are scored using a 5-point Likert scale ranging from "never" to "all the time". The bother items are scored from 1 (not bothered) to 5 (severely bothered). The recall period in ItchyQoL is the past week. The ItchyQoL total score is defined as the sum of all 22-items scores. Total scores can be classified as little (0-30), mild (31-50), moderate (51-80), and severe (81-110).

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Change From Baseline in QoL Measure Itchy Quality of Life (ItchyQoL) Over Time Week 2	-16.3 units on a scale Standard Error 3.18	-6.2 units on a scale Standard Error 1.08	—	—	—	—
Phase 2a: Change From Baseline in QoL Measure Itchy Quality of Life (ItchyQoL) Over Time Week 4	-25.3 units on a scale Standard Error 4.32	-11.0 units on a scale Standard Error 2.22	—	—	—	—
Phase 2a: Change From Baseline in QoL Measure Itchy Quality of Life (ItchyQoL) Over Time Week 6	-27.6 units on a scale Standard Error 4.60	-14.5 units on a scale Standard Error 2.50	—	—	—	—
Phase 2a: Change From Baseline in QoL Measure Itchy Quality of Life (ItchyQoL) Over Time Week 8	-30.0 units on a scale Standard Error 4.80	-16.0 units on a scale Standard Error 2.54	—	—	—	—
Phase 2a: Change From Baseline in QoL Measure Itchy Quality of Life (ItchyQoL) Over Time Week 12	-26.0 units on a scale Standard Error 7.57	-18.1 units on a scale Standard Error 3.51	—	—	—	—
Phase 2a: Change From Baseline in QoL Measure Itchy Quality of Life (ItchyQoL) Over Time Week 16	-29.6 units on a scale Standard Error 4.96	-15.8 units on a scale Standard Error 2.49	—	—	—	—
Phase 2a: Change From Baseline in QoL Measure Itchy Quality of Life (ItchyQoL) Over Time Week 24	-26.3 units on a scale Standard Error 8.44	-19.1 units on a scale Standard Error 5.15	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8, 12, 16, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 8: LOCF; Weeks 12-24: participants with an assessment at given time point.

ItchyQoL focuses on impact of pruritus on daily activities and on the level of psychological stress. It contains 22 items. The frequency items are scored using a 5-point Likert scale ranging from "never" to "all the time". The bother items are scored from 1 (not bothered) to 5 (severely bothered). The recall period in ItchyQoL is the past week. The ItchyQoL total score is defined as the sum of all 22-items scores. Total scores can be classified as little (0-30), mild (31-50), moderate (51-80), and severe (81-110). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Percent Change From Baseline in QoL Measure Itchy QoL Over Time Week 2	-16.4 percentage change Standard Error 2.60	-6.6 percentage change Standard Error 2.53	—	—	—	—
Phase 2a: Percent Change From Baseline in QoL Measure Itchy QoL Over Time Week 4	-27.5 percentage change Standard Error 3.78	-14.1 percentage change Standard Error 3.68	—	—	—	—
Phase 2a: Percent Change From Baseline in QoL Measure Itchy QoL Over Time Week 6	-29.6 percentage change Standard Error 3.99	-17.7 percentage change Standard Error 3.89	—	—	—	—
Phase 2a: Percent Change From Baseline in QoL Measure Itchy QoL Over Time Week 8	-32.6 percentage change Standard Error 4.25	-18.8 percentage change Standard Error 4.14	—	—	—	—
Phase 2a: Percent Change From Baseline in QoL Measure Itchy QoL Over Time Week 12	-29.7 percentage change Standard Error 6.26	-21.1 percentage change Standard Error 5.37	—	—	—	—
Phase 2a: Percent Change From Baseline in QoL Measure Itchy QoL Over Time Week 16	-32.2 percentage change Standard Error 4.26	-17.1 percentage change Standard Error 4.07	—	—	—	—
Phase 2a: Percent Change From Baseline in QoL Measure Itchy QoL Over Time Week 24	-29.8 percentage change Standard Error 7.56	-22.0 percentage change Standard Error 6.57	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 8: LOCF; Weeks 10-24: participants with an assessment at given time point.

PN-NAT, assessed at designated visits, is a novel exploratory tool for the evaluation of disease severity based on estimate of the number of nodules over the whole body, estimate of hardness of nodules over the whole body, estimate of extent of excoriation over the whole body, distribution of nodules, exact number of nodules in the representative area. The first three components (number of nodules over the whole body, estimate of hardness of nodules over the whole body, estimate of extent of excoriations over the whole body) were analyzed as secondary endpoints. For the Number of Nodules over the Whole Body score: 0=0 nodules; 1=1 to 9 nodules; 2=10 to 50 nodules; and 3=more than 50 nodules. A higher score indicates worse disease.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Change From Baseline in Prurigo Nodularis Nodule Assessment Tool (PN-NAT) Over Time: Number of Nodules Over the Whole Body Score Week 2	-0.2 score on a scale Standard Error 0.08	-0.1 score on a scale Standard Error 0.08	—	—	—	—
Phase 2a: Change From Baseline in Prurigo Nodularis Nodule Assessment Tool (PN-NAT) Over Time: Number of Nodules Over the Whole Body Score Week 4	-0.4 score on a scale Standard Error 0.14	-0.2 score on a scale Standard Error 0.08	—	—	—	—
Phase 2a: Change From Baseline in Prurigo Nodularis Nodule Assessment Tool (PN-NAT) Over Time: Number of Nodules Over the Whole Body Score Week 6	-0.5 score on a scale Standard Error 0.14	-0.2 score on a scale Standard Error 0.12	—	—	—	—
Phase 2a: Change From Baseline in Prurigo Nodularis Nodule Assessment Tool (PN-NAT) Over Time: Number of Nodules Over the Whole Body Score Week 8	-0.5 score on a scale Standard Error 0.16	-0.3 score on a scale Standard Error 0.11	—	—	—	—
Phase 2a: Change From Baseline in Prurigo Nodularis Nodule Assessment Tool (PN-NAT) Over Time: Number of Nodules Over the Whole Body Score Week 10	-0.5 score on a scale Standard Error 0.16	-0.3 score on a scale Standard Error 0.09	—	—	—	—
Phase 2a: Change From Baseline in Prurigo Nodularis Nodule Assessment Tool (PN-NAT) Over Time: Number of Nodules Over the Whole Body Score Week 12	-0.7 score on a scale Standard Error 0.18	-0.4 score on a scale Standard Error 0.11	—	—	—	—
Phase 2a: Change From Baseline in Prurigo Nodularis Nodule Assessment Tool (PN-NAT) Over Time: Number of Nodules Over the Whole Body Score Week 14	-0.9 score on a scale Standard Error 0.28	-0.5 score on a scale Standard Error 0.14	—	—	—	—
Phase 2a: Change From Baseline in Prurigo Nodularis Nodule Assessment Tool (PN-NAT) Over Time: Number of Nodules Over the Whole Body Score Week 16	-1.0 score on a scale Standard Error 0.19	-0.3 score on a scale Standard Error 0.09	—	—	—	—
Phase 2a: Change From Baseline in Prurigo Nodularis Nodule Assessment Tool (PN-NAT) Over Time: Number of Nodules Over the Whole Body Score Week 18	-0.9 score on a scale Standard Error 0.28	-0.5 score on a scale Standard Error 0.15	—	—	—	—
Phase 2a: Change From Baseline in Prurigo Nodularis Nodule Assessment Tool (PN-NAT) Over Time: Number of Nodules Over the Whole Body Score Week 20	-0.9 score on a scale Standard Error 0.28	-0.4 score on a scale Standard Error 0.15	—	—	—	—
Phase 2a: Change From Baseline in Prurigo Nodularis Nodule Assessment Tool (PN-NAT) Over Time: Number of Nodules Over the Whole Body Score Week 24	-0.9 score on a scale Standard Error 0.28	-0.5 score on a scale Standard Error 0.15	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 8: LOCF; Weeks 10-24: participants with an assessment at given time point.

PN-NAT, assessed at designated visits, is a novel exploratory tool for the evaluation of disease severity based on estimate of the number of nodules over the whole body, estimate of hardness of nodules over the whole body, estimate of extent of excoriation over the whole body, distribution of nodules, exact number of nodules in the representative area. The first three components (number of nodules over the whole body, estimate of hardness of nodules over the whole body, estimate of extent of excoriations over the whole body) were analyzed as secondary endpoints. For the Estimate of Hardness of Nodules Over the Whole Body score: 0=No nodules are hard; 1=Up to one-third of nodules are hard; 2=One-third to two-thirds of nodules are hard; and 3=More than two-thirds of nodules are hard. A higher score indicates worse disease.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Change From Baseline in PN-NAT Over Time: Estimate of Hardness of Nodules Over the Whole Body Week 2	-0.2 score on a scale Standard Error 0.12	-0.2 score on a scale Standard Error 0.12	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Estimate of Hardness of Nodules Over the Whole Body Week 4	-0.5 score on a scale Standard Error 0.19	-0.4 score on a scale Standard Error 0.15	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Estimate of Hardness of Nodules Over the Whole Body Week 6	-0.6 score on a scale Standard Error 0.23	-0.5 score on a scale Standard Error 0.16	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Estimate of Hardness of Nodules Over the Whole Body Week 8	-0.7 score on a scale Standard Error 0.23	-0.6 score on a scale Standard Error 0.17	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Estimate of Hardness of Nodules Over the Whole Body Week 10	-1.1 score on a scale Standard Error 0.23	-0.8 score on a scale Standard Error 0.17	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Estimate of Hardness of Nodules Over the Whole Body Week 12	-1.0 score on a scale Standard Error 0.22	-0.8 score on a scale Standard Error 0.19	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Estimate of Hardness of Nodules Over the Whole Body Week 14	-1.2 score on a scale Standard Error 0.39	-0.9 score on a scale Standard Error 0.25	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Estimate of Hardness of Nodules Over the Whole Body Week 16	-1.1 score on a scale Standard Error 0.24	-0.8 score on a scale Standard Error 0.20	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Estimate of Hardness of Nodules Over the Whole Body Week 18	-1.2 score on a scale Standard Error 0.42	-0.9 score on a scale Standard Error 0.26	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Estimate of Hardness of Nodules Over the Whole Body Week 20	-1.3 score on a scale Standard Error 0.45	-1.2 score on a scale Standard Error 0.24	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Estimate of Hardness of Nodules Over the Whole Body Week 24	-1.2 score on a scale Standard Error 0.39	-0.8 score on a scale Standard Error 0.18	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Baseline through Week 8: LOCF; Weeks 10-24: participants with an assessment at given time point.

PN-NAT, assessed at designated visits, is a novel exploratory tool for the evaluation of disease severity based on estimate of the number of nodules over the whole body, estimate of hardness of nodules over the whole body, estimate of extent of excoriation over the whole body, distribution of nodules, exact number of nodules in the representative area. The first three components (number of nodules over the whole body, estimate of hardness of nodules over the whole body, estimate of extent of excoriations over the whole body) were analyzed as secondary endpoints. For the Extent of Excoriations over the Whole Body score: 0=No nodules are excoriated; 1=Up to one-third of nodules are excoriated; 2=One-third to two-thirds of nodules are excoriated; and 3=More than two-thirds of nodules are excoriated. A higher score indicates worse disease.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Change From Baseline in PN-NAT Over Time: Extent of Excoriations Over the Whole Body Week 2	-0.2 score on a scale Standard Error 0.14	-0.2 score on a scale Standard Error 0.10	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Extent of Excoriations Over the Whole Body Week 4	-0.5 score on a scale Standard Error 0.23	-0.7 score on a scale Standard Error 0.16	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Extent of Excoriations Over the Whole Body Week 6	-0.6 score on a scale Standard Error 0.27	-0.7 score on a scale Standard Error 0.17	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Extent of Excoriations Over the Whole Body Week 8	-0.4 score on a scale Standard Error 0.26	-0.7 score on a scale Standard Error 0.17	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Extent of Excoriations Over the Whole Body Week 10	-0.7 score on a scale Standard Error 0.23	-0.8 score on a scale Standard Error 0.16	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Extent of Excoriations Over the Whole Body Week 12	-0.8 score on a scale Standard Error 0.23	-0.8 score on a scale Standard Error 0.16	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Extent of Excoriations Over the Whole Body Week 14	-1.0 score on a scale Standard Error 0.37	-1.0 score on a scale Standard Error 0.23	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Extent of Excoriations Over the Whole Body Week 16	-1.1 score on a scale Standard Error 0.19	-0.7 score on a scale Standard Error 0.16	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Extent of Excoriations Over the Whole Body Week 18	-1.0 score on a scale Standard Error 0.37	-1.0 score on a scale Standard Error 0.25	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Extent of Excoriations Over the Whole Body Week 20	-1.0 score on a scale Standard Error 0.33	-1.1 score on a scale Standard Error 0.26	—	—	—	—
Phase 2a: Change From Baseline in PN-NAT Over Time: Extent of Excoriations Over the Whole Body Week 24	-0.8 score on a scale Standard Error 0.29	-0.8 score on a scale Standard Error 0.27	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period; Baseline through Week 8: LOCF; Weeks 10-24: participants with an assessment at given time point.

PN-IGA, assessed at designated visits, is a novel exploratory tool for the overall investigator assessment of PN disease severity based on the presence/absence of nodules and the size of the nodules as defined by their elevation. The IGA utilizes a 5-point scale that ranges from 0 (clear) to 4 (severe disease).

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2a: Percentage of Participants With Improvement in Prurigo Nodularis Investigator Global Assessment (PN-IGA) by 2 Categories Over Time Week 6	43.5 percentage of participants Interval 23.2 to 65.5	11.5 percentage of participants Interval 2.4 to 30.2	—	—	—	—
Phase 2a: Percentage of Participants With Improvement in Prurigo Nodularis Investigator Global Assessment (PN-IGA) by 2 Categories Over Time Week 2	8.7 percentage of participants Interval 1.1 to 28.0	7.7 percentage of participants Interval 0.9 to 25.1	—	—	—	—
Phase 2a: Percentage of Participants With Improvement in Prurigo Nodularis Investigator Global Assessment (PN-IGA) by 2 Categories Over Time Week 4	13.0 percentage of participants Interval 2.8 to 33.6	7.7 percentage of participants Interval 0.9 to 25.1	—	—	—	—
Phase 2a: Percentage of Participants With Improvement in Prurigo Nodularis Investigator Global Assessment (PN-IGA) by 2 Categories Over Time Week 8	43.5 percentage of participants Interval 23.2 to 65.5	15.4 percentage of participants Interval 4.4 to 34.9	—	—	—	—
Phase 2a: Percentage of Participants With Improvement in Prurigo Nodularis Investigator Global Assessment (PN-IGA) by 2 Categories Over Time Week 10	40.9 percentage of participants Interval 20.7 to 63.6	19.2 percentage of participants Interval 6.6 to 39.4	—	—	—	—
Phase 2a: Percentage of Participants With Improvement in Prurigo Nodularis Investigator Global Assessment (PN-IGA) by 2 Categories Over Time Week 12	50.0 percentage of participants Interval 28.2 to 71.8	23.1 percentage of participants Interval 9.0 to 43.6	—	—	—	—
Phase 2a: Percentage of Participants With Improvement in Prurigo Nodularis Investigator Global Assessment (PN-IGA) by 2 Categories Over Time Week 14	60.0 percentage of participants Interval 26.2 to 87.8	35.7 percentage of participants Interval 12.8 to 64.9	—	—	—	—
Phase 2a: Percentage of Participants With Improvement in Prurigo Nodularis Investigator Global Assessment (PN-IGA) by 2 Categories Over Time Week 16	59.1 percentage of participants Interval 36.4 to 79.3	26.9 percentage of participants Interval 11.6 to 47.8	—	—	—	—
Phase 2a: Percentage of Participants With Improvement in Prurigo Nodularis Investigator Global Assessment (PN-IGA) by 2 Categories Over Time Week 18	60.0 percentage of participants Interval 26.2 to 87.8	16.7 percentage of participants Interval 2.1 to 48.4	—	—	—	—
Phase 2a: Percentage of Participants With Improvement in Prurigo Nodularis Investigator Global Assessment (PN-IGA) by 2 Categories Over Time Week 20	70.0 percentage of participants Interval 34.8 to 93.3	16.7 percentage of participants Interval 2.1 to 48.4	—	—	—	—
Phase 2a: Percentage of Participants With Improvement in Prurigo Nodularis Investigator Global Assessment (PN-IGA) by 2 Categories Over Time Week 24	50.0 percentage of participants Interval 18.7 to 81.3	8.3 percentage of participants Interval 0.2 to 38.5	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Non-responder imputation.

Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (0=no pruritus; 10=worst imaginable pruritus).

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS at Week 16	42.6 percentage of participants Interval 28.3 to 57.8	23.4 percentage of participants Interval 12.3 to 38.0	17.4 percentage of participants Interval 7.8 to 31.4	2.1 percentage of participants Interval 0.1 to 11.1	—	—

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Non-responder imputation.

Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (0=no pruritus; 10=worst imaginable pruritus).

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS at Week 16	66.0 percentage of participants Interval 50.7 to 79.1	61.7 percentage of participants Interval 46.4 to 75.5	29.8 percentage of participants Interval 17.3 to 44.9	16.7 percentage of participants Interval 7.5 to 30.2	—	—

SECONDARY outcome

Timeframe: Week 16

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period.

PN-IGA, assessed at designated visits, is a novel exploratory tool for the overall investigator assessment of PN disease severity based on the presence/absence of nodules and the size of the nodules as defined by their elevation. The IGA utilizes a 5-point scale that ranges from 0 (clear) to 4 (severe disease); 0 (clear) indicates no nodules and 1 (almost clear) indicates nodules are present, few of the nodules are moderately raised.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Percentage of Participants Achieving a Score of 0 or 1 in PN-IGA at Week 16	38.3 percentage of participants Interval 24.5 to 53.6	29.8 percentage of participants Interval 17.3 to 44.9	14.9 percentage of participants Interval 6.2 to 28.3	10.4 percentage of participants Interval 3.5 to 22.7	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1 through 52

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Participants with an assessment at given time point.

Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 6	-4.2 units on a scale Standard Error 0.35	-3.2 units on a scale Standard Error 0.34	-2.4 units on a scale Standard Error 0.34	-0.9 units on a scale Standard Error 0.33	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 7	-4.3 units on a scale Standard Error 0.36	-3.5 units on a scale Standard Error 0.35	-2.3 units on a scale Standard Error 0.36	-0.9 units on a scale Standard Error 0.35	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 8	-4.4 units on a scale Standard Error 0.37	-3.6 units on a scale Standard Error 0.36	-2.3 units on a scale Standard Error 0.37	-1.0 units on a scale Standard Error 0.36	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 10	-4.7 units on a scale Standard Error 0.39	-4.2 units on a scale Standard Error 0.39	-3.1 units on a scale Standard Error 0.39	-1.2 units on a scale Standard Error 0.39	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 11	-4.8 units on a scale Standard Error 0.40	-4.2 units on a scale Standard Error 0.40	-2.8 units on a scale Standard Error 0.40	-1.2 units on a scale Standard Error 0.40	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 12	-4.8 units on a scale Standard Error 0.41	-3.9 units on a scale Standard Error 0.41	-2.5 units on a scale Standard Error 0.40	-1.3 units on a scale Standard Error 0.40	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 13	-4.9 units on a scale Standard Error 0.41	-4.4 units on a scale Standard Error 0.41	-3.1 units on a scale Standard Error 0.41	-1.5 units on a scale Standard Error 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 14	-4.9 units on a scale Standard Error 0.42	-4.5 units on a scale Standard Error 0.42	-3.2 units on a scale Standard Error 0.41	-1.3 units on a scale Standard Error 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 15	-5.0 units on a scale Standard Error 0.41	-4.4 units on a scale Standard Error 0.41	-3.1 units on a scale Standard Error 0.41	-1.2 units on a scale Standard Error 0.40	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 16	-4.9 units on a scale Standard Error 0.41	-4.3 units on a scale Standard Error 0.42	-2.9 units on a scale Standard Error 0.41	-1.2 units on a scale Standard Error 0.40	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 17	-5.2 units on a scale Standard Error 0.43	-4.9 units on a scale Standard Error 0.44	-3.7 units on a scale Standard Error 0.43	-2.1 units on a scale Standard Error 0.42	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 18	-5.3 units on a scale Standard Error 0.43	-4.9 units on a scale Standard Error 0.44	-3.9 units on a scale Standard Error 0.42	-2.7 units on a scale Standard Error 0.42	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 19	-5.4 units on a scale Standard Error 0.43	-5.1 units on a scale Standard Error 0.44	-4.4 units on a scale Standard Error 0.43	-3.3 units on a scale Standard Error 0.43	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 20	-5.4 units on a scale Standard Error 0.43	-5.0 units on a scale Standard Error 0.45	-4.4 units on a scale Standard Error 0.43	-3.5 units on a scale Standard Error 0.43	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 21	-5.5 units on a scale Standard Error 0.44	-5.3 units on a scale Standard Error 0.46	-4.7 units on a scale Standard Error 0.43	-3.9 units on a scale Standard Error 0.43	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 22	-5.5 units on a scale Standard Error 0.45	-5.3 units on a scale Standard Error 0.46	-4.6 units on a scale Standard Error 0.44	-4.1 units on a scale Standard Error 0.43	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 23	-5.5 units on a scale Standard Error 0.46	-5.3 units on a scale Standard Error 0.47	-4.8 units on a scale Standard Error 0.44	-4.4 units on a scale Standard Error 0.44	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 24	-5.5 units on a scale Standard Error 0.46	-5.5 units on a scale Standard Error 0.46	-4.8 units on a scale Standard Error 0.44	-4.4 units on a scale Standard Error 0.44	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 25	-5.6 units on a scale Standard Error 0.45	-5.6 units on a scale Standard Error 0.46	-4.9 units on a scale Standard Error 0.44	-4.6 units on a scale Standard Error 0.44	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 30	-5.9 units on a scale Standard Error 0.44	-5.8 units on a scale Standard Error 0.45	-5.2 units on a scale Standard Error 0.44	-4.5 units on a scale Standard Error 0.42	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 31	-6.1 units on a scale Standard Error 0.44	-5.9 units on a scale Standard Error 0.45	-5.3 units on a scale Standard Error 0.43	-4.8 units on a scale Standard Error 0.42	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 32	-6.1 units on a scale Standard Error 0.44	-5.8 units on a scale Standard Error 0.44	-5.2 units on a scale Standard Error 0.43	-4.7 units on a scale Standard Error 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 33	-6.0 units on a scale Standard Error 0.44	-5.8 units on a scale Standard Error 0.44	-5.2 units on a scale Standard Error 0.42	-4.8 units on a scale Standard Error 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 34	-6.2 units on a scale Standard Error 0.44	-5.9 units on a scale Standard Error 0.44	-5.3 units on a scale Standard Error 0.43	-4.8 units on a scale Standard Error 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 35	-6.2 units on a scale Standard Error 0.45	-5.7 units on a scale Standard Error 0.44	-5.4 units on a scale Standard Error 0.43	-4.9 units on a scale Standard Error 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 36	-6.2 units on a scale Standard Error 0.45	-5.8 units on a scale Standard Error 0.45	-5.4 units on a scale Standard Error 0.43	-4.9 units on a scale Standard Error 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 37	-6.4 units on a scale Standard Error 0.45	-5.9 units on a scale Standard Error 0.45	-5.5 units on a scale Standard Error 0.43	-5.0 units on a scale Standard Error 0.42	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 38	-6.4 units on a scale Standard Error 0.45	-5.9 units on a scale Standard Error 0.44	-5.5 units on a scale Standard Error 0.42	-5.1 units on a scale Standard Error 0.42	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 39	-6.4 units on a scale Standard Error 0.44	-6.1 units on a scale Standard Error 0.44	-5.7 units on a scale Standard Error 0.42	-5.1 units on a scale Standard Error 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 40	-6.4 units on a scale Standard Error 0.44	-6.1 units on a scale Standard Error 0.44	-5.7 units on a scale Standard Error 0.42	-5.1 units on a scale Standard Error 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 26	-5.6 units on a scale Standard Error 0.45	-5.7 units on a scale Standard Error 0.46	-4.9 units on a scale Standard Error 0.44	-4.5 units on a scale Standard Error 0.43	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 27	-5.5 units on a scale Standard Error 0.44	-5.6 units on a scale Standard Error 0.46	-5.2 units on a scale Standard Error 0.44	-4.5 units on a scale Standard Error 0.42	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 28	-5.8 units on a scale Standard Error 0.45	-5.6 units on a scale Standard Error 0.46	-5.1 units on a scale Standard Error 0.45	-4.5 units on a scale Standard Error 0.43	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 29	-5.8 units on a scale Standard Error 0.43	-5.8 units on a scale Standard Error 0.45	-5.2 units on a scale Standard Error 0.43	-4.7 units on a scale Standard Error 0.42	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 49	-6.7 units on a scale Standard Error 0.44	-6.3 units on a scale Standard Error 0.46	-5.6 units on a scale Standard Error 0.46	-5.8 units on a scale Standard Error 0.42	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 50	-6.8 units on a scale Standard Error 0.45	-6.2 units on a scale Standard Error 0.46	-5.9 units on a scale Standard Error 0.46	-5.7 units on a scale Standard Error 0.44	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 51	-6.6 units on a scale Standard Error 0.44	-6.5 units on a scale Standard Error 0.48	-6.0 units on a scale Standard Error 0.44	-5.5 units on a scale Standard Error 0.43	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 52	-6.8 units on a scale Standard Error 0.45	-6.2 units on a scale Standard Error 0.49	-5.6 units on a scale Standard Error 0.45	-5.7 units on a scale Standard Error 0.43	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 41	-6.4 units on a scale Standard Error 0.43	-6.1 units on a scale Standard Error 0.44	-5.9 units on a scale Standard Error 0.42	-5.4 units on a scale Standard Error 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 42	-6.5 units on a scale Standard Error 0.42	-6.1 units on a scale Standard Error 0.43	-5.8 units on a scale Standard Error 0.41	-5.4 units on a scale Standard Error 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 43	-6.3 units on a scale Standard Error 0.43	-6.2 units on a scale Standard Error 0.43	-5.9 units on a scale Standard Error 0.42	-5.4 units on a scale Standard Error 0.40	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 44	-6.5 units on a scale Standard Error 0.43	-6.0 units on a scale Standard Error 0.44	-5.9 units on a scale Standard Error 0.42	-5.5 units on a scale Standard Error 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 45	-6.6 units on a scale Standard Error 0.41	-6.3 units on a scale Standard Error 0.43	-5.6 units on a scale Standard Error 0.41	-5.4 units on a scale Standard Error 0.40	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 46	-6.5 units on a scale Standard Error 0.42	-6.3 units on a scale Standard Error 0.43	-5.6 units on a scale Standard Error 0.42	-5.5 units on a scale Standard Error 0.40	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 47	-6.7 units on a scale Standard Error 0.43	-6.2 units on a scale Standard Error 0.44	-5.7 units on a scale Standard Error 0.43	-5.6 units on a scale Standard Error 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 48	-6.7 units on a scale Standard Error 0.42	-6.4 units on a scale Standard Error 0.43	-5.8 units on a scale Standard Error 0.42	-5.6 units on a scale Standard Error 0.40	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 4	-3.8 units on a scale Standard Error 0.33	-2.5 units on a scale Standard Error 0.33	-1.5 units on a scale Standard Error 0.33	-0.8 units on a scale Standard Error 0.33	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 5	-4.0 units on a scale Standard Error 0.33	-2.9 units on a scale Standard Error 0.33	-2.0 units on a scale Standard Error 0.33	-0.8 units on a scale Standard Error 0.33	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 1	-1.7 units on a scale Standard Error 0.21	-1.1 units on a scale Standard Error 0.21	-0.9 units on a scale Standard Error 0.21	-0.4 units on a scale Standard Error 0.21	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 2	-2.8 units on a scale Standard Error 0.30	-1.9 units on a scale Standard Error 0.29	-1.9 units on a scale Standard Error 0.30	-0.7 units on a scale Standard Error 0.29	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 3	-3.4 units on a scale Standard Error 0.32	-2.2 units on a scale Standard Error 0.32	-1.8 units on a scale Standard Error 0.32	-0.7 units on a scale Standard Error 0.31	—	—
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time Week 9	-4.6 units on a scale Standard Error 0.38	-3.9 units on a scale Standard Error 0.37	-2.7 units on a scale Standard Error 0.38	-1.1 units on a scale Standard Error 0.37	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1 through 52

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Participants with an assessment at given time point.

Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 1	-19.6 percentage change Standard Error 2.56	-12.5 percentage change Standard Error 2.56	-10.0 percentage change Standard Error 2.60	-5.1 percentage change Standard Error 2.53	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 2	-33.2 percentage change Standard Error 3.60	-21.9 percentage change Standard Error 3.57	-21.4 percentage change Standard Error 3.62	-7.9 percentage change Standard Error 3.52	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 3	-40.2 percentage change Standard Error 3.83	-25.4 percentage change Standard Error 3.83	-19.9 percentage change Standard Error 3.88	-8.2 percentage change Standard Error 3.78	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 4	-45.1 percentage change Standard Error 4.00	-29.7 percentage change Standard Error 3.96	-16.9 percentage change Standard Error 4.01	-9.1 percentage change Standard Error 3.91	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 5	-47.8 percentage change Standard Error 3.98	-34.2 percentage change Standard Error 3.94	-23.2 percentage change Standard Error 3.99	-9.6 percentage change Standard Error 3.89	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 6	-49.5 percentage change Standard Error 4.10	-38.2 percentage change Standard Error 4.02	-28.0 percentage change Standard Error 4.08	-10.5 percentage change Standard Error 3.97	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 7	-50.1 percentage change Standard Error 4.26	-41.3 percentage change Standard Error 4.18	-27.1 percentage change Standard Error 4.24	-11.0 percentage change Standard Error 4.17	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 8	-51.7 percentage change Standard Error 4.39	-42.1 percentage change Standard Error 4.30	-26.0 percentage change Standard Error 4.37	-11.7 percentage change Standard Error 4.30	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 9	-54.0 percentage change Standard Error 4.58	-45.9 percentage change Standard Error 4.48	-31.1 percentage change Standard Error 4.55	-13.3 percentage change Standard Error 4.48	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 10	-55.0 percentage change Standard Error 4.63	-49.4 percentage change Standard Error 4.59	-36.0 percentage change Standard Error 4.61	-14.3 percentage change Standard Error 4.58	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 12	-56.0 percentage change Standard Error 4.76	-46.8 percentage change Standard Error 4.78	-29.2 percentage change Standard Error 4.74	-14.6 percentage change Standard Error 4.71	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 13	-56.6 percentage change Standard Error 4.80	-51.6 percentage change Standard Error 4.82	-35.6 percentage change Standard Error 4.78	-17.9 percentage change Standard Error 4.74	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 14	-57.1 percentage change Standard Error 4.91	-52.9 percentage change Standard Error 4.93	-36.7 percentage change Standard Error 4.89	-15.3 percentage change Standard Error 4.85	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 15	-57.5 percentage change Standard Error 4.81	-52.1 percentage change Standard Error 4.83	-36.2 percentage change Standard Error 4.79	-14.9 percentage change Standard Error 4.75	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 16	-56.5 percentage change Standard Error 4.88	-51.2 percentage change Standard Error 4.90	-33.3 percentage change Standard Error 4.85	-14.8 percentage change Standard Error 4.77	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 11	-55.2 percentage change Standard Error 4.77	-49.5 percentage change Standard Error 4.79	-32.5 percentage change Standard Error 4.75	-14.3 percentage change Standard Error 4.72	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 17	-60.3 percentage change Standard Error 5.02	-57.2 percentage change Standard Error 5.14	-43.0 percentage change Standard Error 5.04	-25.1 percentage change Standard Error 4.98	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 18	-61.3 percentage change Standard Error 5.03	-57.9 percentage change Standard Error 5.20	-45.5 percentage change Standard Error 5.00	-31.4 percentage change Standard Error 4.99	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 19	-62.3 percentage change Standard Error 5.06	-59.9 percentage change Standard Error 5.24	-50.8 percentage change Standard Error 5.08	-38.1 percentage change Standard Error 5.02	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 20	-62.2 percentage change Standard Error 5.10	-58.2 percentage change Standard Error 5.27	-50.9 percentage change Standard Error 5.07	-40.6 percentage change Standard Error 5.06	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 21	-63.1 percentage change Standard Error 5.23	-62.2 percentage change Standard Error 5.37	-54.3 percentage change Standard Error 5.09	-45.7 percentage change Standard Error 5.07	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 22	-63.3 percentage change Standard Error 5.32	-62.3 percentage change Standard Error 5.40	-53.3 percentage change Standard Error 5.12	-47.4 percentage change Standard Error 5.10	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 23	-63.7 percentage change Standard Error 5.47	-62.7 percentage change Standard Error 5.49	-56.2 percentage change Standard Error 5.21	-50.6 percentage change Standard Error 5.18	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 24	-64.2 percentage change Standard Error 5.39	-64.3 percentage change Standard Error 7.41	-55.6 percentage change Standard Error 5.23	-50.5 percentage change Standard Error 5.16	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 25	-64.8 percentage change Standard Error 5.35	-65.0 percentage change Standard Error 5.37	-57.2 percentage change Standard Error 5.18	-53.0 percentage change Standard Error 5.13	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 26	-65.4 percentage change Standard Error 5.30	-66.2 percentage change Standard Error 5.44	-57.4 percentage change Standard Error 5.19	-51.8 percentage change Standard Error 5.08	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 27	-64.2 percentage change Standard Error 5.25	-65.3 percentage change Standard Error 5.46	-59.7 percentage change Standard Error 5.23	-51.9 percentage change Standard Error 5.03	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 28	-67.1 percentage change Standard Error 5.31	-65.0 percentage change Standard Error 5.40	-58.3 percentage change Standard Error 5.35	-51.6 percentage change Standard Error 5.03	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 29	-67.8 percentage change Standard Error 5.17	-68.4 percentage change Standard Error 5.30	-59.9 percentage change Standard Error 5.10	-54.1 percentage change Standard Error 4.95	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 30	-68.5 percentage change Standard Error 5.25	-67.5 percentage change Standard Error 5.39	-60.3 percentage change Standard Error 5.18	-52.7 percentage change Standard Error 4.98	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 31	-70.8 percentage change Standard Error 5.23	-68.5 percentage change Standard Error 5.30	-61.3 percentage change Standard Error 5.09	-55.1 percentage change Standard Error 4.95	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 32	-70.7 percentage change Standard Error 5.21	-67.9 percentage change Standard Error 5.21	-60.3 percentage change Standard Error 5.12	-54.9 percentage change Standard Error 4.88	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 33	-70.3 percentage change Standard Error 5.26	-68.3 percentage change Standard Error 5.19	-60.5 percentage change Standard Error 5.00	-56.1 percentage change Standard Error 4.85	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 34	-72.2 percentage change Standard Error 5.31	-68.9 percentage change Standard Error 5.30	-60.4 percentage change Standard Error 5.16	-55.5 percentage change Standard Error 4.96	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 35	-72.3 percentage change Standard Error 5.29	-67.2 percentage change Standard Error 5.23	-61.8 percentage change Standard Error 5.10	-56.5 percentage change Standard Error 4.90	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 36	-72.7 percentage change Standard Error 5.27	-68.2 percentage change Standard Error 5.29	-62.5 percentage change Standard Error 5.03	-56.3 percentage change Standard Error 4.88	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 37	-73.9 percentage change Standard Error 5.34	-68.8 percentage change Standard Error 5.30	-64.0 percentage change Standard Error 5.04	-58.0 percentage change Standard Error 4.96	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 38	-75.2 percentage change Standard Error 5.29	-69.5 percentage change Standard Error 5.25	-63.6 percentage change Standard Error 4.99	-59.1 percentage change Standard Error 4.97	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 39	-75.2 percentage change Standard Error 5.23	-71.0 percentage change Standard Error 5.27	-65.7 percentage change Standard Error 5.02	-59.3 percentage change Standard Error 4.87	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 40	-75.1 percentage change Standard Error 5.24	-71.4 percentage change Standard Error 5.28	-65.9 percentage change Standard Error 5.02	-59.6 percentage change Standard Error 4.87	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 41	-74.7 percentage change Standard Error 5.17	-70.8 percentage change Standard Error 5.21	-68.3 percentage change Standard Error 5.05	-62.3 percentage change Standard Error 4.88	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 42	-75.8 percentage change Standard Error 5.05	-71.2 percentage change Standard Error 5.15	-67.0 percentage change Standard Error 4.93	-62.7 percentage change Standard Error 4.82	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 43	-72.9 percentage change Standard Error 5.08	-73.0 percentage change Standard Error 5.06	-68.0 percentage change Standard Error 4.96	-62.1 percentage change Standard Error 4.78	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 44	-75.6 percentage change Standard Error 5.08	-70.5 percentage change Standard Error 5.15	-67.8 percentage change Standard Error 4.97	-63.4 percentage change Standard Error 4.80	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 45	-76.9 percentage change Standard Error 4.92	-73.7 percentage change Standard Error 5.05	-65.4 percentage change Standard Error 4.86	-62.8 percentage change Standard Error 4.71	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 46	-76.0 percentage change Standard Error 4.99	-74.0 percentage change Standard Error 5.02	-65.2 percentage change Standard Error 4.92	-64.3 percentage change Standard Error 4.76	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 47	-78.0 percentage change Standard Error 5.09	-72.4 percentage change Standard Error 5.13	-66.1 percentage change Standard Error 5.02	-65.2 percentage change Standard Error 4.86	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 48	-77.6 percentage change Standard Error 4.99	-74.4 percentage change Standard Error 5.09	-66.8 percentage change Standard Error 5.00	-64.9 percentage change Standard Error 4.71	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 49	-78.2 percentage change Standard Error 5.15	-73.8 percentage change Standard Error 5.40	-65.5 percentage change Standard Error 5.37	-67.3 percentage change Standard Error 4.92	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 50	-78.7 percentage change Standard Error 5.30	-72.8 percentage change Standard Error 5.40	-68.8 percentage change Standard Error 5.36	-66.8 percentage change Standard Error 5.16	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 51	-77.3 percentage change Standard Error 5.23	-75.7 percentage change Standard Error 5.66	-69.4 percentage change Standard Error 5.25	-64.6 percentage change Standard Error 5.08	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time Week 52	-79.1 percentage change Standard Error 5.27	-72.8 percentage change Standard Error 5.76	-64.8 percentage change Standard Error 5.33	-67.0 percentage change Standard Error 5.08	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1 through 52

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Non-responders imputation.

Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus).

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 44	51.1 percentage of participants Interval 35.8 to 66.3	58.1 percentage of participants Interval 42.1 to 73.0	58.7 percentage of participants Interval 43.2 to 73.0	50.0 percentage of participants Interval 34.9 to 65.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 45	55.6 percentage of participants Interval 40.0 to 70.4	65.1 percentage of participants Interval 49.1 to 79.0	50.0 percentage of participants Interval 34.9 to 65.1	52.2 percentage of participants Interval 36.9 to 67.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 46	55.6 percentage of participants Interval 40.0 to 70.4	60.5 percentage of participants Interval 44.4 to 75.0	47.8 percentage of participants Interval 32.9 to 63.1	52.2 percentage of participants Interval 36.9 to 67.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 47	55.6 percentage of participants Interval 40.0 to 70.4	60.5 percentage of participants Interval 44.4 to 75.0	47.8 percentage of participants Interval 32.9 to 63.1	54.3 percentage of participants Interval 39.0 to 69.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 48	55.6 percentage of participants Interval 40.0 to 70.4	58.1 percentage of participants Interval 42.1 to 73.0	58.7 percentage of participants Interval 43.2 to 73.0	56.5 percentage of participants Interval 41.1 to 71.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 49	60.0 percentage of participants Interval 44.3 to 74.3	55.8 percentage of participants Interval 39.9 to 70.9	52.2 percentage of participants Interval 36.9 to 67.1	58.7 percentage of participants Interval 43.2 to 73.0	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 50	60.0 percentage of participants Interval 44.3 to 74.3	55.8 percentage of participants Interval 39.9 to 70.9	54.3 percentage of participants Interval 39.0 to 69.1	54.3 percentage of participants Interval 39.0 to 69.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 51	57.8 percentage of participants Interval 42.2 to 72.3	53.5 percentage of participants Interval 37.7 to 68.8	54.3 percentage of participants Interval 39.0 to 69.1	52.2 percentage of participants Interval 36.9 to 67.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 52	60.0 percentage of participants Interval 44.3 to 74.3	46.5 percentage of participants Interval 31.2 to 62.3	47.8 percentage of participants Interval 32.9 to 63.1	56.5 percentage of participants Interval 41.1 to 71.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 5	29.8 percentage of participants Interval 17.3 to 44.9	10.6 percentage of participants Interval 3.5 to 23.1	8.7 percentage of participants Interval 2.4 to 20.8	2.1 percentage of participants Interval 0.1 to 11.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 6	27.7 percentage of participants Interval 15.6 to 42.6	17.0 percentage of participants Interval 7.6 to 30.8	8.7 percentage of participants Interval 2.4 to 20.8	0 percentage of participants Interval 0.0 to 7.4	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 7	29.8 percentage of participants Interval 17.3 to 44.9	21.3 percentage of participants Interval 10.7 to 35.7	10.9 percentage of participants Interval 3.6 to 23.6	0 percentage of participants Interval 0.0 to 7.4	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 10	38.3 percentage of participants Interval 24.5 to 53.6	23.4 percentage of participants Interval 12.3 to 38.0	19.6 percentage of participants Interval 9.4 to 33.9	6.3 percentage of participants Interval 1.3 to 17.2	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 11	40.4 percentage of participants Interval 26.4 to 55.7	25.5 percentage of participants Interval 13.9 to 40.3	13.0 percentage of participants Interval 4.9 to 26.3	4.2 percentage of participants Interval 0.5 to 14.3	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 12	36.2 percentage of participants Interval 22.7 to 51.5	21.3 percentage of participants Interval 10.7 to 35.7	10.9 percentage of participants Interval 3.6 to 23.6	6.3 percentage of participants Interval 1.3 to 17.2	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 16	42.6 percentage of participants Interval 28.3 to 57.8	23.4 percentage of participants Interval 12.3 to 38.0	17.4 percentage of participants Interval 7.8 to 31.4	2.1 percentage of participants Interval 0.1 to 11.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 17	51.1 percentage of participants Interval 35.8 to 66.3	34.9 percentage of participants Interval 21.0 to 50.9	21.7 percentage of participants Interval 10.9 to 36.4	13.0 percentage of participants Interval 4.9 to 26.3	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 18	53.3 percentage of participants Interval 37.9 to 68.3	37.2 percentage of participants Interval 23.0 to 53.3	28.3 percentage of participants Interval 16.0 to 43.5	17.4 percentage of participants Interval 7.8 to 31.4	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 19	53.3 percentage of participants Interval 37.9 to 68.3	41.9 percentage of participants Interval 27.0 to 57.9	39.1 percentage of participants Interval 25.1 to 54.6	23.9 percentage of participants Interval 12.6 to 38.8	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 4	27.7 percentage of participants Interval 15.6 to 42.6	10.6 percentage of participants Interval 3.5 to 23.1	6.5 percentage of participants Interval 1.4 to 17.9	0 percentage of participants Interval 0.0 to 7.4	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 20	55.6 percentage of participants Interval 40.0 to 70.4	37.2 percentage of participants Interval 23.0 to 53.3	34.8 percentage of participants Interval 21.4 to 50.2	32.6 percentage of participants Interval 19.5 to 48.0	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 21	55.6 percentage of participants Interval 40.0 to 70.4	55.8 percentage of participants Interval 39.9 to 70.9	43.5 percentage of participants Interval 28.9 to 58.9	32.6 percentage of participants Interval 19.5 to 48.0	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 22	51.1 percentage of participants Interval 35.8 to 66.3	53.5 percentage of participants Interval 37.7 to 68.8	37.0 percentage of participants Interval 23.2 to 52.5	32.6 percentage of participants Interval 19.5 to 48.0	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 24	46.7 percentage of participants Interval 31.7 to 62.1	58.1 percentage of participants Interval 42.1 to 73.0	47.8 percentage of participants Interval 32.9 to 63.1	43.5 percentage of participants Interval 28.9 to 58.9	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 23	46.7 percentage of participants Interval 31.7 to 62.1	51.2 percentage of participants Interval 35.5 to 66.7	43.5 percentage of participants Interval 28.9 to 58.9	43.5 percentage of participants Interval 28.9 to 58.9	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 31	60.0 percentage of participants Interval 44.3 to 74.3	55.8 percentage of participants Interval 39.9 to 70.9	50.0 percentage of participants Interval 34.9 to 65.1	47.8 percentage of participants Interval 32.9 to 63.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 25	48.9 percentage of participants Interval 33.7 to 64.2	53.5 percentage of participants Interval 37.7 to 68.8	45.7 percentage of participants Interval 30.9 to 61.0	47.8 percentage of participants Interval 32.9 to 63.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 26	48.9 percentage of participants Interval 33.7 to 64.2	55.8 percentage of participants Interval 39.9 to 70.9	45.7 percentage of participants Interval 30.9 to 61.0	45.7 percentage of participants Interval 30.9 to 61.0	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 27	55.6 percentage of participants Interval 40.0 to 70.4	55.8 percentage of participants Interval 39.9 to 70.9	43.5 percentage of participants Interval 28.9 to 58.9	47.8 percentage of participants Interval 32.9 to 63.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 28	53.3 percentage of participants Interval 37.9 to 68.3	55.8 percentage of participants Interval 39.9 to 70.9	41.3 percentage of participants Interval 27.0 to 56.8	45.7 percentage of participants Interval 30.9 to 61.0	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 29	55.6 percentage of participants Interval 40.0 to 70.4	58.1 percentage of participants Interval 42.1 to 73.0	47.8 percentage of participants Interval 32.9 to 63.1	47.8 percentage of participants Interval 32.9 to 63.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 30	57.8 percentage of participants Interval 42.2 to 72.3	55.8 percentage of participants Interval 39.9 to 70.9	45.7 percentage of participants Interval 30.9 to 61.0	47.8 percentage of participants Interval 32.9 to 63.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 32	53.3 percentage of participants Interval 37.9 to 68.3	53.5 percentage of participants Interval 37.7 to 68.8	45.7 percentage of participants Interval 30.9 to 61.0	52.2 percentage of participants Interval 36.9 to 67.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 33	57.8 percentage of participants Interval 42.2 to 72.3	62.8 percentage of participants Interval 46.7 to 77.0	50.0 percentage of participants Interval 34.9 to 65.1	50.0 percentage of participants Interval 34.9 to 65.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 34	60.0 percentage of participants Interval 44.3 to 74.3	58.1 percentage of participants Interval 42.1 to 73.0	47.8 percentage of participants Interval 32.9 to 63.1	50.0 percentage of participants Interval 34.9 to 65.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 35	57.8 percentage of participants Interval 42.2 to 72.3	55.8 percentage of participants Interval 39.9 to 70.9	50.0 percentage of participants Interval 34.9 to 65.1	50.0 percentage of participants Interval 34.9 to 65.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 36	57.8 percentage of participants Interval 42.2 to 72.3	55.8 percentage of participants Interval 39.9 to 70.9	58.7 percentage of participants Interval 43.2 to 73.0	50.0 percentage of participants Interval 34.9 to 65.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 37	55.6 percentage of participants Interval 40.0 to 70.4	58.1 percentage of participants Interval 42.1 to 73.0	56.5 percentage of participants Interval 41.1 to 71.1	47.8 percentage of participants Interval 32.9 to 63.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 38	55.6 percentage of participants Interval 40.0 to 70.4	60.5 percentage of participants Interval 44.4 to 75.0	54.3 percentage of participants Interval 39.0 to 69.1	50.0 percentage of participants Interval 34.9 to 65.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 39	60.0 percentage of participants Interval 44.3 to 74.3	60.5 percentage of participants Interval 44.4 to 75.0	60.9 percentage of participants Interval 45.4 to 74.9	52.2 percentage of participants Interval 36.9 to 67.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 40	51.1 percentage of participants Interval 35.8 to 66.3	58.1 percentage of participants Interval 42.1 to 73.0	60.9 percentage of participants Interval 45.4 to 74.9	52.2 percentage of participants Interval 36.9 to 67.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 41	55.6 percentage of participants Interval 40.0 to 70.4	58.1 percentage of participants Interval 42.1 to 73.0	56.5 percentage of participants Interval 41.1 to 71.1	54.3 percentage of participants Interval 39.0 to 69.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 42	53.3 percentage of participants Interval 37.9 to 68.3	60.5 percentage of participants Interval 44.4 to 75.0	58.7 percentage of participants Interval 43.2 to 73.0	54.3 percentage of participants Interval 39.0 to 69.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 43	46.7 percentage of participants Interval 31.7 to 62.1	62.8 percentage of participants Interval 46.7 to 77.0	54.3 percentage of participants Interval 39.0 to 69.1	52.2 percentage of participants Interval 36.9 to 67.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 1	4.3 percentage of participants Interval 0.5 to 14.5	0 percentage of participants Interval 0.0 to 7.5	2.2 percentage of participants Interval 0.1 to 11.5	2.1 percentage of participants Interval 0.1 to 11.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 2	12.8 percentage of participants Interval 4.8 to 25.7	4.3 percentage of participants Interval 0.5 to 14.5	8.7 percentage of participants Interval 2.4 to 20.8	2.1 percentage of participants Interval 0.1 to 11.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 3	21.3 percentage of participants Interval 10.7 to 35.7	2.1 percentage of participants Interval 0.1 to 11.3	8.7 percentage of participants Interval 2.4 to 20.8	2.1 percentage of participants Interval 0.1 to 11.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 8	34.0 percentage of participants Interval 20.9 to 49.3	19.1 percentage of participants Interval 9.1 to 33.3	6.5 percentage of participants Interval 1.4 to 17.9	2.1 percentage of participants Interval 0.1 to 11.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 9	31.9 percentage of participants Interval 19.1 to 47.1	21.3 percentage of participants Interval 10.7 to 35.7	15.2 percentage of participants Interval 6.3 to 28.9	4.2 percentage of participants Interval 0.5 to 14.3	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 13	36.2 percentage of participants Interval 22.7 to 51.5	31.9 percentage of participants Interval 19.1 to 47.1	17.4 percentage of participants Interval 7.8 to 31.4	6.3 percentage of participants Interval 1.3 to 17.2	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 14	42.6 percentage of participants Interval 28.3 to 57.8	29.8 percentage of participants Interval 17.3 to 44.9	19.6 percentage of participants Interval 9.4 to 33.9	8.3 percentage of participants Interval 2.3 to 20.0	—	—
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 15	42.6 percentage of participants Interval 28.3 to 57.8	27.7 percentage of participants Interval 15.6 to 42.6	17.4 percentage of participants Interval 7.8 to 31.4	6.3 percentage of participants Interval 1.3 to 17.2	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1 through 52

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Non-responders imputation.

Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus).

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 1	10.6 percentage of participants Interval 3.5 to 23.1	4.3 percentage of participants Interval 0.5 to 14.5	4.3 percentage of participants Interval 0.5 to 14.5	2.1 percentage of participants Interval 0.1 to 11.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 2	25.5 percentage of participants Interval 13.9 to 40.3	17.0 percentage of participants Interval 7.6 to 30.8	17.0 percentage of participants Interval 7.6 to 30.8	4.2 percentage of participants Interval 0.5 to 14.3	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 3	44.7 percentage of participants Interval 30.2 to 59.9	17.0 percentage of participants Interval 7.6 to 30.8	17.0 percentage of participants Interval 7.6 to 30.8	4.2 percentage of participants Interval 0.5 to 14.3	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 4	53.2 percentage of participants Interval 38.1 to 67.9	25.5 percentage of participants Interval 13.9 to 40.3	10.6 percentage of participants Interval 3.5 to 23.1	6.3 percentage of participants Interval 1.3 to 17.2	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 5	53.2 percentage of participants Interval 38.1 to 67.9	29.8 percentage of participants Interval 17.3 to 44.9	21.3 percentage of participants Interval 10.7 to 35.7	2.1 percentage of participants Interval 0.1 to 11.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 6	53.2 percentage of participants Interval 38.1 to 67.9	38.3 percentage of participants Interval 24.5 to 53.6	27.7 percentage of participants Interval 15.6 to 42.6	6.3 percentage of participants Interval 1.3 to 17.2	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 9	59.6 percentage of participants Interval 44.3 to 73.6	51.1 percentage of participants Interval 36.1 to 65.9	36.2 percentage of participants Interval 22.7 to 51.5	8.3 percentage of participants Interval 2.3 to 20.0	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 10	66.0 percentage of participants Interval 50.7 to 79.1	59.6 percentage of participants Interval 44.3 to 73.6	38.3 percentage of participants Interval 24.5 to 53.6	12.5 percentage of participants Interval 4.7 to 25.2	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 11	63.8 percentage of participants Interval 48.5 to 77.3	55.3 percentage of participants Interval 40.1 to 69.8	31.9 percentage of participants Interval 19.1 to 47.1	16.7 percentage of participants Interval 7.5 to 30.2	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 12	61.7 percentage of participants Interval 46.4 to 75.5	57.4 percentage of participants Interval 42.2 to 71.7	29.8 percentage of participants Interval 17.3 to 44.9	16.7 percentage of participants Interval 7.5 to 30.2	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 13	63.8 percentage of participants Interval 48.5 to 77.3	59.6 percentage of participants Interval 44.3 to 73.6	36.2 percentage of participants Interval 22.7 to 51.5	14.6 percentage of participants Interval 6.1 to 27.8	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 14	68.1 percentage of participants Interval 52.9 to 80.9	63.8 percentage of participants Interval 48.5 to 77.3	38.3 percentage of participants Interval 24.5 to 53.6	16.7 percentage of participants Interval 7.5 to 30.2	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 15	66.0 percentage of participants Interval 50.7 to 79.1	59.6 percentage of participants Interval 44.3 to 73.6	36.2 percentage of participants Interval 22.7 to 51.5	14.6 percentage of participants Interval 6.1 to 27.8	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 16	66.0 percentage of participants Interval 50.7 to 79.1	61.7 percentage of participants Interval 46.4 to 75.5	29.8 percentage of participants Interval 17.3 to 44.9	16.7 percentage of participants Interval 7.5 to 30.2	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 17	68.9 percentage of participants Interval 53.4 to 81.8	72.1 percentage of participants Interval 56.3 to 84.7	48.9 percentage of participants Interval 34.1 to 63.9	21.7 percentage of participants Interval 10.9 to 36.4	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 18	66.7 percentage of participants Interval 51.0 to 80.0	72.1 percentage of participants Interval 56.3 to 84.7	46.8 percentage of participants Interval 32.1 to 61.9	32.6 percentage of participants Interval 19.5 to 48.0	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 7	57.4 percentage of participants Interval 42.2 to 71.7	38.3 percentage of participants Interval 24.5 to 53.6	27.7 percentage of participants Interval 15.6 to 42.6	8.3 percentage of participants Interval 2.3 to 20.0	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 8	57.4 percentage of participants Interval 42.2 to 71.7	36.2 percentage of participants Interval 22.7 to 51.5	27.7 percentage of participants Interval 15.6 to 42.6	8.3 percentage of participants Interval 2.3 to 20.0	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 36	71.1 percentage of participants Interval 55.7 to 83.6	69.8 percentage of participants Interval 53.9 to 82.8	72.3 percentage of participants Interval 57.4 to 84.4	65.2 percentage of participants Interval 49.8 to 78.6	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 37	71.1 percentage of participants Interval 55.7 to 83.6	74.4 percentage of participants Interval 58.8 to 86.5	72.3 percentage of participants Interval 57.4 to 84.4	69.6 percentage of participants Interval 54.2 to 82.3	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 38	75.6 percentage of participants Interval 60.5 to 87.1	72.1 percentage of participants Interval 56.3 to 84.7	72.3 percentage of participants Interval 57.4 to 84.4	69.6 percentage of participants Interval 54.2 to 82.3	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 39	71.1 percentage of participants Interval 55.7 to 83.6	72.1 percentage of participants Interval 56.3 to 84.7	68.1 percentage of participants Interval 52.9 to 80.9	71.7 percentage of participants Interval 56.5 to 84.0	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 40	73.3 percentage of participants Interval 58.1 to 85.4	69.8 percentage of participants Interval 53.9 to 82.8	68.1 percentage of participants Interval 52.9 to 80.9	69.6 percentage of participants Interval 54.2 to 82.3	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 41	71.1 percentage of participants Interval 55.7 to 83.6	72.1 percentage of participants Interval 56.3 to 84.7	68.1 percentage of participants Interval 52.9 to 80.9	71.7 percentage of participants Interval 56.5 to 84.0	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 42	71.1 percentage of participants Interval 55.7 to 83.6	72.1 percentage of participants Interval 56.3 to 84.7	68.1 percentage of participants Interval 52.9 to 80.9	71.7 percentage of participants Interval 56.5 to 84.0	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 43	71.1 percentage of participants Interval 55.7 to 83.6	74.4 percentage of participants Interval 58.8 to 86.5	66.0 percentage of participants Interval 50.7 to 79.1	69.6 percentage of participants Interval 54.2 to 82.3	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 44	73.3 percentage of participants Interval 58.1 to 85.4	69.8 percentage of participants Interval 53.9 to 82.8	66.0 percentage of participants Interval 50.7 to 79.1	73.9 percentage of participants Interval 58.9 to 85.7	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 45	75.6 percentage of participants Interval 60.5 to 87.1	69.8 percentage of participants Interval 53.9 to 82.8	66.0 percentage of participants Interval 50.7 to 79.1	69.6 percentage of participants Interval 54.2 to 82.3	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 46	75.6 percentage of participants Interval 60.5 to 87.1	76.7 percentage of participants Interval 61.4 to 88.2	68.1 percentage of participants Interval 52.9 to 80.9	73.9 percentage of participants Interval 58.9 to 85.7	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 47	75.6 percentage of participants Interval 60.5 to 87.1	72.1 percentage of participants Interval 56.3 to 84.7	66.0 percentage of participants Interval 50.7 to 79.1	73.9 percentage of participants Interval 58.9 to 85.7	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 48	75.6 percentage of participants Interval 60.5 to 87.1	69.8 percentage of participants Interval 53.9 to 82.8	63.8 percentage of participants Interval 48.5 to 77.3	76.1 percentage of participants Interval 61.2 to 87.4	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 49	75.6 percentage of participants Interval 60.5 to 87.1	67.4 percentage of participants Interval 51.5 to 80.9	59.6 percentage of participants Interval 44.3 to 73.6	73.9 percentage of participants Interval 58.9 to 85.7	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 50	71.1 percentage of participants Interval 55.7 to 83.6	65.1 percentage of participants Interval 49.1 to 79.0	61.7 percentage of participants Interval 46.4 to 75.5	67.4 percentage of participants Interval 52.0 to 80.5	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 51	71.1 percentage of participants Interval 55.7 to 83.6	60.5 percentage of participants Interval 44.4 to 75.0	61.7 percentage of participants Interval 46.4 to 75.5	65.2 percentage of participants Interval 49.8 to 78.6	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 52	71.1 percentage of participants Interval 55.7 to 83.6	55.8 percentage of participants Interval 39.9 to 70.9	57.4 percentage of participants Interval 42.2 to 71.7	69.6 percentage of participants Interval 54.2 to 82.3	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 19	71.1 percentage of participants Interval 55.7 to 83.6	72.1 percentage of participants Interval 56.3 to 84.7	55.3 percentage of participants Interval 40.1 to 69.8	43.5 percentage of participants Interval 28.9 to 58.9	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 20	71.1 percentage of participants Interval 55.7 to 83.6	67.4 percentage of participants Interval 51.5 to 80.9	57.4 percentage of participants Interval 42.2 to 71.7	47.8 percentage of participants Interval 32.9 to 63.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 21	68.9 percentage of participants Interval 53.4 to 81.8	72.1 percentage of participants Interval 56.3 to 84.7	68.1 percentage of participants Interval 52.9 to 80.9	52.2 percentage of participants Interval 36.9 to 67.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 23	64.4 percentage of participants Interval 48.8 to 78.1	76.7 percentage of participants Interval 61.4 to 88.2	66.0 percentage of participants Interval 50.7 to 79.1	56.5 percentage of participants Interval 41.1 to 71.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 24	68.9 percentage of participants Interval 53.4 to 81.8	72.1 percentage of participants Interval 56.3 to 84.7	68.1 percentage of participants Interval 52.9 to 80.9	54.3 percentage of participants Interval 39.0 to 69.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 25	64.4 percentage of participants Interval 48.8 to 78.1	74.4 percentage of participants Interval 58.8 to 86.5	66.0 percentage of participants Interval 50.7 to 79.1	56.5 percentage of participants Interval 41.1 to 71.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 26	66.7 percentage of participants Interval 51.0 to 80.0	72.1 percentage of participants Interval 56.3 to 84.7	70.2 percentage of participants Interval 55.1 to 82.7	56.5 percentage of participants Interval 41.1 to 71.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 27	66.7 percentage of participants Interval 51.0 to 80.0	72.1 percentage of participants Interval 56.3 to 84.7	68.1 percentage of participants Interval 52.9 to 80.9	60.9 percentage of participants Interval 45.4 to 74.9	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 22	66.7 percentage of participants Interval 51.0 to 80.0	72.1 percentage of participants Interval 56.3 to 84.7	61.7 percentage of participants Interval 46.4 to 75.5	54.3 percentage of participants Interval 39.0 to 69.1	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 32	68.9 percentage of participants Interval 53.4 to 81.8	74.4 percentage of participants Interval 58.8 to 86.5	61.7 percentage of participants Interval 46.4 to 75.5	63.0 percentage of participants Interval 47.5 to 76.8	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 33	66.7 percentage of participants Interval 51.0 to 80.0	76.7 percentage of participants Interval 61.4 to 88.2	66.0 percentage of participants Interval 50.7 to 79.1	67.4 percentage of participants Interval 52.0 to 80.5	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 34	71.1 percentage of participants Interval 55.7 to 83.6	72.1 percentage of participants Interval 56.3 to 84.7	66.0 percentage of participants Interval 50.7 to 79.1	63.0 percentage of participants Interval 47.5 to 76.8	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 35	71.1 percentage of participants Interval 55.7 to 83.6	67.4 percentage of participants Interval 51.5 to 80.9	68.1 percentage of participants Interval 52.9 to 80.9	67.4 percentage of participants Interval 52.0 to 80.5	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 29	68.9 percentage of participants Interval 53.4 to 81.8	72.1 percentage of participants Interval 56.3 to 84.7	68.1 percentage of participants Interval 52.9 to 80.9	65.2 percentage of participants Interval 49.8 to 78.6	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 30	68.9 percentage of participants Interval 53.4 to 81.8	72.1 percentage of participants Interval 56.3 to 84.7	68.1 percentage of participants Interval 52.9 to 80.9	63.0 percentage of participants Interval 47.5 to 76.8	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 31	71.1 percentage of participants Interval 55.7 to 83.6	72.1 percentage of participants Interval 56.3 to 84.7	66.0 percentage of participants Interval 50.7 to 79.1	63.0 percentage of participants Interval 47.5 to 76.8	—	—
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time Week 28	68.9 percentage of participants Interval 53.4 to 81.8	72.1 percentage of participants Interval 56.3 to 84.7	61.7 percentage of participants Interval 46.4 to 75.5	60.9 percentage of participants Interval 45.4 to 74.9	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Non-responders imputation.

PN-IGA is a novel exploratory tool for the overall investigator assessment of PN disease severity based on the presence/absence of nodules and the size of the nodules as defined by their elevation. The IGA utilizes a 5-point scale that ranges from 0 (clear) to 4 (severe disease); 0 (clear) indicates no nodules and 1 (almost clear) indicates nodules are present, few of the nodules are moderately raised.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Percentage of Participants Achieving 0 or 1 in PN-IGA Over Time Week 2	6.4 percentage of participants Interval 1.3 to 17.5	0.0 percentage of participants Interval 0.0 to 7.5	2.1 percentage of participants Interval 0.1 to 11.3	0 percentage of participants Interval 0.0 to 7.4	—	—
Phase 2b: Percentage of Participants Achieving 0 or 1 in PN-IGA Over Time Week 4	6.4 percentage of participants Interval 1.3 to 17.5	4.3 percentage of participants Interval 0.5 to 14.5	4.3 percentage of participants Interval 0.5 to 14.5	2.1 percentage of participants Interval 0.1 to 11.1	—	—
Phase 2b: Percentage of Participants Achieving 0 or 1 in PN-IGA Over Time Week 8	23.4 percentage of participants Interval 12.3 to 38.0	10.6 percentage of participants Interval 3.5 to 23.1	2.1 percentage of participants Interval 0.1 to 11.3	4.2 percentage of participants Interval 0.5 to 14.3	—	—
Phase 2b: Percentage of Participants Achieving 0 or 1 in PN-IGA Over Time Week 12	29.8 percentage of participants Interval 17.3 to 44.9	25.5 percentage of participants Interval 13.9 to 40.3	8.5 percentage of participants Interval 2.4 to 20.4	10.4 percentage of participants Interval 3.5 to 22.7	—	—
Phase 2b: Percentage of Participants Achieving 0 or 1 in PN-IGA Over Time Week 16	38.3 percentage of participants Interval 24.5 to 53.6	29.8 percentage of participants Interval 17.3 to 44.9	14.9 percentage of participants Interval 6.2 to 28.3	10.4 percentage of participants Interval 3.5 to 22.7	—	—
Phase 2b: Percentage of Participants Achieving 0 or 1 in PN-IGA Over Time Week 18	44.4 percentage of participants Interval 29.6 to 60.0	34.9 percentage of participants Interval 21.0 to 50.9	19.1 percentage of participants Interval 9.1 to 33.3	10.9 percentage of participants Interval 3.6 to 23.6	—	—
Phase 2b: Percentage of Participants Achieving 0 or 1 in PN-IGA Over Time Week 20	53.3 percentage of participants Interval 37.9 to 68.3	46.5 percentage of participants Interval 31.2 to 62.3	25.5 percentage of participants Interval 13.9 to 40.3	21.7 percentage of participants Interval 10.9 to 36.4	—	—
Phase 2b: Percentage of Participants Achieving 0 or 1 in PN-IGA Over Time Week 32	48.9 percentage of participants Interval 33.7 to 64.2	46.5 percentage of participants Interval 31.2 to 62.3	34.0 percentage of participants Interval 20.9 to 49.3	41.3 percentage of participants Interval 27.0 to 56.8	—	—
Phase 2b: Percentage of Participants Achieving 0 or 1 in PN-IGA Over Time Week 48	51.1 percentage of participants Interval 35.8 to 66.3	53.5 percentage of participants Interval 37.7 to 68.8	36.2 percentage of participants Interval 22.7 to 51.5	52.2 percentage of participants Interval 36.9 to 67.1	—	—
Phase 2b: Percentage of Participants Achieving 0 or 1 in PN-IGA Over Time Week 52	51.1 percentage of participants Interval 35.8 to 66.3	51.2 percentage of participants Interval 35.5 to 66.7	44.7 percentage of participants Interval 30.2 to 59.9	56.5 percentage of participants Interval 41.1 to 71.1	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Non-responders imputation.

PN-IGA is a novel exploratory tool for the overall investigator assessment of PN disease severity based on the size of the nodules as defined by their elevation. The IGA utilizes a 5-point scale that ranges from 0 (clear) to 4 (severe disease).

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Percentage of Participants With at Least 2-Point Improvement From Baseline in PN-IGA Over Time Week 2	6.4 percentage of participants Interval 1.3 to 17.5	2 percentage of participants Interval 0.5 to 14.5	6.4 percentage of participants Interval 1.3 to 17.5	2.1 percentage of participants Interval 0.1 to 11.1	—	—
Phase 2b: Percentage of Participants With at Least 2-Point Improvement From Baseline in PN-IGA Over Time Week 4	14.9 percentage of participants Interval 6.2 to 28.3	10.6 percentage of participants Interval 3.5 to 23.1	8.5 percentage of participants Interval 2.4 to 20.4	2.1 percentage of participants Interval 0.1 to 11.1	—	—
Phase 2b: Percentage of Participants With at Least 2-Point Improvement From Baseline in PN-IGA Over Time Week 8	27.7 percentage of participants Interval 15.6 to 42.6	21.3 percentage of participants Interval 10.7 to 35.7	8.5 percentage of participants Interval 2.4 to 20.4	4.2 percentage of participants Interval 0.5 to 14.3	—	—
Phase 2b: Percentage of Participants With at Least 2-Point Improvement From Baseline in PN-IGA Over Time Week 12	31.9 percentage of participants Interval 19.1 to 47.1	31.9 percentage of participants Interval 19.1 to 47.1	12.8 percentage of participants Interval 4.8 to 25.7	12.5 percentage of participants Interval 4.7 to 25.2	—	—
Phase 2b: Percentage of Participants With at Least 2-Point Improvement From Baseline in PN-IGA Over Time Week 16	38.3 percentage of participants Interval 24.5 to 53.6	40.4 percentage of participants Interval 26.4 to 55.7	25.5 percentage of participants Interval 13.9 to 40.3	12.5 percentage of participants Interval 4.7 to 25.2	—	—
Phase 2b: Percentage of Participants With at Least 2-Point Improvement From Baseline in PN-IGA Over Time Week 18	46.7 percentage of participants Interval 31.7 to 62.1	48.8 percentage of participants Interval 33.3 to 64.5	27.7 percentage of participants Interval 15.6 to 42.6	17.4 percentage of participants Interval 7.8 to 31.4	—	—
Phase 2b: Percentage of Participants With at Least 2-Point Improvement From Baseline in PN-IGA Over Time Week 20	57.8 percentage of participants Interval 42.2 to 72.3	58.1 percentage of participants Interval 42.1 to 73.0	34.0 percentage of participants Interval 20.9 to 49.3	26.1 percentage of participants Interval 14.3 to 41.1	—	—
Phase 2b: Percentage of Participants With at Least 2-Point Improvement From Baseline in PN-IGA Over Time Week 32	55.6 percentage of participants Interval 40.0 to 70.4	58.1 percentage of participants Interval 42.1 to 73.0	46.8 percentage of participants Interval 32.1 to 61.9	54.3 percentage of participants Interval 39.0 to 69.1	—	—
Phase 2b: Percentage of Participants With at Least 2-Point Improvement From Baseline in PN-IGA Over Time Week 48	57.8 percentage of participants Interval 42.2 to 72.3	62.8 percentage of participants Interval 46.7 to 77.0	40.4 percentage of participants Interval 26.4 to 55.7	58.7 percentage of participants Interval 43.2 to 73.0	—	—
Phase 2b: Percentage of Participants With at Least 2-Point Improvement From Baseline in PN-IGA Over Time Week 52	53.3 percentage of participants Interval 37.9 to 68.3	58.1 percentage of participants Interval 42.1 to 73.0	48.9 percentage of participants Interval 34.1 to 63.9	58.7 percentage of participants Interval 43.2 to 73.0	—	—

SECONDARY outcome

Timeframe: Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Non-responders imputation.

IGA-CNPG-S is a novel tool for the investigator assessment of PN disease severity based on the number of palpable nodules and utilizes a 5-point scale that ranges from 0 (clear) to 4 (severe); 0 (clear) indicates no nodules and 1 (almost clear) indicates rare palpable pruriginous nodules (approximately 1-5 nodules). A score is assigned based on the appearance of the disease at the time of the evaluation without referring to the baseline state.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Percentage of Participants Achieving 0 (Clear) or 1 (Almost Clear) in Investigator's Global Assessment for Prurigo Nodularis-Stage (IGA-CNPG-S) Over Time Week 2	4.3 percentage of participants Interval 0.5 to 14.5	2.1 percentage of participants Interval 0.1 to 11.3	2.1 percentage of participants Interval 0.1 to 11.3	0 percentage of participants Interval 0.0 to 7.4	—	—
Phase 2b: Percentage of Participants Achieving 0 (Clear) or 1 (Almost Clear) in Investigator's Global Assessment for Prurigo Nodularis-Stage (IGA-CNPG-S) Over Time Week 4	8.5 percentage of participants Interval 2.4 to 20.4	4.3 percentage of participants Interval 0.5 to 14.5	4.3 percentage of participants Interval 0.5 to 14.5	2.1 percentage of participants Interval 0.1 to 11.1	—	—
Phase 2b: Percentage of Participants Achieving 0 (Clear) or 1 (Almost Clear) in Investigator's Global Assessment for Prurigo Nodularis-Stage (IGA-CNPG-S) Over Time Week 8	14.9 percentage of participants Interval 6.2 to 28.3	10.6 percentage of participants Interval 3.5 to 23.1	2.1 percentage of participants Interval 0.1 to 11.3	4.2 percentage of participants Interval 0.5 to 14.3	—	—
Phase 2b: Percentage of Participants Achieving 0 (Clear) or 1 (Almost Clear) in Investigator's Global Assessment for Prurigo Nodularis-Stage (IGA-CNPG-S) Over Time Week 12	25.5 percentage of participants Interval 13.9 to 40.3	17.0 percentage of participants Interval 7.6 to 30.8	10.6 percentage of participants Interval 3.5 to 23.1	10.4 percentage of participants Interval 3.5 to 22.7	—	—
Phase 2b: Percentage of Participants Achieving 0 (Clear) or 1 (Almost Clear) in Investigator's Global Assessment for Prurigo Nodularis-Stage (IGA-CNPG-S) Over Time Week 16	34.0 percentage of participants Interval 20.9 to 49.3	25.5 percentage of participants Interval 13.9 to 40.3	14.9 percentage of participants Interval 6.2 to 28.3	6.3 percentage of participants Interval 1.3 to 17.2	—	—
Phase 2b: Percentage of Participants Achieving 0 (Clear) or 1 (Almost Clear) in Investigator's Global Assessment for Prurigo Nodularis-Stage (IGA-CNPG-S) Over Time Week 18	42.2 percentage of participants Interval 27.7 to 57.8	34.9 percentage of participants Interval 21.0 to 50.9	21.3 percentage of participants Interval 10.7 to 35.7	10.9 percentage of participants Interval 3.6 to 23.6	—	—
Phase 2b: Percentage of Participants Achieving 0 (Clear) or 1 (Almost Clear) in Investigator's Global Assessment for Prurigo Nodularis-Stage (IGA-CNPG-S) Over Time Week 32	44.4 percentage of participants Interval 29.6 to 60.0	41.9 percentage of participants Interval 27.0 to 57.9	21.3 percentage of participants Interval 10.7 to 35.7	34.8 percentage of participants Interval 21.4 to 50.2	—	—
Phase 2b: Percentage of Participants Achieving 0 (Clear) or 1 (Almost Clear) in Investigator's Global Assessment for Prurigo Nodularis-Stage (IGA-CNPG-S) Over Time Week 48	48.9 percentage of participants Interval 33.7 to 64.2	51.2 percentage of participants Interval 35.5 to 66.7	29.8 percentage of participants Interval 17.3 to 44.9	50.0 percentage of participants Interval 34.9 to 65.1	—	—
Phase 2b: Percentage of Participants Achieving 0 (Clear) or 1 (Almost Clear) in Investigator's Global Assessment for Prurigo Nodularis-Stage (IGA-CNPG-S) Over Time Week 20	42.2 percentage of participants Interval 27.7 to 57.8	39.5 percentage of participants Interval 25.0 to 55.6	21.3 percentage of participants Interval 10.7 to 35.7	17.4 percentage of participants Interval 7.8 to 31.4	—	—
Phase 2b: Percentage of Participants Achieving 0 (Clear) or 1 (Almost Clear) in Investigator's Global Assessment for Prurigo Nodularis-Stage (IGA-CNPG-S) Over Time Week 52	46.7 percentage of participants Interval 31.7 to 62.1	48.8 percentage of participants Interval 33.3 to 64.5	42.6 percentage of participants Interval 28.3 to 57.8	50.0 percentage of participants Interval 34.9 to 65.1	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period. Non-responders imputation.

IGA-CNPG-S, administered at designated visits, is a novel tool for the investigator assessment of PN disease severity based on the number of palpable nodules and utilizes a 5-point scale that ranges from 0 (clear) to 4 (severe). A score is assigned based on the appearance of the disease at the time of the evaluation without referring to the baseline state.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Percentage of Participants With at Least 2-point Improvement From Baseline in IGA-CNPG-S Over Time Week 2	4.3 percentage of participants Interval 0.5 to 14.5	6.4 percentage of participants Interval 1.3 to 17.5	4.3 percentage of participants Interval 0.5 to 14.5	2.1 percentage of participants Interval 0.1 to 11.1	—	—
Phase 2b: Percentage of Participants With at Least 2-point Improvement From Baseline in IGA-CNPG-S Over Time Week 4	12.8 percentage of participants Interval 4.8 to 25.7	10.6 percentage of participants Interval 3.5 to 23.1	8.5 percentage of participants Interval 2.4 to 20.4	2.1 percentage of participants Interval 0.1 to 11.1	—	—
Phase 2b: Percentage of Participants With at Least 2-point Improvement From Baseline in IGA-CNPG-S Over Time Week 8	19.1 percentage of participants Interval 9.1 to 33.3	12.8 percentage of participants Interval 4.8 to 25.7	8.5 percentage of participants Interval 2.4 to 20.4	4.2 percentage of participants Interval 0.5 to 14.3	—	—
Phase 2b: Percentage of Participants With at Least 2-point Improvement From Baseline in IGA-CNPG-S Over Time Week 12	27.7 percentage of participants Interval 15.6 to 42.6	25.5 percentage of participants Interval 13.9 to 40.3	14.9 percentage of participants Interval 6.2 to 28.3	12.5 percentage of participants Interval 4.7 to 25.2	—	—
Phase 2b: Percentage of Participants With at Least 2-point Improvement From Baseline in IGA-CNPG-S Over Time Week 16	34.0 percentage of participants Interval 20.9 to 49.3	34.0 percentage of participants Interval 20.9 to 49.3	25.5 percentage of participants Interval 13.9 to 40.3	12.5 percentage of participants Interval 4.7 to 25.2	—	—
Phase 2b: Percentage of Participants With at Least 2-point Improvement From Baseline in IGA-CNPG-S Over Time Week 18	46.7 percentage of participants Interval 31.7 to 62.1	41.9 percentage of participants Interval 27.0 to 57.9	29.8 percentage of participants Interval 17.3 to 44.9	19.6 percentage of participants Interval 9.4 to 33.9	—	—
Phase 2b: Percentage of Participants With at Least 2-point Improvement From Baseline in IGA-CNPG-S Over Time Week 20	44.4 percentage of participants Interval 29.6 to 60.0	46.5 percentage of participants Interval 31.2 to 62.3	31.9 percentage of participants Interval 19.1 to 47.1	30.4 percentage of participants Interval 17.7 to 45.8	—	—
Phase 2b: Percentage of Participants With at Least 2-point Improvement From Baseline in IGA-CNPG-S Over Time Week 32	48.9 percentage of participants Interval 33.7 to 64.2	51.2 percentage of participants Interval 35.5 to 66.7	36.2 percentage of participants Interval 22.7 to 51.5	52.2 percentage of participants Interval 36.9 to 67.1	—	—
Phase 2b: Percentage of Participants With at Least 2-point Improvement From Baseline in IGA-CNPG-S Over Time Week 52	53.3 percentage of participants Interval 37.9 to 68.3	55.8 percentage of participants Interval 39.9 to 70.9	46.8 percentage of participants Interval 32.1 to 61.9	60.9 percentage of participants Interval 45.4 to 74.9	—	—
Phase 2b: Percentage of Participants With at Least 2-point Improvement From Baseline in IGA-CNPG-S Over Time Week 48	53.3 percentage of participants Interval 37.9 to 72.3	60.5 percentage of participants Interval 44.4 to 75.0	38.3 percentage of participants Interval 24.5 to 53.6	56.5 percentage of participants Interval 41.1 to 71.1	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period; WOCF: Baseline through Week 52.

Participants rated intensity of their average sleeplessness over previous 3 days on 0-10 line scale (0=no sleeplessness, 10=worst imaginable sleeplessness). A score was set to missing after a participant received prohibited/rescue medication that potentially impact efficacy analyses prior to Week 16, and the participant's worst post baseline observation before the time of the medication usage was carried forward (WOCF) to impute missing endpoint value (for participants whose postbaseline values were all missing, the baseline was used to impute). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 2	-2.9 units on a scale Standard Deviation 0.40	-2.4 units on a scale Standard Deviation 0.39	-1.5 units on a scale Standard Deviation 0.41	-0.1 units on a scale Standard Deviation 0.38	—	—
Phase 2b: Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 4	-3.1 units on a scale Standard Deviation 0.34	-2.1 units on a scale Standard Deviation 0.35	-1.3 units on a scale Standard Deviation 0.36	-0.1 units on a scale Standard Deviation 0.33	—	—
Phase 2b: Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 8	-3.2 units on a scale Standard Deviation 0.42	-3.0 units on a scale Standard Deviation 0.41	-1.9 units on a scale Standard Deviation 0.41	-1.0 units on a scale Standard Deviation 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 12	-3.6 units on a scale Standard Deviation 0.43	-3.2 units on a scale Standard Deviation 0.43	-1.8 units on a scale Standard Deviation 0.45	-1.1 units on a scale Standard Deviation 0.45	—	—
Phase 2b: Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 18	-3.8 units on a scale Standard Deviation 0.43	-3.6 units on a scale Standard Deviation 0.44	-2.4 units on a scale Standard Deviation 0.45	-2.3 units on a scale Standard Deviation 0.47	—	—
Phase 2b: Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 20	-3.9 units on a scale Standard Deviation 0.38	-3.8 units on a scale Standard Deviation 0.39	-2.7 units on a scale Standard Deviation 0.39	-3.0 units on a scale Standard Deviation 0.39	—	—
Phase 2b: Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 32	-4.1 units on a scale Standard Deviation 0.38	-4.1 units on a scale Standard Deviation 0.40	-3.3 units on a scale Standard Deviation 0.40	-3.5 units on a scale Standard Deviation 0.39	—	—
Phase 2b: Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 52	-4.5 units on a scale Standard Deviation 0.41	-4.4 units on a scale Standard Deviation 0.42	-3.8 units on a scale Standard Deviation 0.42	-3.9 units on a scale Standard Deviation 0.41	—	—
Phase 2b: Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 16	-3.5 units on a scale Standard Deviation 0.43	-3.3 units on a scale Standard Deviation 0.44	-2.1 units on a scale Standard Deviation 0.44	-1.5 units on a scale Standard Deviation 0.44	—	—
Phase 2b: Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 48	-4.5 units on a scale Standard Deviation 0.40	-4.4 units on a scale Standard Deviation 0.40	-3.7 units on a scale Standard Deviation 0.38	-3.7 units on a scale Standard Deviation 0.39	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period; WOCF: Baseline through Week 52.

Participants rated intensity of their average sleeplessness over previous 3 days on 0-10 line scale (0=no sleeplessness, 10=worst imaginable sleeplessness). A score was set to missing after a participant received prohibited/rescue medication that potentially impact efficacy analyses prior to Week 16, and the participant's worst post baseline observation before the time of the medication usage was carried forward (WOCF) to impute missing endpoint value (for participants whose postbaseline values were all missing, the baseline was used to impute). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Percent Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 2	-63.6 percentage change Standard Error 26.46	-24.9 percentage change Standard Error 25.73	-28.5 percentage change Standard Error 27.03	81.4 percentage change Standard Error 25.30	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 4	-50.6 percentage change Standard Error 10.74	-30.2 percentage change Standard Error 11.03	-18.1 percentage change Standard Error 11.34	25.2 percentage change Standard Error 10.53	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 8	-36.7 percentage change Standard Error 15.47	-48.2 percentage change Standard Error 15.12	-25.3 percentage change Standard Error 15.39	5.9 percentage change Standard Error 15.22	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 12	-62.4 percentage change Standard Error 19.30	-46.1 percentage change Standard Error 19.73	-26.7 percentage change Standard Error 20.58	25.6 percentage change Standard Error 20.17	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 18	-55.1 percentage change Standard Error 11.14	-44.7 percentage change Standard Error 11.35	-29.0 percentage change Standard Error 11.90	-22.4 percentage change Standard Error 12.24	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 20	-64.9 percentage change Standard Error 9.83	-56.8 percentage change Standard Error 10.36	-37.0 percentage change Standard Error 10.39	-27.6 percentage change Standard Error 10.30	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 32	-66.4 percentage change Standard Error 10.57	-56.5 percentage change Standard Error 11.17	-41.8 percentage change Standard Error 11.14	-38.3 percentage change Standard Error 10.60	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 48	-71.2 percentage change Standard Error 10.88	-67.3 percentage change Standard Error 11.19	-49.9 percentage change Standard Error 10.66	-44.0 percentage change Standard Error 10.75	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 52	-67.8 percentage change Standard Error 10.85	-65.4 percentage change Standard Error 11.43	-55.0 percentage change Standard Error 11.41	-49.3 percentage change Standard Error 11.03	—	—
Phase 2b: Percent Change From Baseline in Weekly Average of Sleep Loss VAS Over Time Week 16	-57.4 percentage change Standard Error 9.75	-46.3 percentage change Standard Error 10.02	-28.6 percentage change Standard Error 10.11	-12.3 percentage change Standard Error 9.98	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 18, 20, 32, 48, 52

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period; WOCF: Baseline through Week 52.

ItchyQoL focuses on impact of pruritus on daily activities and on the level of psychological stress. It contains 22 items. The frequency items are scored using a 5-point Likert scale ranging from "never" to "all the time". The bother items are scored from 1 (not bothered) to 5 (severely bothered). The recall period in ItchyQoL is the past week. The ItchyQoL total score is defined as the sum of all 22-items scores. Total scores can be classified as little (0-30), mild (31-50), moderate (51-80), and severe (81-110). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Change From Baseline in ItchyQoL Over Time Week 12	-27.0 score on a scale Standard Error 2.93	-22.7 score on a scale Standard Error 2.96	-15.4 score on a scale Standard Error 3.09	-6.4 score on a scale Standard Error 3.07	—	—
Phase 2b: Change From Baseline in ItchyQoL Over Time Week 8	-26.1 score on a scale Standard Error 2.57	-17.4 score on a scale Standard Error 2.52	-12.1 score on a scale Standard Error 2.54	-5.1 score on a scale Standard Error 2.54	—	—
Phase 2b: Change From Baseline in ItchyQoL Over Time Week 16	-28.8 score on a scale Standard Error 2.78	-23.4 score on a scale Standard Error 2.83	-18.2 score on a scale Standard Error 2.87	-7.8 score on a scale Standard Error 2.87	—	—
Phase 2b: Change From Baseline in ItchyQoL Over Time Week 18	-30.6 score on a scale Standard Error 2.93	-27.7 score on a scale Standard Error 2.98	-22.5 score on a scale Standard Error 3.07	-17.9 score on a scale Standard Error 3.22	—	—
Phase 2b: Change From Baseline in ItchyQoL Over Time Week 20	-31.0 score on a scale Standard Error 2.85	-28.3 score on a scale Standard Error 2.96	-25.1 score on a scale Standard Error 2.99	-23.7 score on a scale Standard Error 3.00	—	—
Phase 2b: Change From Baseline in ItchyQoL Over Time Week 48	-34.8 score on a scale Standard Error 3.24	-30.6 score on a scale Standard Error 3.27	-27.9 score on a scale Standard Error 3.15	-30.4 score on a scale Standard Error 3.20	—	—
Phase 2b: Change From Baseline in ItchyQoL Over Time Week 52	-34.7 score on a scale Standard Error 3.22	-34.0 score on a scale Standard Error 3.32	-31.1 score on a scale Standard Error 3.30	-29.8 score on a scale Standard Error 3.27	—	—
Phase 2b: Change From Baseline in ItchyQoL Over Time Week 4	-19.7 score on a scale Standard Error 2.19	-13.4 score on a scale Standard Error 2.23	-11.5 score on a scale Standard Error 2.26	-1.7 score on a scale Standard Error 2.15	—	—
Phase 2b: Change From Baseline in ItchyQoL Over Time Week 32	-33.9 score on a scale Standard Error 3.09	-29.4 score on a scale Standard Error 3.21	-27.8 score on a scale Standard Error 3.22	-26.0 score on a scale Standard Error 3.11	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 18, 20, 32, 48, 52

Population: mITT Analysis Set: All randomized participants who receive at least 1 dose of vixarelimab or placebo and have at least 1 post-baseline efficacy assessment in the double-blind treatment period; WOCF: Baseline through Week 52.

ItchyQoL focuses on impact of pruritus on daily activities and on the level of psychological stress. It contains 22 items. The frequency items are scored using a 5-point Likert scale ranging from "never" to "all the time". The bother items are scored from 1 (not bothered) to 5 (severely bothered). The recall period in ItchyQoL is the past week. The ItchyQoL total score is defined as the sum of all 22-items scores. Total scores can be classified as little (0-30), mild (31-50), moderate (51-80), and severe (81-110). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.

Outcome measures

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=47 Participants Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=47 Participants Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 Participants Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) n=48 Participants Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) Vixarelimab 120 mg SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).	Phase 2b - Placebo SC, Q4W (DBL), Then Vixarelimab (OLE) Placebo SC, Q4W for 16 weeks during double blind (DBL) period. Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during open label extension (OLE).
Phase 2b: Percent Change From Baseline in ItchyQoL Over Time Week 4	-25.4 percentage change Standard Error 2.88	-17.2 percentage change Standard Error 2.93	-13.8 percentage change Standard Error 2.97	-0.6 percentage change Standard Error 2.83	—	—
Phase 2b: Percent Change From Baseline in ItchyQoL Over Time Week 8	-32.8 percentage change Standard Error 3.18	-21.8 percentage change Standard Error 3.11	-13.6 percentage change Standard Error 3.14	-5.0 percentage change Standard Error 3.14	—	—
Phase 2b: Percent Change From Baseline in ItchyQoL Over Time Week 12	-34.0 percentage change Standard Error 3.66	-28.4 percentage change Standard Error 3.70	-17.7 percentage change Standard Error 3.87	-6.5 percentage change Standard Error 3.84	—	—
Phase 2b: Percent Change From Baseline in ItchyQoL Over Time Week 16	-36.4 percentage change Standard Error 3.45	-29.5 percentage change Standard Error 3.51	-21.1 percentage change Standard Error 3.56	-8.3 percentage change Standard Error 3.55	—	—
Phase 2b: Percent Change From Baseline in ItchyQoL Over Time Week 18	-39.3 percentage change Standard Error 3.69	-34.8 percentage change Standard Error 3.76	-26.7 percentage change Standard Error 3.87	-20.3 percentage change Standard Error 4.06	—	—
Phase 2b: Percent Change From Baseline in ItchyQoL Over Time Week 20	-39.9 percentage change Standard Error 3.60	-35.8 percentage change Standard Error 3.74	-30.3 percentage change Standard Error 3.77	-28.2 percentage change Standard Error 3.79	—	—
Phase 2b: Percent Change From Baseline in ItchyQoL Over Time Week 32	-43.5 percentage change Standard Error 4.04	-36.4 percentage change Standard Error 4.20	-33.5 percentage change Standard Error 4.21	-31.3 percentage change Standard Error 4.07	—	—
Phase 2b: Percent Change From Baseline in ItchyQoL Over Time Week 48	-44.4 percentage change Standard Error 4.16	-38.3 percentage change Standard Error 4.20	-34.4 percentage change Standard Error 4.04	-36.2 percentage change Standard Error 4.11	—	—
Phase 2b: Percent Change From Baseline in ItchyQoL Over Time Week 52	-44.5 percentage change Standard Error 4.19	-43.0 percentage change Standard Error 4.31	-37.7 percentage change Standard Error 4.30	-36.3 percentage change Standard Error 4.26	—	—

Adverse Events

Phase 2a - Vixarelimab 360 mg SC QW

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Phase 2a - Placebo SC QW

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Phase 2b - Vixarelimab 540 mg SC Q4W (DBL)

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Phase 2b - Vixarelimab 360 mg SC, Q4W (DBL)

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL)

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Phase 2b - Placebo SC, Q4W (DBL)

Serious events: 3 serious events

Other events: 14 other events

Deaths: 0 deaths

Phase 2b - Vixarelimab 360 mg SC, Q2W (OLE Period)

Serious events: 8 serious events

Other events: 77 other events

Deaths: 0 deaths

Serious adverse events

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 participants at risk Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 participants at risk Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 540 mg SC Q4W (DBL) n=47 participants at risk Vixarelimab 540 mg SC, every 4 weeks (Q4W) for 16 weeks during the double-blind (DBL) period.	Phase 2b - Vixarelimab 360 mg SC, Q4W (DBL) n=47 participants at risk Vixarelimab 360 mg SC, Q4W for 16 weeks during the double-blind (DBL) period.	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 participants at risk Vixarelimab 120 mg SC, Q4W for 16 weeks during the double-blind (DBL) period.	Phase 2b - Placebo SC, Q4W (DBL) n=48 participants at risk Placebo SC, Q4W for 16 weeks during the double-blind (DBL) period.	Phase 2b - Vixarelimab 360 mg SC, Q2W (OLE Period) n=181 participants at risk Vixarelimab 360 mg SC, every 2 weeks (Q2W) for 36 weeks during the open-label extension (OLE) period.
Cardiac disorders Supraventricular extrasystoles	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.55% 1/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Gastrointestinal disorders Ileus	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.55% 1/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Gastrointestinal disorders Rectal ulcer	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.55% 1/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Hepatobiliary disorders Cholelithiasis	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Infections and infestations Periorbital cellulitis	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.55% 1/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Injury, poisoning and procedural complications Spinal fusion fracture	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.55% 1/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Nervous system disorders Facial paralysis	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.55% 1/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Nervous system disorders Syncope	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Nervous system disorders Transient ischaemic attack	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Skin and subcutaneous tissue disorders Eczema nummular	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	1.1% 2/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.

Other adverse events

Measure	Phase 2a - Vixarelimab 360 mg SC QW n=23 participants at risk Vixarelimab 720 mg loading dose followed by 360 mg subcutaneously (SC) weekly (QW) for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2a - Placebo SC QW n=26 participants at risk Placebo loading dose followed by placebo SC QW for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2).	Phase 2b - Vixarelimab 540 mg SC Q4W (DBL) n=47 participants at risk Vixarelimab 540 mg SC, every 4 weeks (Q4W) for 16 weeks during the double-blind (DBL) period.	Phase 2b - Vixarelimab 360 mg SC, Q4W (DBL) n=47 participants at risk Vixarelimab 360 mg SC, Q4W for 16 weeks during the double-blind (DBL) period.	Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) n=47 participants at risk Vixarelimab 120 mg SC, Q4W for 16 weeks during the double-blind (DBL) period.	Phase 2b - Placebo SC, Q4W (DBL) n=48 participants at risk Placebo SC, Q4W for 16 weeks during the double-blind (DBL) period.	Phase 2b - Vixarelimab 360 mg SC, Q2W (OLE Period) n=181 participants at risk Vixarelimab 360 mg SC, every 2 weeks (Q2W) for 36 weeks during the open-label extension (OLE) period.
General disorders Fatigue	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	10.6% 5/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	1.7% 3/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Infections and infestations COVID-19	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	6.4% 3/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	8.3% 4/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	15.5% 28/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Infections and infestations Nasopharyngitis	13.0% 3/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	15.4% 4/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	8.5% 4/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	4.2% 2/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	7.7% 14/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Infections and infestations Upper respiratory tract infection	21.7% 5/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	7.7% 2/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	4.3% 2/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	4.2% 2/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	8.8% 16/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Infections and infestations Urinary tract infection	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	15.4% 4/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	3.3% 6/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Injury, poisoning and procedural complications Procedural headache	8.7% 2/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	3.8% 1/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Nervous system disorders Headache	13.0% 3/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	11.5% 3/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	8.5% 4/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	4.3% 2/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	6.4% 3/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	3.3% 6/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Psychiatric disorders Insomnia	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	6.2% 3/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.8% 5/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	5.5% 10/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	8.5% 4/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	4.3% 2/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	7.7% 14/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Skin and subcutaneous tissue disorders Eczema nummular	8.7% 2/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	3.8% 1/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	3.3% 6/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Skin and subcutaneous tissue disorders Skin burning sensation	0.00% 0/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	7.7% 2/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.55% 1/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Skin and subcutaneous tissue disorders Urticaria	8.7% 2/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	4.3% 2/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.1% 1/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.2% 4/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.
Vascular disorders Hypertension	4.3% 1/23 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	3.8% 1/26 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	4.3% 2/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	0.00% 0/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	4.3% 2/47 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	6.2% 3/48 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.	2.8% 5/181 • Phase 2a: From the Screening Visit through end of study (EOS) Visit (Week 24). Phase 2b: Double-blind (DBL) period: after signing the informed consent form (ICF) until Week 16; Open-label extension (OLE) period: End of Week 16 until Week 52.

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