Trial Outcomes & Findings for Study of VIB7734 for the Treatment of Moderate to Severely Active SLE (NCT NCT04925934)

Last Updated: 2024-07-23

Results Overview

A BICLA response required improvement in all domains affected at baseline, assessed by the BILAG 2004, no worsening of other BILAG 2004 domains, no worsening of SLEDAI-2K or PGA scores compared with baseline, no use of restricted medications beyond the protocol-allowed threshold, and no discontinuation of IP.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

214 participants

Primary outcome timeframe

Week 48

Results posted on

2024-07-23

Participant Flow

Participants with systemic lupus erythematosus (SLE) were enrolled at 68 sites in the United States, Argentina, Greece, India, Mexico, Poland, Serbia, Spain, Taiwan, Ukraine and Russia between May 2021 and June 2023.

Participants were randomized in a 1:1:1 ratio to take daxdilimab 200 mg every 4 weeks (Q4W) subcutaneously (SC), daxdilimab 200 mg every 12 weeks (Q12W) SC (with an additional 200 mg SC dose at Week 4) or matching placebo Q4W SC. Duration of treatment was up to 48 weeks. Randomization was stratified by SLE Disease Activity Index 2000 (SLEDAI-2K) total score at screening (≥ 10 or \< 10) and prednisone or equivalent oral glucocorticoid (OGC) dose at baseline (≥ 10 mg/day or \< 10 mg/day).

Participant milestones

Participant milestones
Measure	Placebo Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q4W Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q12W Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.
Overall Study STARTED	71	72	71
Overall Study COMPLETED	51	61	57
Overall Study NOT COMPLETED	20	11	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q4W Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q12W Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.
Overall Study Adverse Event	1	0	0
Overall Study Lost to Follow-up	2	0	1
Overall Study Death	0	1	0
Overall Study Withdrawal by Subject	8	5	9
Overall Study Other	2	2	2
Overall Study Eastern European Conflict	7	3	2

Baseline Characteristics

Study of VIB7734 for the Treatment of Moderate to Severely Active SLE

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=71 Participants Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q4W n=72 Participants Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q12W n=71 Participants Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.	Total n=214 Participants Total of all reporting groups
Age, Continuous	41.0 years STANDARD_DEVIATION 11.0 • n=5 Participants	44.5 years STANDARD_DEVIATION 13.1 • n=7 Participants	45.3 years STANDARD_DEVIATION 11.6 • n=5 Participants	43.6 years STANDARD_DEVIATION 12.0 • n=4 Participants
Sex: Female, Male Female	67 Participants n=5 Participants	67 Participants n=7 Participants	66 Participants n=5 Participants	200 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	14 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	2 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	4 participants n=4 Participants
Race/Ethnicity, Customized Asian	9 participants n=5 Participants	7 participants n=7 Participants	10 participants n=5 Participants	26 participants n=4 Participants
Race/Ethnicity, Customized Black or African American	4 participants n=5 Participants	8 participants n=7 Participants	6 participants n=5 Participants	18 participants n=4 Participants
Race/Ethnicity, Customized White	54 participants n=5 Participants	49 participants n=7 Participants	51 participants n=5 Participants	154 participants n=4 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	6 participants n=7 Participants	4 participants n=5 Participants	11 participants n=4 Participants
Race/Ethnicity, Customized Multiple categories checked	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	25 participants n=5 Participants	27 participants n=7 Participants	27 participants n=5 Participants	79 participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	46 participants n=5 Participants	45 participants n=7 Participants	44 participants n=5 Participants	135 participants n=4 Participants
Number of Participants Within Each OGC Stratification Dose Level < 10 mg/day	36 number of participants n=5 Participants	35 number of participants n=7 Participants	36 number of participants n=5 Participants	107 number of participants n=4 Participants
Number of Participants Within Each OGC Stratification Dose Level ≥ 10 mg/day	35 number of participants n=5 Participants	37 number of participants n=7 Participants	35 number of participants n=5 Participants	107 number of participants n=4 Participants
SLEDAI-2K Score	9.9 Score STANDARD_DEVIATION 2.8 • n=5 Participants	10.6 Score STANDARD_DEVIATION 4.0 • n=7 Participants	10.1 Score STANDARD_DEVIATION 2.9 • n=5 Participants	10.2 Score STANDARD_DEVIATION 3.3 • n=4 Participants
British Isles Lupus Assessment Group (BILAG)-2004 Score	19.2 scores on a scale STANDARD_DEVIATION 4.7 • n=5 Participants	19.5 scores on a scale STANDARD_DEVIATION 4.6 • n=7 Participants	19.8 scores on a scale STANDARD_DEVIATION 5.5 • n=5 Participants	19.5 scores on a scale STANDARD_DEVIATION 4.9 • n=4 Participants
Physician Global Assessment (PGA) Score	1.89 Score STANDARD_DEVIATION 0.37 • n=5 Participants	1.96 Score STANDARD_DEVIATION 0.32 • n=7 Participants	1.90 Score STANDARD_DEVIATION 0.41 • n=5 Participants	1.91 Score STANDARD_DEVIATION 0.37 • n=4 Participants

PRIMARY outcome

Timeframe: Week 48

Population: FAS: included all randomized participants who received any dose of IP. Participants were analyzed according to the treatment randomized.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q4W n=69 Participants Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q12W n=69 Participants Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.
Number of Participants Achieving a BILAG-2004 Index-based Combined Lupus Assessment (BICLA) Response and an OGC Dose ≤ 7.5 mg/Day and ≤ Baseline Dose of Prednisone or Equivalent at Week 48	25 Participants	29 Participants	27 Participants

SECONDARY outcome

Timeframe: Week 12

Population: FAS: included all randomized participants who received any dose of IP. Participants were analyzed according to the treatment randomized. Only participants with a CLASI-A score ≥ 10 at baseline were included in the analysis.

The CLASI-A evaluates erythema (0-3 \[higher scores indicate more severe redness\]), scale/hypertrophy (0-2 \[higher scores indicate more extensive scaling/thickening\]), mucous membrane lesions (0 \[absent\] or 1 \[present\]), recent hair loss (0 \[absent\] or 1 \[present\]), and non-scarring alopecia (0-3 \[(higher scores indicate more extensive hair loss without scarring\]) at 13 anatomical sites on the skin. Total score is calculated by summing scores across all anatomical locations for each parameter. Higher total scores indicate greater disease activity and severity in SLE. Reduction of 50% in CLASI-A score was defined by meeting all the following conditions: 1. A ≥ 50% reduction of CLASI-A score at Week 12 as compared to baseline. 2. No use of restricted medications beyond the protocol-allowed threshold before assessment. 3. No discontinuation of IP.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q4W n=10 Participants Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q12W n=14 Participants Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.
Number of Participants With a Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) Score ≥ 10 at Baseline Achieving ≥ 50% Reduction From Baseline in CLASI-A Score at Week 12	1 Participants	4 Participants	5 Participants

SECONDARY outcome

Timeframe: Week 48

Population: FAS: included all randomized participants who received any dose of IP. Participants were analyzed according to the treatment randomized.

The SRI-4 measures reduction in SLE disease activity and it is a composite measure that includes the SLEDAI-2K, BILAG-2004, and PGA. SRI responder was defined by meeting all of the following criteria: 1) Reduction of ≥4 points from baseline in SLEDAI-2K score; 2) no new BILAG A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[0-3 scale\] from baseline) in the PGA.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q4W n=69 Participants Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q12W n=69 Participants Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.
Number of Participants Achieving an SLE Responder Index (SRI)-4 Response and an OGC Dose ≤ 7.5 mg/Day and ≤ Baseline Dose of Prednisone or Equivalent at Week 48	26 Participants	34 Participants	30 Participants

SECONDARY outcome

Timeframe: Week 36 up to Week 48

Population: FAS: included all randomized participants who received any dose of IP. Participants were analyzed according to the treatment randomized. Data excludes participants from Russia and Ukraine sites. Only participants with an OGC dose ≥ 10 mg/day of prednisone or equivalent at baseline were included in the analysis.

Maintenance of OGC reduction from Week 36 to Week 48 was defined by meeting all the following criteria: 1. Achieved an OGC dose of ≤ 7.5 mg/day prednisone or equivalent at Week 36 2. Maintained an OGC dose of ≤ 7.5 mg/day from Week 36 through Week 48 3. No use of restricted medications beyond the protocol-allowed threshold before assessment 4. No discontinuation of IP before assessment

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q4W n=34 Participants Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q12W n=34 Participants Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.
Number of Participants With an OGC Dose ≥ 10 mg/Day of Prednisone or Equivalent at Baseline Who Maintained an OGC Dose ≤ 7.5 mg/Day From Week 36 Through Week 48	20 Participants	27 Participants	26 Participants

SECONDARY outcome

Timeframe: Week 48

Population: FAS: included all randomized participants who received any dose of IP. Participants were analyzed according to the treatment randomized.

LLDAS was defined by meeting all of the following criteria: 1. SLEDAI-2K ≤ 4, with no activity in major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity measured as maintaining a D (no disease activity but suggests the system had previously been affected) or E (no current or previous disease activity) score in BILAG Gastrointestinal Body System 2. No new lupus disease activity compared with the previous 3. Physician's Global Assessment of Disease Activity ≤ 1 on a 3-point visual analog scale from no disease activity to severe disease activity 4. A current prednisolone (or equivalent) dose ≤ 7.5 mg daily 5. Well-tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q4W n=69 Participants Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q12W n=69 Participants Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.
Number of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 48	11 Participants	23 Participants	15 Participants

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48

Population: Pharmacokinetic (PK) analysis set: included all participants who received any dose of daxdilimab in the study and had at least 1 quantifiable serum PK observation post-first dose. Participants were analyzed according to the treatment that they received.

Outcome measures

Outcome measures
Measure	Placebo Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q4W n=72 Participants Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q12W n=71 Participants Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.
Serum Concentration of Daxdilimab Week 44	—	4.908 ug/mL Standard Deviation 3.780	1.115 ug/mL Standard Deviation 1.378
Serum Concentration of Daxdilimab Baseline	—	0.011 ug/mL Standard Deviation 0.026	0.008 ug/mL Standard Deviation 0.004
Serum Concentration of Daxdilimab Week 4	—	3.319 ug/mL Standard Deviation 1.972	3.301 ug/mL Standard Deviation 1.718
Serum Concentration of Daxdilimab Week 8	—	4.714 ug/mL Standard Deviation 3.079	4.643 ug/mL Standard Deviation 2.708
Serum Concentration of Daxdilimab Week 12	—	5.344 ug/mL Standard Deviation 3.624	1.372 ug/mL Standard Deviation 1.189
Serum Concentration of Daxdilimab Week 16	—	5.035 ug/mL Standard Deviation 3.377	4.268 ug/mL Standard Deviation 2.720
Serum Concentration of Daxdilimab Week 20	—	5.884 ug/mL Standard Deviation 4.451	1.239 ug/mL Standard Deviation 1.097
Serum Concentration of Daxdilimab Week 24	—	5.539 ug/mL Standard Deviation 4.224	0.530 ug/mL Standard Deviation 0.922
Serum Concentration of Daxdilimab Week 28	—	4.855 ug/mL Standard Deviation 3.743	3.590 ug/mL Standard Deviation 2.522
Serum Concentration of Daxdilimab Week 32	—	4.951 ug/mL Standard Deviation 4.047	1.096 ug/mL Standard Deviation 1.151
Serum Concentration of Daxdilimab Week 36	—	5.321 ug/mL Standard Deviation 4.309	0.366 ug/mL Standard Deviation 0.471
Serum Concentration of Daxdilimab Week 40	—	4.652 ug/mL Standard Deviation 3.426	3.439 ug/mL Standard Deviation 2.534
Serum Concentration of Daxdilimab Week 48	—	5.543 ug/mL Standard Deviation 4.637	0.406 ug/mL Standard Deviation 0.585

SECONDARY outcome

Timeframe: Baseline to Week 56

Population: Safety analysis set (SAS): included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received.

A baseline ADA-positive participant was defined as a participant who had an ADA positive sample at baseline. ADA incidence is the number of the participants ADA positive post-Baseline only or who boosted their preexisting ADA (≥ 4 × Baseline level) during the trial. Persistent positive was defined as ADA positive at ≥ 2 post-Baseline assessments (with ≥ 16 weeks between first and last positive) or positive at last post-Baseline assessment. Transient positive was defined as ADA post-Baseline positive but did not fulfill the criteria of persistent positive.

Outcome measures

Outcome measures
Measure	Placebo n=71 Participants Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q4W n=72 Participants Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q12W n=71 Participants Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.
Number of Participants With Anti-drug Antibodies (ADA) to Daxdilimab Only post-Baseline positive	13 Participants	4 Participants	4 Participants
Number of Participants With Anti-drug Antibodies (ADA) to Daxdilimab Boosted ADA (≥ 4 × Baseline level)	1 Participants	2 Participants	2 Participants
Number of Participants With Anti-drug Antibodies (ADA) to Daxdilimab ADA detected (positive) on trial: ADA prevalence	24 Participants	13 Participants	15 Participants
Number of Participants With Anti-drug Antibodies (ADA) to Daxdilimab Only Baseline positive	1 Participants	5 Participants	5 Participants
Number of Participants With Anti-drug Antibodies (ADA) to Daxdilimab Both Baseline and post-Baseline positive	10 Participants	4 Participants	6 Participants
Number of Participants With Anti-drug Antibodies (ADA) to Daxdilimab Persistent positive	19 Participants	8 Participants	8 Participants
Number of Participants With Anti-drug Antibodies (ADA) to Daxdilimab Transient positive	4 Participants	0 Participants	2 Participants
Number of Participants With Anti-drug Antibodies (ADA) to Daxdilimab ADA not detected (negative) on trial	47 Participants	59 Participants	56 Participants
Number of Participants With Anti-drug Antibodies (ADA) to Daxdilimab ADA incidence	14 Participants	6 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12, Week 20, Week 24, Week 32, Week 36, Week 44, Week 48, Week 52, Week 56

Population: SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. Only participants with available data were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q4W n=48 Participants Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q12W n=46 Participants Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.
Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood Week 56	-2.0823 cells/uL Standard Deviation 3.9807	-2.3137 cells/uL Standard Deviation 3.2514	-0.7056 cells/uL Standard Deviation 0.6729
Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood Baseline	2.5068 cells/uL Standard Deviation 1.8486	2.2960 cells/uL Standard Deviation 1.7457	1.9195 cells/uL Standard Deviation 1.1990
Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood Week 4	-0.2324 cells/uL Standard Deviation 1.8194	-1.4240 cells/uL Standard Deviation 1.9493	-1.2903 cells/uL Standard Deviation 1.2201
Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood Week 8	-0.4608 cells/uL Standard Deviation 1.4125	-1.5194 cells/uL Standard Deviation 1.7555	-1.1486 cells/uL Standard Deviation 1.2090
Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood Week 12	0.0275 cells/uL Standard Deviation 1.7580	-1.5164 cells/uL Standard Deviation 1.8180	-1.1134 cells/uL Standard Deviation 1.5290
Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood Week 20	285.1519 cells/uL Standard Deviation 1613.566	-1.5131 cells/uL Standard Deviation 1.6837	-1.0320 cells/uL Standard Deviation 1.1063
Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood Week 24	-0.3911 cells/uL Standard Deviation 1.7344	-1.5974 cells/uL Standard Deviation 1.7705	-0.5507 cells/uL Standard Deviation 1.3090
Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood Week 32	0.3513 cells/uL Standard Deviation 1.7855	-1.3367 cells/uL Standard Deviation 1.5678	-0.8496 cells/uL Standard Deviation 1.2403
Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood Week 36	-0.1274 cells/uL Standard Deviation 1.6962	-1.4614 cells/uL Standard Deviation 1.7634	-0.9131 cells/uL Standard Deviation 0.9845
Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood Week 44	-0.3194 cells/uL Standard Deviation 1.6347	-1.6540 cells/uL Standard Deviation 1.6184	-1.1322 cells/uL Standard Deviation 1.3782
Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood Week 48	0.1973 cells/uL Standard Deviation 2.4112	-1.4608 cells/uL Standard Deviation 1.5647	-0.7964 cells/uL Standard Deviation 1.0055
Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood Week 52	0.1483 cells/uL Standard Deviation 3.7955	-0.4353 cells/uL Standard Deviation 0.5127	0.0149 cells/uL Standard Deviation 0.7999

SECONDARY outcome

Timeframe: Up to Week 56

Population: SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received.

An adverse event (AE) is any untoward medical occurrence associated with the use of an intervention in humans whether or not it is considered intervention-related. TEAEs are AEs that started on or after the first dose of IP. An AE was considered serious (SAE) if it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolonged existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital abnormality/birth defect, or an important medical event. AE severity was rated according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).

Outcome measures

Outcome measures
Measure	Placebo n=71 Participants Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q4W n=72 Participants Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q12W n=71 Participants Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) Treatment-related TEAEs	10 Participants	17 Participants	17 Participants
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) AEs Grade 3 or higher	5 Participants	8 Participants	9 Participants
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) SAEs	8 Participants	9 Participants	9 Participants
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) Treatment-related SAEs	0 Participants	1 Participants	0 Participants
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) TEAEs	49 Participants	49 Participants	58 Participants
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) AEs Resulting in Death	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 56

Population: SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received.

An AESI is an AE of scientific and medical interest specific to understanding of the IP and may require close monitoring and collection of additional information by the Investigator. AESIs for this study included: 1. Hypersensitivity reaction, including anaphylaxis. 2. Severe (Grade 3 or higher) viral infections/reactivations. 3. Opportunistic infection. 4. Malignancy (except non-melanoma skin cancer).

Outcome measures

Outcome measures
Measure	Placebo n=71 Participants Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q4W n=72 Participants Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.	Daxdilimab 200 mg Q12W n=71 Participants Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.
Number of Participants Who Experienced AEs of Special Interest (AESI) Hypersensitivity Reaction Including Anaphylaxis	1 Participants	0 Participants	1 Participants
Number of Participants Who Experienced AEs of Special Interest (AESI) Opportunistic infection	1 Participants	1 Participants	1 Participants
Number of Participants Who Experienced AEs of Special Interest (AESI) Viral infection/Reactivation	10 Participants	6 Participants	7 Participants

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 17 other events

Deaths: 0 deaths

Daxdilimab 200mg Q4W

Serious events: 9 serious events

Other events: 30 other events

Deaths: 1 deaths

Daxdilimab 200mg Q12W

Serious events: 9 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=71 participants at risk Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.	Daxdilimab 200mg Q4W n=72 participants at risk Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.	Daxdilimab 200mg Q12W n=71 participants at risk Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.
Cardiac disorders Palpitations	0.00% 0/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	5.6% 4/72 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	0.00% 0/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	1.4% 1/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	5.6% 4/72 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	2.8% 2/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	1.4% 1/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	0.00% 0/72 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	5.6% 4/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations COVID-19	12.7% 9/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	13.9% 10/72 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	12.7% 9/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Influenza	0.00% 0/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	5.6% 4/72 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	2.8% 2/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	5.6% 4/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	4.2% 3/72 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	2.8% 2/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Sinusitis	1.4% 1/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	5.6% 4/72 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	2.8% 2/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection bacterial	2.8% 2/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	1.4% 1/72 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	5.6% 4/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	5.6% 4/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	9.7% 7/72 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	11.3% 8/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Nervous system disorders Headache	7.0% 5/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	4.2% 3/72 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.	1.4% 1/71 • Up to 56 weeks SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER