Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of Ruxolitinib Cream in Participants With Prurigo Nodularis (PN) (NCT NCT05755438)

Last Updated: 2025-11-14

Results Overview

WI-NRS4 was defined as the percentage of participants achieving a ≥4-point improvement (reduction) in Worst-Itch Numeric Rating Scale (WI-NRS) score from baseline. The WI-NRS is a patient-reported outcome comprised of a single item rated on a scale from 0 ("no itch") to 10 ("worst imaginable itch"). Participants assessed their worst level of prurigo nodularis-related itch during the past 24 hours on a scale of 0 to 10. The WI-NRS score for baseline was determined by averaging the 7 daily WI-NRS scores before Day 1 (i.e., Days -7 to -1) for all by-visit summaries. The by-visit WI-NRS score for post-baseline visits was determined by averaging the 7 daily WI-NRS scores before the visit day. Participants with missing Week 12 data for any reason, including treatment discontinuation (due to development of atopic dermatitis lesions or any other cause), were defined as nonresponders.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

204 participants

Primary outcome timeframe

Baseline; Week 12

Results posted on

2025-11-14

Participant Flow

Data collected through a cut off date of 7 October 2024 have been included in this summary. Participants were enrolled at 52 sites in Argentina, Belgium, Canada, Chile, France, Germany, Italy, Netherlands, Poland, Spain, and the United States.

Participant milestones

Participant milestones
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
12-week DBVC Period STARTED	103	101
12-week DBVC Period COMPLETED	84	90
12-week DBVC Period NOT COMPLETED	19	11
40-week OLE Period STARTED	84	90
40-week OLE Period COMPLETED	25	20
40-week OLE Period NOT COMPLETED	59	70

Reasons for withdrawal

Reasons for withdrawal
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
12-week DBVC Period Adverse Event	4	1
12-week DBVC Period Physician Decision	1	1
12-week DBVC Period Protocol Violation	4	2
12-week DBVC Period Withdrawal by Subject	9	7
12-week DBVC Period Sponsor Decision	1	0
40-week OLE Period Adverse Event	0	2
40-week OLE Period Lack of Efficacy	1	1
40-week OLE Period Lost to Follow-up	1	0
40-week OLE Period Physician Decision	1	1
40-week OLE Period Protocol Violation	1	1
40-week OLE Period Withdrawal by Subject	6	6
40-week OLE Period Sponsor Decision	3	0
40-week OLE Period Did Not Complete Safety Follow-up Period	0	1
40-week OLE Period Ongoing	46	58

Baseline Characteristics

A Study to Evaluate the Safety and Efficacy of Ruxolitinib Cream in Participants With Prurigo Nodularis (PN)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=103 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Total n=204 Participants Total of all reporting groups
Age, Continuous	61.0 years STANDARD_DEVIATION 13.85 • n=10 Participants	59.1 years STANDARD_DEVIATION 13.78 • n=10 Participants	60.1 years STANDARD_DEVIATION 13.81 • n=20 Participants
Sex: Female, Male Female	65 Participants n=10 Participants	64 Participants n=10 Participants	129 Participants n=20 Participants
Sex: Female, Male Male	38 Participants n=10 Participants	37 Participants n=10 Participants	75 Participants n=20 Participants
Race/Ethnicity, Customized White/Caucasian	84 Participants n=10 Participants	87 Participants n=10 Participants	171 Participants n=20 Participants
Race/Ethnicity, Customized Black or African American	9 Participants n=10 Participants	7 Participants n=10 Participants	16 Participants n=20 Participants
Race/Ethnicity, Customized Asian and Others	9 Participants n=10 Participants	5 Participants n=10 Participants	14 Participants n=20 Participants
Race/Ethnicity, Customized Missing	1 Participants n=10 Participants	2 Participants n=10 Participants	3 Participants n=20 Participants
Race/Ethnicity, Customized Hispanic or Latino	14 Participants n=10 Participants	18 Participants n=10 Participants	32 Participants n=20 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	88 Participants n=10 Participants	80 Participants n=10 Participants	168 Participants n=20 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=10 Participants	1 Participants n=10 Participants	1 Participants n=20 Participants

PRIMARY outcome

Timeframe: Baseline; Week 12

Population: Intent-to-Treat (ITT) Population: all randomized participants. Treatment groups were defined according to the treatment assignment at the time of randomization regardless of the actual study cream the participant might have applied during their participation in the double-blind, vehicle-controlled period. Participants with a baseline ITCH Score ≥4 were analyzed.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=102 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
WI-NRS4 Response at Week 12	20.6 percentage of participants Interval 13.2 to 29.7	44.6 percentage of participants Interval 34.7 to 54.8

SECONDARY outcome

Timeframe: Baseline; Week 4

Population: ITT Population. Participants with a baseline ITCH Score ≥4 were analyzed. Participants with missing Week 4 data for any reason, including treatment discontinuation (due to development of atopic dermatitis lesions or any other cause), were defined as nonresponders.

WI-NRS4 was defined as the percentage of participants achieving a ≥4-point improvement (reduction) in WI-NRS score from baseline. The WI-NRS is a patient-reported outcome comprised of a single item rated on a scale from 0 ("no itch") to 10 ("worst imaginable itch"). Participants assessed their worst level of prurigo nodularis-related itch during the past 24 hours on a scale of 0 to 10. The WI-NRS score for baseline was determined by averaging the 7 daily WI-NRS scores before Day 1 (i.e., Days -7 to -1) for all by-visit summaries. The by-visit WI-NRS score for post-baseline visits was determined by averaging the 7 daily WI-NRS scores before the visit day.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=102 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
WI-NRS4 Response at Week 4	12.7 percentage of participants Interval 7.0 to 20.8	29.7 percentage of participants Interval 21.0 to 39.6

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: ITT Population. Participants with missing Week 12 data for any reason, including treatment discontinuation (due to development of atopic dermatitis lesions or any other cause), were defined as nonresponders.

Overall-Treatment Success was defined as both a WI-NRS4 response and Investigator's Global Assessment for Stage of Chronic Prurigo Treatment Success (IGA-CPG-S-TS). IGA-CPG-S-TS was defined as an IGA-CPG-S score of 0 or 1 with a ≥2 grade improvement from baseline. The IGA-CPG-S is an overall severity rating of chronic prurigo on a scale of 0 to 4: 0, clear (no pruriginous lesions); 1, almost clear (rare palpable pruriginous lesions \[approximately 1-5 lesions\]); 2, mild (few palpable pruriginous lesions \[approximately 6-19 lesions\]); 3, moderate (many palpable pruriginous lesions \[approximately 20-100 lesions\]); 4, severe (abundant palpable pruriginous lesions \[over 100 lesions\]).

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=103 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
Percentage of Participants With Overall-Treatment Success at Week 12	2.9 percentage of participants Interval 0.6 to 8.3	11.9 percentage of participants Interval 6.3 to 19.8

SECONDARY outcome

Timeframe: Baseline; Week 12

IGA-CPG-S-TS was defined as an IGA-CPG-S score of 0 or 1 with a ≥2 grade improvement from baseline. The IGA-CPG-S is an overall severity rating of chronic prurigo on a scale of 0 to 4: 0, clear (no lesions); 1, almost clear (rare palpable pruriginous lesions \[approximately 1-5 lesions\]); 2, mild (few palpable pruriginous lesions \[approximately 6-19 lesions\]); 3, moderate (many palpable pruriginous lesions \[approximately 20-100 lesions\]); 4, severe (abundant palpable pruriginous lesions \[over 100 lesions\]).

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=103 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
Percentage of Participants With IGA-CPG-S-TS at Week 12	3.9 percentage of participants Interval 1.1 to 9.6	15.8 percentage of participants Interval 9.3 to 24.4

SECONDARY outcome

Timeframe: Baseline; Day 7

Population: ITT Population. Participants with a baseline ITCH Score ≥4 were analyzed. Participants with missing Day 7 data for any reason, including treatment discontinuation (due to development of atopic dermatitis lesions or any other cause), were defined as nonresponders.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=102 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
WI-NRS4 Response on Day 7	8.9 percentage of participants Interval 3.9 to 16.8	23.3 percentage of participants Interval 15.1 to 33.4

SECONDARY outcome

Timeframe: Baseline; up to Week 12

Population: ITT Population. Only participants with available data were analyzed.

The WI-NRS is a patient-reported outcome comprised of a single item rated on a scale from 0 ("no itch") to 10 ("worst imaginable itch"). Participants assessed their worst level of prurigo nodularis-related itch during the past 24 hours on a scale of 0 to 10. The WI-NRS score for baseline was determined by averaging the 7 daily WI-NRS scores before Day 1 (i.e., Days -7 to -1) for all by-visit summaries. The by-visit WI-NRS score for post-baseline visits was determined by averaging the 7 daily WI-NRS scores before the visit day.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=103 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
DBVC Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 2	-1.08 scores on a scale Standard Error 0.196	-2.07 scores on a scale Standard Error 0.199
DBVC Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 4	-1.52 scores on a scale Standard Error 0.247	-2.94 scores on a scale Standard Error 0.250
DBVC Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 8	-1.89 scores on a scale Standard Error 0.267	-3.58 scores on a scale Standard Error 0.267
DBVC Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 12	-2.13 scores on a scale Standard Error 0.273	-3.80 scores on a scale Standard Error 0.272

SECONDARY outcome

Timeframe: Baseline; up to Week 52

Population: Open-label Extension Population: all participants who applied ruxolitinib 1.5% cream at least once during the OLE Period. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=84 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=90 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
OLE Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 52	-5.36 scores on a scale Standard Deviation 2.546	-5.03 scores on a scale Standard Deviation 2.548
OLE Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 14	-3.11 scores on a scale Standard Deviation 2.526	-4.45 scores on a scale Standard Deviation 2.679
OLE Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 16	-3.53 scores on a scale Standard Deviation 2.640	-4.41 scores on a scale Standard Deviation 2.742
OLE Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 20	-4.14 scores on a scale Standard Deviation 2.521	-4.58 scores on a scale Standard Deviation 2.701
OLE Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 24	-4.12 scores on a scale Standard Deviation 2.650	-4.64 scores on a scale Standard Deviation 2.543
OLE Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 28	-4.03 scores on a scale Standard Deviation 2.643	-4.66 scores on a scale Standard Deviation 2.614
OLE Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 32	-4.37 scores on a scale Standard Deviation 2.735	-5.40 scores on a scale Standard Deviation 2.538
OLE Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 36	-4.70 scores on a scale Standard Deviation 2.808	-4.86 scores on a scale Standard Deviation 2.784
OLE Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 40	-4.78 scores on a scale Standard Deviation 2.777	-4.43 scores on a scale Standard Deviation 2.794
OLE Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 44	-5.50 scores on a scale Standard Deviation 2.496	-4.81 scores on a scale Standard Deviation 2.538
OLE Period: Change From Baseline in WI-NRS Score at Each Post-baseline Visit Change from Baseline at Week 48	-5.22 scores on a scale Standard Deviation 2.501	-4.78 scores on a scale Standard Deviation 2.914

SECONDARY outcome

Timeframe: Baseline; up to Week 52

Population: ITT Population. Participants with a baseline ITCH Score ≥4 were analyzed. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=102 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
WI-NRS4 Response at Each Post-baseline Visit Week 2	5.2 percentage of participants Interval 1.7 to 11.7	22.2 percentage of participants Interval 14.1 to 32.2
WI-NRS4 Response at Each Post-baseline Visit Week 4	13.8 percentage of participants Interval 7.6 to 22.5	34.5 percentage of participants Interval 24.6 to 45.4
WI-NRS4 Response at Each Post-baseline Visit Week 8	22.1 percentage of participants Interval 13.4 to 33.0	48.8 percentage of participants Interval 37.7 to 60.0
WI-NRS4 Response at Each Post-baseline Visit Week 12	25.9 percentage of participants Interval 16.8 to 36.9	52.3 percentage of participants Interval 41.3 to 63.2
WI-NRS4 Response at Each Post-baseline Visit Week 14	33.8 percentage of participants Interval 23.2 to 45.7	56.8 percentage of participants Interval 45.3 to 67.8
WI-NRS4 Response at Each Post-baseline Visit Week 16	42.7 percentage of participants Interval 31.3 to 54.6	56.8 percentage of participants Interval 44.7 to 68.2
WI-NRS4 Response at Each Post-baseline Visit Week 20	54.2 percentage of participants Interval 42.0 to 66.0	58.6 percentage of participants Interval 46.2 to 70.2
WI-NRS4 Response at Each Post-baseline Visit Week 24	55.7 percentage of participants Interval 43.3 to 67.6	60.8 percentage of participants Interval 48.8 to 72.0
WI-NRS4 Response at Each Post-baseline Visit Week 28	54.7 percentage of participants Interval 41.7 to 67.2	64.2 percentage of participants Interval 51.5 to 75.5
WI-NRS4 Response at Each Post-baseline Visit Week 32	58.7 percentage of participants Interval 43.2 to 73.0	73.5 percentage of participants Interval 58.9 to 85.1
WI-NRS4 Response at Each Post-baseline Visit Week 36	69.8 percentage of participants Interval 53.9 to 82.8	72.5 percentage of participants Interval 56.1 to 85.4
WI-NRS4 Response at Each Post-baseline Visit Week 40	64.9 percentage of participants Interval 47.5 to 79.8	62.1 percentage of participants Interval 42.3 to 79.3
WI-NRS4 Response at Each Post-baseline Visit Week 44	77.8 percentage of participants Interval 57.7 to 91.4	68.0 percentage of participants Interval 46.5 to 85.1
WI-NRS4 Response at Each Post-baseline Visit Week 48	75.0 percentage of participants Interval 53.3 to 90.2	63.2 percentage of participants Interval 38.4 to 83.7
WI-NRS4 Response at Each Post-baseline Visit Week 52	73.9 percentage of participants Interval 51.6 to 89.8	73.7 percentage of participants Interval 48.8 to 90.9

SECONDARY outcome

Timeframe: Baseline; up to Week 52

Population: ITT Population. Participants with a baseline ITCH Score ≥4 were analyzed. Censored participants were included in the analysis.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=102 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
Time to ≥2-point Improvement From Baseline in WI-NRS Score	13.0 days Interval 7.0 to 24.0	5.0 days Interval 4.0 to 8.0

SECONDARY outcome

Timeframe: Baseline; up to Week 52

Population: ITT Population. Participants with a baseline ITCH Score ≥4 were analyzed. Censored participants were included in the analysis.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=102 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
Time to ≥4-point Improvement From Baseline in WI-NRS Score	NA days Interval 60.0 to The median and the upper limit of the confidence interval were not estimable because too few participants had events.	26.0 days Interval 18.0 to 39.0

SECONDARY outcome

Timeframe: Baseline; up to Week 12

Population: ITT Population. Participants with a baseline Skin Pain NRS score ≥2 and available data were analyzed.

Participants assessed their worst level of prurigo nodularis-related skin pain during the past 24 hours on a scale of 0 ("no pain") to 10 ("worse imaginable pain"). The Skin Pain NRS score for baseline was determined by averaging the 7 daily NRS scores before Day 1 (i.e., Days -7 to -1) for all by-visit summaries. The by-visit Skin Pain NRS score for post-baseline visits was determined by averaging the 7 daily NRS scores before the visit day.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=94 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=94 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
DBVC Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 2	20.2 percentage of participants Interval 12.4 to 30.1	36.1 percentage of participants Interval 25.9 to 47.4
DBVC Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 4	30.7 percentage of participants Interval 21.3 to 41.4	56.3 percentage of participants Interval 44.7 to 67.3
DBVC Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 8	33.8 percentage of participants Interval 23.0 to 46.0	64.9 percentage of participants Interval 53.2 to 75.5
DBVC Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 12	45.3 percentage of participants Interval 33.8 to 57.3	65.8 percentage of participants Interval 54.3 to 76.1

SECONDARY outcome

Timeframe: Baseline; up to Week 52

Population: Open-label Extension Population. Participants with a baseline Skin Pain NRS score ≥2 and available data were analyzed.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=76 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=78 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
OLE Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 14	57.1 percentage of participants Interval 44.7 to 68.9	77.3 percentage of participants Interval 66.2 to 86.2
OLE Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 16	68.6 percentage of participants Interval 56.4 to 79.1	79.1 percentage of participants Interval 67.4 to 88.1
OLE Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 20	78.8 percentage of participants Interval 67.0 to 87.9	78.1 percentage of participants Interval 66.0 to 87.5
OLE Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 24	76.9 percentage of participants Interval 64.8 to 86.5	80.9 percentage of participants Interval 69.5 to 89.4
OLE Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 28	72.9 percentage of participants Interval 59.7 to 83.6	82.3 percentage of participants Interval 70.5 to 90.8
OLE Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 32	75.6 percentage of participants Interval 59.7 to 87.6	86.4 percentage of participants Interval 72.6 to 94.8
OLE Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 36	77.5 percentage of participants Interval 61.5 to 89.2	83.8 percentage of participants Interval 68.0 to 93.8
OLE Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 40	85.7 percentage of participants Interval 69.7 to 95.2	80.8 percentage of participants Interval 60.6 to 93.4
OLE Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 44	92.0 percentage of participants Interval 74.0 to 99.0	81.8 percentage of participants Interval 59.7 to 94.8
OLE Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 48	90.9 percentage of participants Interval 70.8 to 98.9	76.5 percentage of participants Interval 50.1 to 93.2
OLE Period: Percentage of Participants With a ≥2-point Improvement (Reduction) in Skin Pain NRS Score From Baseline Week 52	90.5 percentage of participants Interval 69.6 to 98.8	83.3 percentage of participants Interval 58.6 to 96.4

SECONDARY outcome

Timeframe: Baseline; up to Week 12

Population: ITT Population. Analysis was conducted per the MMRM model: (Response Variable = Treatment + Stratification Factors \[IGA-CPG-S/Region\] + Visit + Treatment\*Visit). Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=103 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
DBVC Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 2	-1.02 scores on a scale Standard Error 0.187	-1.70 scores on a scale Standard Error 0.187
DBVC Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 4	-1.44 scores on a scale Standard Error 0.242	-2.58 scores on a scale Standard Error 0.242
DBVC Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 8	-1.84 scores on a scale Standard Error 0.265	-2.94 scores on a scale Standard Error 0.261
DBVC Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 12	-2.05 scores on a scale Standard Error 0.276	-3.19 scores on a scale Standard Error 0.271

SECONDARY outcome

Timeframe: Baseline; up to Week 52

Population: Open-label Extension Population. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=84 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=90 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
OLE Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 14	-2.88 scores on a scale Standard Deviation 2.540	-3.77 scores on a scale Standard Deviation 2.736
OLE Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 16	-3.20 scores on a scale Standard Deviation 2.496	-3.71 scores on a scale Standard Deviation 2.730
OLE Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 20	-3.71 scores on a scale Standard Deviation 2.485	-3.93 scores on a scale Standard Deviation 2.831
OLE Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 24	-3.78 scores on a scale Standard Deviation 2.798	-4.01 scores on a scale Standard Deviation 2.852
OLE Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 28	-3.73 scores on a scale Standard Deviation 2.757	-4.00 scores on a scale Standard Deviation 2.693
OLE Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 32	-3.93 scores on a scale Standard Deviation 2.895	-4.51 scores on a scale Standard Deviation 2.799
OLE Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 36	-4.40 scores on a scale Standard Deviation 2.988	-4.48 scores on a scale Standard Deviation 2.739
OLE Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 40	-4.92 scores on a scale Standard Deviation 2.785	-4.07 scores on a scale Standard Deviation 2.663
OLE Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 44	-5.31 scores on a scale Standard Deviation 2.465	-4.47 scores on a scale Standard Deviation 2.703
OLE Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 48	-5.06 scores on a scale Standard Deviation 2.453	-4.34 scores on a scale Standard Deviation 2.702
OLE Period: Change From Baseline in Skin Pain NRS Score at Each Post-baseline Visit Change from Baseline at Week 52	-4.95 scores on a scale Standard Deviation 2.628	-4.56 scores on a scale Standard Deviation 2.383

SECONDARY outcome

Timeframe: Baseline; up to Week 52

Population: ITT Population. Only participants with available data were analyzed.

IGA-CPG-S-TS was defined as an IGA-CPG-S score of 0 or 1 with a ≥2 grade improvement from baseline. The IGA-CPG-S is an overall severity rating of chronic prurigo nodularis on a scale of 0 to 4: 0, clear (no lesions); 1, almost clear (rare palpable pruriginous lesions \[approximately 1-5 lesions\]); 2, mild (few palpable pruriginous lesions \[approximately 6-19 lesions\]); 3, moderate (many palpable pruriginous lesions \[approximately 20-100 lesions\]); 4, severe (abundant palpable pruriginous lesions \[over 100 lesions\]). Participants with missing Week 12 data for any reason, including treatment discontinuation (due to development of atopic dermatitis lesions or any other cause), were defined as nonresponders.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=103 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 2	1.0 percentage of participants Interval 0.0 to 5.6	2.1 percentage of participants Interval 0.3 to 7.3
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 4	3.2 percentage of participants Interval 0.7 to 9.0	8.4 percentage of participants Interval 3.7 to 15.9
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 8	5.8 percentage of participants Interval 1.9 to 13.0	15.6 percentage of participants Interval 8.8 to 24.7
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 12	4.8 percentage of participants Interval 1.3 to 11.7	17.8 percentage of participants Interval 10.5 to 27.3
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 14	7.6 percentage of participants Interval 2.8 to 15.8	23.0 percentage of participants Interval 14.6 to 33.2
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 16	17.5 percentage of participants Interval 9.9 to 27.6	29.8 percentage of participants Interval 20.3 to 40.7
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 20	22.1 percentage of participants Interval 13.4 to 33.0	30.5 percentage of participants Interval 20.8 to 41.6
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 24	22.4 percentage of participants Interval 13.6 to 33.4	32.5 percentage of participants Interval 22.4 to 43.9
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 28	25.4 percentage of participants Interval 15.8 to 37.1	32.4 percentage of participants Interval 22.0 to 44.3
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 32	32.0 percentage of participants Interval 19.5 to 46.7	36.4 percentage of participants Interval 23.8 to 50.4
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 36	34.1 percentage of participants Interval 20.5 to 49.9	39.1 percentage of participants Interval 25.1 to 54.6
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 40	33.3 percentage of participants Interval 19.1 to 50.2	40.0 percentage of participants Interval 23.9 to 57.9
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 44	43.3 percentage of participants Interval 25.5 to 62.6	42.9 percentage of participants Interval 24.5 to 62.8
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 48	44.0 percentage of participants Interval 24.4 to 65.1	28.6 percentage of participants Interval 11.3 to 52.2
Percentage of Participants With IGA-CPG-S-TS at Each Postbaseline Visit Week 52	50.0 percentage of participants Interval 29.1 to 70.9	40.0 percentage of participants Interval 19.1 to 63.9

SECONDARY outcome

Timeframe: Baseline; up to Week 52

Population: ITT Population. Only participants with available data were analyzed.

The Investigator Global Assessment for Activity of Chronic Prurigo (IGA-CPG-A) is an overall severity rating of chronic prurigo nodularis on a scale of 0 to 4: 0, clear (no pruriginous lesions have excoriations or crusts); 1, almost clear (very small proportion of pruriginous lesions have excoriations or crusts \[up to approximately 10% of all pruriginous lesions\]); 2, mild (minority of pruriginous lesions have excoriations or crusts \[approximately 11%-25% of all pruriginous lesions\]); 3, moderate (many pruriginous lesions have excoriations or crusts \[approximately 26%-75% of all pruriginous lesions\]); 4, severe (majority of pruriginous lesions have excoriations or crusts \[approximately 76%-100% of all pruriginous lesions\]).

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=103 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 2	1.0 percentage of participants Interval 0.0 to 5.6	5.2 percentage of participants Interval 1.7 to 11.6
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 4	5.3 percentage of participants Interval 1.7 to 12.0	11.6 percentage of participants Interval 5.9 to 19.8
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 8	14.0 percentage of participants Interval 7.4 to 23.1	24.4 percentage of participants Interval 16.0 to 34.6
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 12	10.7 percentage of participants Interval 5.0 to 19.4	23.3 percentage of participants Interval 15.1 to 33.4
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 14	17.7 percentage of participants Interval 10.0 to 27.9	25.3 percentage of participants Interval 16.6 to 35.7
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 16	31.3 percentage of participants Interval 21.3 to 42.6	34.5 percentage of participants Interval 24.5 to 45.7
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 20	26.0 percentage of participants Interval 16.6 to 37.2	35.4 percentage of participants Interval 25.1 to 46.7
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 24	40.8 percentage of participants Interval 29.6 to 52.7	38.8 percentage of participants Interval 28.1 to 50.3
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 28	39.4 percentage of participants Interval 28.0 to 51.7	37.8 percentage of participants Interval 26.8 to 49.9
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 32	36.0 percentage of participants Interval 22.9 to 50.8	38.2 percentage of participants Interval 25.4 to 52.3
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 36	43.2 percentage of participants Interval 28.3 to 59.0	41.3 percentage of participants Interval 27.0 to 56.8
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 40	41.0 percentage of participants Interval 25.6 to 57.9	37.1 percentage of participants Interval 21.5 to 55.1
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 44	53.3 percentage of participants Interval 34.3 to 71.7	50.0 percentage of participants Interval 30.6 to 69.4
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 48	56.0 percentage of participants Interval 34.9 to 75.6	47.6 percentage of participants Interval 25.7 to 70.2
Percentage of Participants With a IGA-CPG-A Score of 0 or 1 With ≥2-grade Improvement (Reduction) at Each Post-baseline Visit Week 52	62.5 percentage of participants Interval 40.6 to 81.2	55.0 percentage of participants Interval 31.5 to 76.9

SECONDARY outcome

Timeframe: Baseline; up to Week 12

Population: ITT Population. Only participants with available data were analyzed.

The extent and severity of prurigo nodularis was assessed via the PAS (version 1.2). The first 3 items are descriptive of the type, predominant type, distribution, and quantity of pruriginous lesions. The remaining 2 items of the PAS assess disease activity in terms of percentage (i.e., 0%, 1%-25%, 26%-50%, 51%-75%, and 76%-100%) of pruriginous lesions with excoriations/crusts on top (to reflect active scratching) and the percentage (i.e., 100%, 76%-99%, 51%-75%, 26%-50%, and 0%-25%) of healed pruriginous lesions in order to quantify change of prurigo nodularis skin lesions.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=103 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
DBVC Period: Percentage of Participants With >75% Healed Lesions From Prurigo Activity Score (PAS) at Each Postbaseline Visit Week 8	23.3 percentage of participants Interval 14.8 to 33.6	32.2 percentage of participants Interval 22.8 to 42.9
DBVC Period: Percentage of Participants With >75% Healed Lesions From Prurigo Activity Score (PAS) at Each Postbaseline Visit Week 12	22.6 percentage of participants Interval 14.2 to 33.0	32.2 percentage of participants Interval 22.8 to 42.9
DBVC Period: Percentage of Participants With >75% Healed Lesions From Prurigo Activity Score (PAS) at Each Postbaseline Visit Week 2	10.3 percentage of participants Interval 5.1 to 18.1	14.4 percentage of participants Interval 8.1 to 23.0
DBVC Period: Percentage of Participants With >75% Healed Lesions From Prurigo Activity Score (PAS) at Each Postbaseline Visit Week 4	21.3 percentage of participants Interval 13.5 to 30.9	26.3 percentage of participants Interval 17.8 to 36.4

SECONDARY outcome

Timeframe: Baseline; up to Week 52

Population: Open-label Extension Population. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=84 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=90 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
OLE Period: Percentage of Participants With >75% Healed Lesions From PAS at Each Postbaseline Visit Week 14	36.7 percentage of participants Interval 26.1 to 48.3	37.9 percentage of participants Interval 27.7 to 49.0
OLE Period: Percentage of Participants With >75% Healed Lesions From PAS at Each Postbaseline Visit Week 16	40.0 percentage of participants Interval 29.2 to 51.6	45.2 percentage of participants Interval 34.3 to 56.5
OLE Period: Percentage of Participants With >75% Healed Lesions From PAS at Each Postbaseline Visit Week 20	45.5 percentage of participants Interval 34.1 to 57.2	45.1 percentage of participants Interval 34.1 to 56.5
OLE Period: Percentage of Participants With >75% Healed Lesions From PAS at Each Postbaseline Visit Week 24	56.6 percentage of participants Interval 44.7 to 67.9	48.8 percentage of participants Interval 37.4 to 60.2
OLE Period: Percentage of Participants With >75% Healed Lesions From PAS at Each Postbaseline Visit Week 28	63.4 percentage of participants Interval 51.1 to 74.5	45.9 percentage of participants Interval 34.3 to 57.9
OLE Period: Percentage of Participants With >75% Healed Lesions From PAS at Each Postbaseline Visit Week 32	64.0 percentage of participants Interval 49.2 to 77.1	50.9 percentage of participants Interval 37.1 to 64.6
OLE Period: Percentage of Participants With >75% Healed Lesions From PAS at Each Postbaseline Visit Week 36	68.2 percentage of participants Interval 52.4 to 81.4	56.5 percentage of participants Interval 41.1 to 71.1
OLE Period: Percentage of Participants With >75% Healed Lesions From PAS at Each Postbaseline Visit Week 40	64.1 percentage of participants Interval 47.2 to 78.8	57.1 percentage of participants Interval 39.4 to 73.7
OLE Period: Percentage of Participants With >75% Healed Lesions From PAS at Each Postbaseline Visit Week 44	73.3 percentage of participants Interval 54.1 to 87.7	64.3 percentage of participants Interval 44.1 to 81.4
OLE Period: Percentage of Participants With >75% Healed Lesions From PAS at Each Postbaseline Visit Week 48	80.0 percentage of participants Interval 59.3 to 93.2	61.9 percentage of participants Interval 38.4 to 81.9
OLE Period: Percentage of Participants With >75% Healed Lesions From PAS at Each Postbaseline Visit Week 52	75.0 percentage of participants Interval 53.3 to 90.2	60.0 percentage of participants Interval 36.1 to 80.9

SECONDARY outcome

Timeframe: Baseline; up to Week 12

Population: ITT Population. Only participants with available data were analyzed.

The DLQI is a simple, 10-question, validated questionnaire to measure how much the skin problem has affected the participant over the previous 7 days. Each question was scored as: 3 (very much), 2 (a lot), 1 (a little), 0 (not at all or not relevant). The DLQI total score was calculated by summing the score of each question, resulting in a maximum of 30 and a minimum of 0. The higher the score, the more the quality of life was impaired. Total DLQI scores were categorized as follows: 0 to 1 (no effect), 2 to 5 (small effect), 6 to 10 (moderate effect), 11 to 20 (very large effect), and 21 to 30 (extremely large effect). Change from Baseline was calculated as the post-baseline visit minus the baseline visit.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=103 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
DBVC Period: Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Each Post-baseline Visit Change from Baseline at Week 2	-4.47 scores on a scale Standard Error 0.591	-4.67 scores on a scale Standard Error 0.576
DBVC Period: Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Each Post-baseline Visit Change from Baseline at Week 4	-5.37 scores on a scale Standard Error 0.661	-5.71 scores on a scale Standard Error 0.650
DBVC Period: Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Each Post-baseline Visit Change from Baseline at Week 8	-5.17 scores on a scale Standard Error 0.677	-6.25 scores on a scale Standard Error 0.661
DBVC Period: Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Each Post-baseline Visit Change from Baseline at Week 12	-4.65 scores on a scale Standard Error 0.696	-6.04 scores on a scale Standard Error 0.675

SECONDARY outcome

Timeframe: Baseline; up to Week 52

Population: Open-label Extension Population. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=84 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=90 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
OLE Period: Change From Baseline in the DLQI Total Score at Each Post-baseline Visit Change from Baseline at Week 14	-7.22 scores on a scale Standard Deviation 6.179	-6.90 scores on a scale Standard Deviation 6.097
OLE Period: Change From Baseline in the DLQI Total Score at Each Post-baseline Visit Change from Baseline at Week 16	-7.27 scores on a scale Standard Deviation 6.210	-7.60 scores on a scale Standard Deviation 5.979
OLE Period: Change From Baseline in the DLQI Total Score at Each Post-baseline Visit Change from Baseline at Week 20	-6.97 scores on a scale Standard Deviation 6.158	-6.98 scores on a scale Standard Deviation 6.084
OLE Period: Change From Baseline in the DLQI Total Score at Each Post-baseline Visit Change from Baseline at Week 24	-6.88 scores on a scale Standard Deviation 5.421	-7.28 scores on a scale Standard Deviation 6.088
OLE Period: Change From Baseline in the DLQI Total Score at Each Post-baseline Visit Change from Baseline at Week 28	-7.29 scores on a scale Standard Deviation 6.018	-7.25 scores on a scale Standard Deviation 5.845
OLE Period: Change From Baseline in the DLQI Total Score at Each Post-baseline Visit Change from Baseline at Week 32	-7.06 scores on a scale Standard Deviation 5.363	-7.79 scores on a scale Standard Deviation 6.188
OLE Period: Change From Baseline in the DLQI Total Score at Each Post-baseline Visit Change from Baseline at Week 36	-6.61 scores on a scale Standard Deviation 5.004	-7.74 scores on a scale Standard Deviation 6.207
OLE Period: Change From Baseline in the DLQI Total Score at Each Post-baseline Visit Change from Baseline at Week 40	-6.62 scores on a scale Standard Deviation 4.663	-6.61 scores on a scale Standard Deviation 5.963
OLE Period: Change From Baseline in the DLQI Total Score at Each Post-baseline Visit Change from Baseline at Week 44	-6.41 scores on a scale Standard Deviation 4.179	-6.56 scores on a scale Standard Deviation 5.094
OLE Period: Change From Baseline in the DLQI Total Score at Each Post-baseline Visit Change from Baseline at Week 48	-4.96 scores on a scale Standard Deviation 4.704	-6.30 scores on a scale Standard Deviation 4.846
OLE Period: Change From Baseline in the DLQI Total Score at Each Post-baseline Visit Change from Baseline at Week 52	-5.95 scores on a scale Standard Deviation 4.146	-6.53 scores on a scale Standard Deviation 5.521

SECONDARY outcome

Timeframe: Baseline; up to Week 12

Population: ITT Population. Only participants with available data were analyzed.

The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L consists of 2 sections: the EQ-5D descriptive system and the EQ VAS. The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ VAS records the participant's self-rated health on a vertical VAS (0-100), on which the endpoints are labeled "the best health you can imagine" (100 score) and "the worst health you can imagine" (0 score). Change from Baseline was calculated as the post-baseline value minus the baseline value.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=103 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
DBVC Period: Change From Baseline in European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) Visual Analog Scale (VAS) Score at Each Postbaseline Visit Change from Baseline at Week 2	3.00 scores on a scale Standard Error 1.948	7.90 scores on a scale Standard Error 1.896
DBVC Period: Change From Baseline in European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) Visual Analog Scale (VAS) Score at Each Postbaseline Visit Change from Baseline at Week 4	5.59 scores on a scale Standard Error 1.940	8.90 scores on a scale Standard Error 1.914
DBVC Period: Change From Baseline in European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) Visual Analog Scale (VAS) Score at Each Postbaseline Visit Change from Baseline at Week 8	2.52 scores on a scale Standard Error 2.189	9.83 scores on a scale Standard Error 2.133
DBVC Period: Change From Baseline in European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) Visual Analog Scale (VAS) Score at Each Postbaseline Visit Change from Baseline at Week 12	5.35 scores on a scale Standard Error 2.235	11.26 scores on a scale Standard Error 2.171

SECONDARY outcome

Timeframe: Baseline; up to Week 52

Population: Open-label Extension Population. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=84 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=90 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
OLE Period: Change From Baseline in EQ-5D-5L VAS Score at Each Postbaseline Visit Change from Baseline at Week 14	7.54 scores on a scale Standard Deviation 19.216	10.49 scores on a scale Standard Deviation 19.469
OLE Period: Change From Baseline in EQ-5D-5L VAS Score at Each Postbaseline Visit Change from Baseline at Week 16	6.06 scores on a scale Standard Deviation 20.263	12.06 scores on a scale Standard Deviation 18.268
OLE Period: Change From Baseline in EQ-5D-5L VAS Score at Each Postbaseline Visit Change from Baseline at Week 20	8.51 scores on a scale Standard Deviation 18.617	12.34 scores on a scale Standard Deviation 20.446
OLE Period: Change From Baseline in EQ-5D-5L VAS Score at Each Postbaseline Visit Change from Baseline at Week 24	10.12 scores on a scale Standard Deviation 17.469	11.61 scores on a scale Standard Deviation 19.913
OLE Period: Change From Baseline in EQ-5D-5L VAS Score at Each Postbaseline Visit Change from Baseline at Week 28	10.24 scores on a scale Standard Deviation 17.467	12.86 scores on a scale Standard Deviation 19.851
OLE Period: Change From Baseline in EQ-5D-5L VAS Score at Each Postbaseline Visit Change from Baseline at Week 32	8.43 scores on a scale Standard Deviation 14.200	14.19 scores on a scale Standard Deviation 18.760
OLE Period: Change From Baseline in EQ-5D-5L VAS Score at Each Postbaseline Visit Change from Baseline at Week 36	9.85 scores on a scale Standard Deviation 15.779	13.58 scores on a scale Standard Deviation 16.684
OLE Period: Change From Baseline in EQ-5D-5L VAS Score at Each Postbaseline Visit Change from Baseline at Week 40	5.95 scores on a scale Standard Deviation 13.603	14.94 scores on a scale Standard Deviation 16.165
OLE Period: Change From Baseline in EQ-5D-5L VAS Score at Each Postbaseline Visit Change from Baseline at Week 44	6.62 scores on a scale Standard Deviation 14.027	11.81 scores on a scale Standard Deviation 16.948
OLE Period: Change From Baseline in EQ-5D-5L VAS Score at Each Postbaseline Visit Change from Baseline at Week 48	7.33 scores on a scale Standard Deviation 14.288	6.65 scores on a scale Standard Deviation 14.929
OLE Period: Change From Baseline in EQ-5D-5L VAS Score at Each Postbaseline Visit Change from Baseline at Week 52	10.32 scores on a scale Standard Deviation 8.676	8.89 scores on a scale Standard Deviation 11.338

SECONDARY outcome

Timeframe: Baseline; up to Week 12

Population: ITT Population. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=103 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=101 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 2, Mobility	-0.18 scores on a scale Standard Deviation 0.912	-0.07 scores on a scale Standard Deviation 0.606
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 4, Mobility	-0.21 scores on a scale Standard Deviation 0.742	-0.08 scores on a scale Standard Deviation 0.810
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 8, Mobility	-0.19 scores on a scale Standard Deviation 0.813	-0.08 scores on a scale Standard Deviation 0.690
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 12, Mobility	-0.13 scores on a scale Standard Deviation 0.973	-0.14 scores on a scale Standard Deviation 0.714
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 2, Self-care	-0.01 scores on a scale Standard Deviation 0.533	-0.05 scores on a scale Standard Deviation 0.533
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 4, Self-care	-0.06 scores on a scale Standard Deviation 0.505	-0.07 scores on a scale Standard Deviation 0.493
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 8, Self-care	-0.06 scores on a scale Standard Deviation 0.581	-0.06 scores on a scale Standard Deviation 0.581
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 12, Self-care	0.03 scores on a scale Standard Deviation 0.636	-0.06 scores on a scale Standard Deviation 0.488
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 2, Usual activities	-0.19 scores on a scale Standard Deviation 0.782	-0.25 scores on a scale Standard Deviation 0.714
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 4, Usual activities	-0.11 scores on a scale Standard Deviation 0.785	-0.21 scores on a scale Standard Deviation 0.727
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 8, Usual activities	-0.23 scores on a scale Standard Deviation 0.811	-0.22 scores on a scale Standard Deviation 0.726
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 12, Usual activities	-0.05 scores on a scale Standard Deviation 0.727	-0.27 scores on a scale Standard Deviation 0.723
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 2, Pain/discomfort	-0.42 scores on a scale Standard Deviation 1.136	-0.56 scores on a scale Standard Deviation 0.953
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 4, Pain/discomfort	-0.67 scores on a scale Standard Deviation 1.132	-0.67 scores on a scale Standard Deviation 1.039
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 8, Pain/discomfort	-0.56 scores on a scale Standard Deviation 1.112	-0.66 scores on a scale Standard Deviation 1.080
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 12, Pain/discomfort	-0.54 scores on a scale Standard Deviation 1.078	-0.70 scores on a scale Standard Deviation 1.074
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 2, Anxiety/depression	-0.20 scores on a scale Standard Deviation 1.013	-0.24 scores on a scale Standard Deviation 0.919
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 4, Anxiety/depression	-0.28 scores on a scale Standard Deviation 1.102	-0.34 scores on a scale Standard Deviation 0.996
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 8, Anxiety/depression	-0.19 scores on a scale Standard Deviation 1.045	-0.37 scores on a scale Standard Deviation 0.934
DBVC Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 12, Anxiety/depression	-0.24 scores on a scale Standard Deviation 1.105	-0.32 scores on a scale Standard Deviation 0.941

SECONDARY outcome

Timeframe: Baseline; up to Week 52

Population: Open-label Extension Population. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=84 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=90 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 44, Pain/discomfort	-1.00 scores on a scale Standard Deviation 1.000	-0.78 scores on a scale Standard Deviation 1.121
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 48, Pain/discomfort	-0.83 scores on a scale Standard Deviation 0.963	-0.80 scores on a scale Standard Deviation 1.105
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 52, Pain/discomfort	-0.95 scores on a scale Standard Deviation 0.999	-0.84 scores on a scale Standard Deviation 1.015
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 14, Anxiety/depression	-0.25 scores on a scale Standard Deviation 1.179	-0.37 scores on a scale Standard Deviation 1.030
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 16, Anxiety/depression	-0.35 scores on a scale Standard Deviation 1.167	-0.48 scores on a scale Standard Deviation 0.972
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 20, Anxiety/depression	-0.30 scores on a scale Standard Deviation 0.961	-0.38 scores on a scale Standard Deviation 0.933
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 24, Anxiety/depression	-0.30 scores on a scale Standard Deviation 0.953	-0.33 scores on a scale Standard Deviation 0.890
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 28, Anxiety/depression	-0.26 scores on a scale Standard Deviation 0.924	-0.28 scores on a scale Standard Deviation 0.897
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 32, Anxiety/depression	-0.28 scores on a scale Standard Deviation 0.800	-0.38 scores on a scale Standard Deviation 0.867
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 36, Anxiety/depression	-0.17 scores on a scale Standard Deviation 0.892	-0.63 scores on a scale Standard Deviation 0.952
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 40, Anxiety/depression	-0.27 scores on a scale Standard Deviation 0.732	-0.55 scores on a scale Standard Deviation 0.905
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 44, Anxiety/depression	-0.21 scores on a scale Standard Deviation 0.940	-0.33 scores on a scale Standard Deviation 1.038
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 48, Anxiety/depression	-0.04 scores on a scale Standard Deviation 0.806	-0.15 scores on a scale Standard Deviation 0.933
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 52, Anxiety/depression	-0.27 scores on a scale Standard Deviation 0.767	-0.32 scores on a scale Standard Deviation 0.749
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 14, Mobility	-0.05 scores on a scale Standard Deviation 0.728	-0.10 scores on a scale Standard Deviation 0.882
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 16, Mobility	-0.17 scores on a scale Standard Deviation 0.657	-0.11 scores on a scale Standard Deviation 0.786
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 20, Mobility	-0.22 scores on a scale Standard Deviation 0.798	-0.19 scores on a scale Standard Deviation 0.748
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 24, Mobility	-0.27 scores on a scale Standard Deviation 0.886	-0.12 scores on a scale Standard Deviation 0.697
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 28, Mobility	-0.10 scores on a scale Standard Deviation 0.917	-0.15 scores on a scale Standard Deviation 0.856
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 32, Mobility	-0.09 scores on a scale Standard Deviation 0.974	-0.25 scores on a scale Standard Deviation 0.926
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 36, Mobility	-0.15 scores on a scale Standard Deviation 0.963	-0.16 scores on a scale Standard Deviation 0.843
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 40, Mobility	-0.24 scores on a scale Standard Deviation 0.830	-0.12 scores on a scale Standard Deviation 0.740
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 44, Mobility	-0.14 scores on a scale Standard Deviation 0.833	0.07 scores on a scale Standard Deviation 0.829
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 48, Mobility	-0.08 scores on a scale Standard Deviation 0.974	-0.05 scores on a scale Standard Deviation 0.999
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 52, Mobility	-0.23 scores on a scale Standard Deviation 0.869	0.05 scores on a scale Standard Deviation 0.970
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 14, Self-care	0.04 scores on a scale Standard Deviation 0.552	0.02 scores on a scale Standard Deviation 0.613
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 16, Self-care	0.00 scores on a scale Standard Deviation 0.562	-0.11 scores on a scale Standard Deviation 0.521
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 20, Self-care	0.05 scores on a scale Standard Deviation 0.521	-0.06 scores on a scale Standard Deviation 0.486
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 24, Self-care	-0.04 scores on a scale Standard Deviation 0.455	0.00 scores on a scale Standard Deviation 0.465
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 28, Self-care	-0.04 scores on a scale Standard Deviation 0.438	-0.10 scores on a scale Standard Deviation 0.452
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 32, Self-care	-0.09 scores on a scale Standard Deviation 0.351	0.00 scores on a scale Standard Deviation 0.280
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 36, Self-care	-0.05 scores on a scale Standard Deviation 0.384	-0.02 scores on a scale Standard Deviation 0.266
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 40, Self-care	-0.03 scores on a scale Standard Deviation 0.287	0.00 scores on a scale Standard Deviation 0.000
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 44, Self-care	0.00 scores on a scale Standard Deviation 0.267	0.00 scores on a scale Standard Deviation 0.277
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 48, Self-care	-0.04 scores on a scale Standard Deviation 0.204	-0.05 scores on a scale Standard Deviation 0.224
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 52, Self-care	0.05 scores on a scale Standard Deviation 0.375	-0.05 scores on a scale Standard Deviation 0.229
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 14, Usual activities	-0.13 scores on a scale Standard Deviation 0.838	-0.22 scores on a scale Standard Deviation 0.773
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 16, Usual activities	-0.21 scores on a scale Standard Deviation 0.800	-0.28 scores on a scale Standard Deviation 0.742
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 20, Usual activities	-0.24 scores on a scale Standard Deviation 0.791	-0.31 scores on a scale Standard Deviation 0.773
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 24, Usual activities	-0.25 scores on a scale Standard Deviation 0.813	-0.21 scores on a scale Standard Deviation 0.643
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 28, Usual activities	-0.21 scores on a scale Standard Deviation 0.783	-0.32 scores on a scale Standard Deviation 0.858
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 32, Usual activities	-0.36 scores on a scale Standard Deviation 0.735	-0.33 scores on a scale Standard Deviation 0.706
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 36, Usual activities	-0.15 scores on a scale Standard Deviation 0.654	-0.28 scores on a scale Standard Deviation 0.630
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 40, Usual activities	-0.16 scores on a scale Standard Deviation 0.602	-0.18 scores on a scale Standard Deviation 0.683
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 44, Usual activities	-0.24 scores on a scale Standard Deviation 0.425	-0.11 scores on a scale Standard Deviation 0.698
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 48, Usual activities	0.04 scores on a scale Standard Deviation 0.550	-0.20 scores on a scale Standard Deviation 0.768
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 52, Usual activities	-0.32 scores on a scale Standard Deviation 0.568	-0.11 scores on a scale Standard Deviation 0.809
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 14, Pain/discomfort	-0.78 scores on a scale Standard Deviation 1.040	-0.67 scores on a scale Standard Deviation 1.057
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 16, Pain/discomfort	-0.86 scores on a scale Standard Deviation 0.969	-0.73 scores on a scale Standard Deviation 1.089
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 20, Pain/discomfort	-0.77 scores on a scale Standard Deviation 0.915	-0.68 scores on a scale Standard Deviation 1.199
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 24, Pain/discomfort	-0.88 scores on a scale Standard Deviation 0.897	-0.81 scores on a scale Standard Deviation 1.062
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 28, Pain/discomfort	-0.90 scores on a scale Standard Deviation 0.964	-0.83 scores on a scale Standard Deviation 0.956
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 32, Pain/discomfort	-0.91 scores on a scale Standard Deviation 0.929	-0.92 scores on a scale Standard Deviation 1.100
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 36, Pain/discomfort	-0.85 scores on a scale Standard Deviation 1.062	-0.95 scores on a scale Standard Deviation 1.090
OLE Period: Change From Baseline in EQ-5D-5L Dimension Scores at Each Postbaseline Visit Change from Baseline at Week 40, Pain/discomfort	-1.05 scores on a scale Standard Deviation 1.104	-0.85 scores on a scale Standard Deviation 1.093

SECONDARY outcome

Timeframe: up to Week 12

Population: Safety Population: all participants who applied ruxolitinib 1.5% cream or vehicle cream at least once. Treatment groups were determined according to the actual treatment the participant applied on Day 1 regardless of assigned treatment group.

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE can therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study cream. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=103 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=100 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
DBVC Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)	37 Participants	31 Participants

SECONDARY outcome

Timeframe: up to Week 12

Population: Safety Population

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE can therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study cream. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug. The severity of TEAEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grades 1 through 5. The investigator made an assessment of intensity for each TEAE and assigned it to one of the following categories: Grade 1, mild; Grade 2, moderate; Grade 3, severe or medically significant but not immediately life threatening; Grade 4, life-threatening consequences; Grade 5, fatal.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=103 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=100 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
DBVC Period: Number of Participants With Any ≥Grade 3 TEAE	5 Participants	4 Participants

SECONDARY outcome

Timeframe: from beginning of Week 13 up to Week 56

Population: Open-label Extension Population

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=84 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=90 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
OLE Period: Number of Participants With Any TEAE	37 Participants	46 Participants

SECONDARY outcome

Timeframe: from beginning of Week 13 up to Week 56

Population: Open-label Extension Population

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE can therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study cream. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug. The severity of TEAEs was assessed using CTCAE version 5.0 Grades 1 through 5. The investigator made an assessment of intensity for each TEAE and assigned it to one of the following categories: Grade 1, mild; Grade 2, moderate; Grade 3, severe or medically significant but not immediately life threatening; Grade 4, life-threatening consequences; Grade 5, fatal.

Outcome measures

Outcome measures
Measure	Vehicle Cream BID to Ruxolitinib 1.5% Cream BID n=84 Participants Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the DBVC Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (IGA-CPG-S score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week OLE extension period. Participants randomized to vehicle cream at baseline switched to ruxolitinib 1.5% cream BID and received treatment through Week 52. During the OLE period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.	Ruxolitinib 1.5% Cream BID to Ruxolitinib 1.5% Cream BID n=90 Participants Participants applied ruxolitinib 1.5% cream twice daily (BID) through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period. At Week 12, the investigator assessed whether the participant required continuation of therapy (Investigator Global Assessment for Stage of Chronic Prurigo \[IGA-CPG-S\] score ≥1 and/or the presence of prurigo nodularis-related itching). Those participants who completed 12 weeks of treatment with no safety concerns were eligible to enter the 40-week Open-label Extension (OLE) period. Participants randomized to ruxolitinib 1.5% cream at baseline remained on ruxolitinib 1.5% cream BID through Week 52. During the OLE Period, participants applied ruxolitinib 1.5% cream BID to prurigo nodularis-affected areas plus an approximate 1 cm area surrounding each pruriginous lesion and/or areas of prurigo nodularis-related itching.
OLE Period: Number of Participants With Any ≥Grade 3 TEAE	5 Participants	6 Participants

Adverse Events

Vehicle Cream BID

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

Ruxolitinib 1.5% Cream BID

Serious events: 13 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Vehicle Cream BID n=103 participants at risk Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period.	Ruxolitinib 1.5% Cream BID n=184 participants at risk Participants applied ruxolitinib 1.5% cream BID to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion for 12 weeks in the DBVC Period and for 40 weeks in the OLE Period. Participants who applied matching vehicle cream BID for 12 weeks during the DBVC Period and completed the Week 12 assessments with no safety concerns applied ruxolitinib 1.5% cream for 40 weeks during the OLE Period.
Infections and infestations COVID-19	3.9% 4/103 • Number of events 4 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	5.4% 10/184 • Number of events 10 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Infections and infestations Nasopharyngitis	1.9% 2/103 • Number of events 2 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	9.2% 17/184 • Number of events 21 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.

Additional Information

Study Director

Incyte Corporation

Phone: 1-855-463-3463

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Vehicle Cream BID n=103 participants at risk Participants applied vehicle cream BID through Week 12 to all pruriginous lesions identified at baseline plus an approximate 1 cm area surrounding each lesion in the Double-blind, Vehicle-controlled (DBVC) Period.	Ruxolitinib 1.5% Cream BID n=184 participants at risk Participants applied ruxolitinib 1.5% cream BID to all pruriginous lesions identified at baseline plus an approximate 1 centimeter (cm) area surrounding each lesion for 12 weeks in the DBVC Period and for 40 weeks in the OLE Period. Participants who applied matching vehicle cream BID for 12 weeks during the DBVC Period and completed the Week 12 assessments with no safety concerns applied ruxolitinib 1.5% cream for 40 weeks during the OLE Period.
Infections and infestations Abscess neck	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Cardiac disorders Atrial flutter	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Injury, poisoning and procedural complications Burns second degree	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Infections and infestations COVID-19	0.97% 1/103 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.00% 0/184 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Cardiac disorders Cardiac failure congestive	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Nervous system disorders Cerebrovascular accident	0.97% 1/103 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.00% 0/184 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Psychiatric disorders Depression	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Skin and subcutaneous tissue disorders Hidradenitis	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Nervous system disorders Ischaemic stroke	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Blood and lymphatic system disorders Lymphadenitis	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Renal and urinary disorders Nephrolithiasis	0.97% 1/103 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Skin and subcutaneous tissue disorders Neurodermatitis	0.97% 1/103 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Psychiatric disorders Panic attack	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Infections and infestations Pneumonia	0.97% 1/103 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Infections and infestations Pulmonary sepsis	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Infections and infestations Urinary tract infection	0.97% 1/103 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.00% 0/184 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.
Ear and labyrinth disorders Vertigo	0.00% 0/103 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.	0.54% 1/184 • Number of events 1 • up to Week 56 For participants who were on vehicle up to Week 12 and then switched to ruxolitinib, adverse events are presented by the treatment they were on at the onset of the event. Data have been presented for the Safety Population, comprised of all participants who applied at least one dose of ruxolitinib 1.5% cream or vehicle cream.