Trial Outcomes & Findings for Proof of Concept Study of Rilzabrutinib in Adult Patients With Moderate-to-severe Atopic Dermatitis (NCT NCT05018806)

Last Updated: 2026-07-13

Results Overview

The EASI index is a validated investigator-administered scoring system used to measure the severity of clinical signs in atopic dermatitis (AD). Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) were each assessed for severity by the investigator or designee on a scale of "0" (absent) through "3" (severe). In addition, the area of AD involvement were assessed as a percentage by body area of head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6. 0: 0% of body surface area (BSA) involvement with AD; 1: 1-9%; 2: 10-29%; 2: 30-49%; 4: 50-69%; 5: 70-89% and 6: 90-100% of BSA involvement with AD. Total score ranged from 0 (minimum) to 72 (maximum); higher scores indicated greater severity of AD. Baseline was defined as the Day 1 assessment value.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

124 participants

Primary outcome timeframe

Baseline (Day 1) to Week 16

Results posted on

2026-07-13

Participant Flow

The study was conducted at 31 centers in 7 countries. 61 participants in twice a day (BID) cohort and 106 participants in three times a day (TID) cohort were screened from 09 September 2021 to 24 February 2023, of which 16 in BID cohort and 27 in TID cohort were screen failures. Screen failures were mainly due to not meeting the eligibility criteria.

A total of 45 participants in BID cohort and 79 participants in TID cohort were randomized in a ratio of 3:2 to receive either rilzabrutinib or matching placebo on Day 1 in the BID and TID cohorts, respectively.

Participant milestones

Participant milestones
Measure	BID Cohort: Placebo Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib 400 mg BID Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib 400 mg TID Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Overall Study STARTED	18	27	31	48
Overall Study COMPLETED	14	23	26	31
Overall Study NOT COMPLETED	4	4	5	17

Reasons for withdrawal

Reasons for withdrawal
Measure	BID Cohort: Placebo Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib 400 mg BID Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib 400 mg TID Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Overall Study Adverse event (AE): Not related to Coronavirus Disease-2019 (COVID-19)	1	1	2	7
Overall Study Withdrawal by Subject	3	3	3	10

Baseline Characteristics

Proof of Concept Study of Rilzabrutinib in Adult Patients With Moderate-to-severe Atopic Dermatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BID Cohort: Placebo n=18 Participants Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib 400 mg BID n=27 Participants Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo n=31 Participants Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib 400 mg TID n=48 Participants Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	Total n=124 Participants Total of all reporting groups
Age, Continuous	33.9 Years STANDARD_DEVIATION 13.0 • n=20 Participants	38.3 Years STANDARD_DEVIATION 16.1 • n=20 Participants	33.1 Years STANDARD_DEVIATION 12.4 • n=40 Participants	36.1 Years STANDARD_DEVIATION 14.1 • n=5 Participants	35.5 Years STANDARD_DEVIATION 14.0 • n=9 Participants
Sex: Female, Male Female	10 Participants n=20 Participants	15 Participants n=20 Participants	15 Participants n=40 Participants	31 Participants n=5 Participants	71 Participants n=9 Participants
Sex: Female, Male Male	8 Participants n=20 Participants	12 Participants n=20 Participants	16 Participants n=40 Participants	17 Participants n=5 Participants	53 Participants n=9 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=20 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=5 Participants	0 Participants n=9 Participants
Race (NIH/OMB) Asian	2 Participants n=20 Participants	2 Participants n=20 Participants	4 Participants n=40 Participants	6 Participants n=5 Participants	14 Participants n=9 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=20 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=5 Participants	0 Participants n=9 Participants
Race (NIH/OMB) Black or African American	0 Participants n=20 Participants	1 Participants n=20 Participants	2 Participants n=40 Participants	4 Participants n=5 Participants	7 Participants n=9 Participants
Race (NIH/OMB) White	16 Participants n=20 Participants	23 Participants n=20 Participants	25 Participants n=40 Participants	38 Participants n=5 Participants	102 Participants n=9 Participants
Race (NIH/OMB) More than one race	0 Participants n=20 Participants	1 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=5 Participants	1 Participants n=9 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=20 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=5 Participants	0 Participants n=9 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Week 16

Population: Intent-to-treat (ITT) population included all randomized participants analyzed according to intervention group allocated by randomization regardless of whether intervention was received or not. Only those participants with data collected at specified timepoints are reported.

Outcome measures

Outcome measures
Measure	BID Cohort: Placebo n=18 Participants Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib n=24 Participants Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo n=29 Participants Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib n=37 Participants Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score	-47.33 Percent change Standard Error 9.77	-53.57 Percent change Standard Error 8.25	-43.33 Percent change Standard Error 6.99	-47.21 Percent change Standard Error 6.26

SECONDARY outcome

Timeframe: Week 16

Population: ITT population included all randomized participants analyzed according to the intervention group allocated by randomization regardless of whether the intervention was received or not.

Outcome measures

Outcome measures
Measure	BID Cohort: Placebo n=18 Participants Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib n=27 Participants Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo n=31 Participants Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib n=48 Participants Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Percentage of Participants With Investigator's Global Assessment (IGA) of 0 or 1 At Week 16	22.2 Percentage of participants	7.4 Percentage of participants	12.9 Percentage of participants	14.6 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 16

Population: ITT population included all randomized participants analyzed according to intervention group allocated by randomization regardless of whether intervention was received or not.

The EASI index is a validated investigator-administered scoring system used to measure the severity of clinical signs in AD. Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) were each assessed for severity by the investigator or designee on a scale of "0" (absent) through "3" (severe). In addition, the area of AD involvement were assessed as a percentage by body area of head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6. 0: 0% of BSA involvement with AD; 1: 1-9%; 2: 10-29%; 2: 30-49%; 4: 50-69%; 5: 70-89% and 6: 90-100% of BSA involvement with AD. Total score ranged from 0 (minimum) to 72 (maximum); higher scores indicated greater severity of AD. Participants who achieved EASI-75 were defined as participants with reduction of EASI score by ≥75% from baseline.

Outcome measures

Outcome measures
Measure	BID Cohort: Placebo n=18 Participants Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib n=27 Participants Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo n=31 Participants Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib n=48 Participants Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Percentage of Participants Achieving EASI-75 (Reduction of EASI Score By ≥75% From Baseline) At Week 16	27.8 Percentage of participants	29.6 Percentage of participants	29.0 Percentage of participants	18.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 16

Population: ITT population included all randomized participants analyzed according to the intervention group allocated by randomization regardless of whether the intervention was received or not.

The PP-NRS is a simple assessment tool that participants used to report the intensity of their pruritus (itch) during a daily recall period. Participants were asked to rate their worst itch on a 0 (no itch) to 10 (worst itch imaginable) NRS by answering the following question: For itch intensity, "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?". The total score on the scale ranged from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicated worse symptoms. A minimum of 4 daily scores out of the 7 days is required to calculate the baseline average score.

Outcome measures

Outcome measures
Measure	BID Cohort: Placebo n=18 Participants Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib n=27 Participants Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo n=31 Participants Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib n=48 Participants Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Percentage Of Participants With Reduction of Weekly Average of Daily Peak Pruritus Numerical Rating Scale (PP-NRS) of ≥4 Points From Baseline at Week 16	11.1 Percentage of participants	18.5 Percentage of participants	12.9 Percentage of participants	20.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 16

Population: ITT population included all randomized participants analyzed according to the intervention group allocated by randomization regardless of whether the intervention was received or not.

Outcome measures

Outcome measures
Measure	BID Cohort: Placebo n=18 Participants Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib n=27 Participants Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo n=31 Participants Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib n=48 Participants Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Number of Participants With Weekly Average of Daily PP-NRS Reduction ≥4 From Baseline During The 16-Week Treatment Period	2 Participants	7 Participants	4 Participants	13 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 16

Population: ITT population included all randomized participants analyzed according to intervention group allocated by randomization regardless of whether intervention was received or not. Only those participants with data collected at specified timepoints are reported.

The EASI index is a validated investigator-administered scoring system used to measure the severity of clinical signs in AD. Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) were each assessed for severity by the investigator or designee on a scale of "0" (absent) through "3" (severe). In addition, the area of AD involvement were assessed as a percentage by body area of head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6. 0: 0% of BSA involvement with AD; 1: 1-9%; 2: 10-29%; 2: 30-49%; 4: 50-69%; 5: 70-89% and 6: 90-100% of BSA involvement with AD. Total score ranged from 0 (minimum) to 72 (maximum); higher scores indicated greater severity of AD. Baseline was defined as the Day 1 assessment value.

Outcome measures

Outcome measures
Measure	BID Cohort: Placebo n=18 Participants Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib n=24 Participants Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo n=29 Participants Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib n=37 Participants Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Absolute Change From Baseline to Week 16 In EASI Score	-12.83 Scores on a scale Standard Error 2.31	-14.00 Scores on a scale Standard Error 1.94	-10.37 Scores on a scale Standard Error 2.48	-11.34 Scores on a scale Standard Error 2.20

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 16

Population: ITT population included all randomized participants analyzed according to intervention group allocated by randomization regardless of whether intervention was received or not.

The EASI index is a validated investigator-administered scoring system used to measure the severity of clinical signs in AD. Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) were each assessed for severity by the investigator or designee on a scale of "0" (absent) through "3" (severe). In addition, the area of AD involvement were assessed as a percentage by body area of head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6. 0: 0% of BSA involvement with AD; 1: 1-9%; 2: 10-29%; 2: 30-49%; 4: 50-69%; 5: 70-89% and 6: 90-100% of BSA involvement with AD. Total score ranged from 0 (minimum) to 72 (maximum); higher scores indicated greater severity of AD. Participants who achieved EASI-50/90 were defined as participants with reduction of EASI score by ≥50% or ≥90% from baseline respectively.

Outcome measures

Outcome measures
Measure	BID Cohort: Placebo n=18 Participants Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib n=27 Participants Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo n=31 Participants Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib n=48 Participants Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Percentage of Participants Achieving EASI-50/90 (Reduction of EASI Score by ≥50% or ≥90% From Baseline) at Week 16 EASI-50	55.6 Percentage of participants	44.4 Percentage of participants	38.7 Percentage of participants	29.2 Percentage of participants
Percentage of Participants Achieving EASI-50/90 (Reduction of EASI Score by ≥50% or ≥90% From Baseline) at Week 16 EASI-90	16.7 Percentage of participants	11.1 Percentage of participants	12.9 Percentage of participants	8.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 16

Population: ITT population included all randomized participants analyzed according to the intervention group allocated by randomization regardless of whether the intervention was received or not. Only those participants with data collected at specified timepoints are reported.

BSA affected by AD were assessed for each section of the body (the possible highest score for each region was: head and neck \[10%\], trunk including genitalia \[30%\], upper limbs \[20%\], lower limbs \[40%\]) and were reported as a percentage of all major body sections combined. Total score ranges from 0% to 100%. The higher score indicates a worse value and a lower score indicates a better value. Baseline was defined as the Day 1 assessment value.

Outcome measures

Outcome measures
Measure	BID Cohort: Placebo n=14 Participants Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib n=20 Participants Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo n=29 Participants Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib n=37 Participants Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Change From Baseline to Week 16 in Percent BSA of AD	-10.45 Percent of body surface area Standard Error 4.37	-15.30 Percent of body surface area Standard Error 3.61	-7.35 Percent of body surface area Standard Error 3.38	-11.80 Percent of body surface area Standard Error 3.08

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 16

Outcome measures

Outcome measures
Measure	BID Cohort: Placebo n=16 Participants Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib n=23 Participants Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo n=26 Participants Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib n=36 Participants Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Absolute Change From Baseline to Week 16 in Weekly Average of Daily PP-NRS	-1.60 Scores on a scale Standard Error 0.66	-3.11 Scores on a scale Standard Error 0.52	-0.83 Scores on a scale Standard Error 0.51	-2.07 Scores on a scale Standard Error 0.43

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 16

Outcome measures

Outcome measures
Measure	BID Cohort: Placebo n=16 Participants Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib n=23 Participants Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo n=26 Participants Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib n=36 Participants Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Percent Change From Baseline to Week 16 in Weekly Average of Daily PP-NRS	-21.55 Percent change Standard Error 8.37	-43.53 Percent change Standard Error 6.80	-10.36 Percent change Standard Error 7.19	-30.13 Percent change Standard Error 6.08

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 16

Population: ITT population included all randomized participants analyzed according to the intervention group allocated by randomization regardless of whether the intervention was received or not.

IGA is a static 5-point measure of disease severity based on an overall assessment of the skin lesions on a 5-point scale (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease). Higher score indicated higher severity. Participants who achieved IGA\*BSA-50-75-90 were defined as participants with reduction of IGA\*BSA by ≥50% or 75% or 90% from baseline.

Outcome measures

Outcome measures
Measure	BID Cohort: Placebo n=18 Participants Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib n=27 Participants Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo n=31 Participants Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib n=48 Participants Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Percentage of Participants Achieving IGABSA-50/75/90 (Reduction of IGABSA by ≥50% or 75% or 90% From Baseline) At Week 16 IGA*BSA-90	5.6 Percentage of participants	18.5 Percentage of participants	9.7 Percentage of participants	10.4 Percentage of participants
Percentage of Participants Achieving IGABSA-50/75/90 (Reduction of IGABSA by ≥50% or 75% or 90% From Baseline) At Week 16 IGA*BSA-50	38.9 Percentage of participants	40.7 Percentage of participants	38.7 Percentage of participants	29.2 Percentage of participants
Percentage of Participants Achieving IGABSA-50/75/90 (Reduction of IGABSA by ≥50% or 75% or 90% From Baseline) At Week 16 IGA*BSA-75	22.2 Percentage of participants	25.9 Percentage of participants	22.6 Percentage of participants	18.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to 16 weeks

Population: Safety population included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the intervention they actually received.

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs that developed, worsened or became serious during the treatment-emergent period. SAE was any AE that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the investigator to the Sponsor was required.

Outcome measures

Outcome measures
Measure	BID Cohort: Placebo n=18 Participants Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib n=27 Participants Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo n=31 Participants Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib n=48 Participants Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs) and Study Intervention Discontinuation TEAEs	10 Participants	15 Participants	19 Participants	38 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs) and Study Intervention Discontinuation TESAEs	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs) and Study Intervention Discontinuation AESI	3 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs) and Study Intervention Discontinuation TEAEs leading to studyintervention discontinuation	0 Participants	2 Participants	2 Participants	9 Participants

Adverse Events

BID Cohort: Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

BID Cohort: Rilzabrutinib 400 mg BID

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

TID Cohort: Placebo

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

TID Cohort: Rilzabrutinib 400 mg TID

Serious events: 1 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	BID Cohort: Placebo n=18 participants at risk Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	BID Cohort: Rilzabrutinib 400 mg BID n=27 participants at risk Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).	TID Cohort: Placebo n=31 participants at risk Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).	TID Cohort: Rilzabrutinib 400 mg TID n=48 participants at risk Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Infections and infestations Abscess Limb	0.00% 0/18 • TEAEs were collected from Baseline (Day 1) to 16 weeks. All-cause mortality (Deaths) was collected throughout the study, approximately 97 weeks. Analysis was performed on safety population.	0.00% 0/27 • TEAEs were collected from Baseline (Day 1) to 16 weeks. All-cause mortality (Deaths) was collected throughout the study, approximately 97 weeks. Analysis was performed on safety population.	3.2% 1/31 • Number of events 1 • TEAEs were collected from Baseline (Day 1) to 16 weeks. All-cause mortality (Deaths) was collected throughout the study, approximately 97 weeks. Analysis was performed on safety population.	0.00% 0/48 • TEAEs were collected from Baseline (Day 1) to 16 weeks. All-cause mortality (Deaths) was collected throughout the study, approximately 97 weeks. Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cutaneous T-Cell Lymphoma	0.00% 0/18 • TEAEs were collected from Baseline (Day 1) to 16 weeks. All-cause mortality (Deaths) was collected throughout the study, approximately 97 weeks. Analysis was performed on safety population.	0.00% 0/27 • TEAEs were collected from Baseline (Day 1) to 16 weeks. All-cause mortality (Deaths) was collected throughout the study, approximately 97 weeks. Analysis was performed on safety population.	0.00% 0/31 • TEAEs were collected from Baseline (Day 1) to 16 weeks. All-cause mortality (Deaths) was collected throughout the study, approximately 97 weeks. Analysis was performed on safety population.	2.1% 1/48 • Number of events 1 • TEAEs were collected from Baseline (Day 1) to 16 weeks. All-cause mortality (Deaths) was collected throughout the study, approximately 97 weeks. Analysis was performed on safety population.

Other adverse events

Additional Information

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