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

NCT05018806 | Completed Phase 2 FDA Drug

• 3 other identifiers: ACT17207U1111-1261-75652021-001704-15
• Study Type: interventional
• Target: 124
• Locations: 7 countries
• Sites: 31

Brief Summary

This was a parallel treatment, Phase 2, double-blind, 2-arm, placebo-controlled study with 2 staggered cohorts (2 arms in each cohort) to evaluate the efficacy and safety of rilzabrutinib in adult participants (aged at least 18 years) with moderate-to-severe AD and intolerance or inadequate response to topical corticosteroids (TCS). The total study duration per participant was expected to be approximately 21 weeks, including up to 4 weeks of screening, 16 weeks of on-treatment double-blind period, 1 week of post-treatment follow-up.

Conditions

Atopic Dermatitis

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score

  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.

  Baseline (Day 1) to Week 16

Secondary Outcomes (11)

• Percentage of Participants With Investigator's Global Assessment (IGA) of 0 or 1 At Week 16

  Week 16

• Percentage of Participants Achieving EASI-75 (Reduction of EASI Score By ≥75% From Baseline) At Week 16

  Baseline (Day 1) and at Week 16

• 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

  Baseline (Day 1) and at Week 16

• Number of Participants With Weekly Average of Daily PP-NRS Reduction ≥4 From Baseline During The 16-Week Treatment Period

  Baseline (Day 1) and Week 16

• Absolute Change From Baseline to Week 16 In EASI Score

  Baseline (Day 1) to Week 16

Study Arms (4)

BID cohort: Placebo

PLACEBO COMPARATOR

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).

Drug: Placebo

BID cohort: Rilzabrutinib

EXPERIMENTAL

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).

Drug: Rilzabrutinib

TID cohort: Placebo

PLACEBO COMPARATOR

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).

Drug: Placebo

TID cohort: Rilzabrutinib

EXPERIMENTAL

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).

Drug: Rilzabrutinib

Interventions

Placebo DRUG

Pharmaceutical form: Tablet Route of administration: Oral

BID cohort: Placebo; TID cohort: Placebo

Rilzabrutinib DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Also known as: PRN1008/SAR444671

BID cohort: Rilzabrutinib; TID cohort: Rilzabrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• AD as defined by the American Academy of Dermatology Consensus Criteria.
• History of AD for at least 12 months prior to baseline as determined by the Investigator through patient interview.
• Eczema Area and Severity Index (EASI) score ≥ 12 at screening and at baseline.
• IGA score ≥ 3 (on the 0 to 4 IGA scale) at baseline.
• BSA of AD involvement ≥ 10% at baseline.
• Documented inadequate response or intolerance to TCS within 6 months prior to baseline visit
• Baseline PP-NRS score for maximum itch intensity ≥4.
• All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• For optional substudy only: Willingness to have 2 tape strips for comparison of baseline and treatment response.

You may not qualify if:

• Skin comorbidities that may interfere with study assessments such as psoriasis, tinea corporis, lupus erythematosus.
• Conditions that may predispose the patient to excessive bleeding.
• Any other clinically significant disease, condition, or medical history that, in the opinion of the Investigator, would interfere with participant safety, trial evaluations, and/or trial procedures.
• Laboratory abnormalities at the screening visit
• History of serious infections requiring intravenous therapy with the potential for recurrence (as judged by the Site Investigator and the Sponsor Medical Monitor), with less than 4 weeks interval between resolution of serious infection and first dose of study drug, or currently active moderate to severe infection at Screening (Grade 2 or higher) including active coronavirus disease 2019 (COVID-19).
• Live vaccine except Bacille Calmette Guerin-vaccination within 28 days prior to Day 1 or plan to receive one during the trial; Bacille Calmette Guerin-vaccination within 12 months prior to Screening.
• COVID-19 vaccine within 14 days prior to Study Day 1.
• Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate rilzabrutinib/placebo absorption.
• Initiation of prescription moisturizers (with or without additives such as ceramide, hyaluronic acid, urea, or filaggrin), topical anesthetics or antihistamines during the screening period.
• Use of TCS, topical calcineurin (tacrolimus, and/or pimecrolimus) or topical phosphodiesterase 4 inhibitor within 1 week prior to baseline and as concomitant medication.
• Use of systemic corticosteroids within 4 weeks prior to baseline and as concomitant medication.
• Phototherapy for AD or regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks prior to baseline or likely to be required as concomitant procedure during the study.
• Use of anti-CD20 drugs such as rituximab, ofatumumab, other long-acting biologics within 6 months prior to baseline (or shorter if there is documented B cell reconstitution for anti-CD20 drugs).
• Use of proton pump inhibitor drugs such as omeprazole and esomeprazole within 3 days of baseline (it is acceptable to change participant to H2 receptor blocking drugs prior to baseline).
• Concomitant use of known systemic strong-to-moderate inhibitors and inducers of cytochrome P450 3A (CYP3A) within 14 days or 5 half-lives (whichever is longer) prior to baseline.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (31)

Antelope Valley Clinical Trials Site Number : 8400001

Northridge, California, 91325, United States

Location

Asthma and Allergy Associates, PC Site Number : 8400008

Colorado Springs, Colorado, 80907, United States

Location

Florida International Research Center Site Number : 8400002

Miami, Florida, 33173, United States

Location

Skin Sciences, PLLC Site Number : 8400005

Louisville, Kentucky, 40217, United States

Location

DS Research of Kentucky, LLC Site Number : 8400004

Louisville, Kentucky, 40241, United States

Location

Integrative Skin Care of MS/SKYCRNG Site Number : 8400011

Ridgeland, Mississippi, 39157, United States

Location

National Allergy and Asthma Research, LLC. Site Number : 8400007

North Charleston, South Carolina, 29420, United States

Location

Orion Clinical Research Site Number : 8400003

Austin, Texas, 78759, United States

Location

E.P.I.M.R.D dba Western Sky Research, Inc. Site Number : 8400009

El Paso, Texas, 79903, United States

Location

Investigational Site Number : 1240008

Red Deer, Alberta, T4P 1K4, Canada

Location

Investigational Site Number : 1240013

Greater Sudbury, Ontario, P3E 5M4, Canada

Location

Investigational Site Number : 1240001

London, Ontario, N6A2C2, Canada

Location

Investigational Site Number : 1240002

Markham, Ontario, L3P 1X3, Canada

Location

Investigational Site Number : 1240011

Toronto, Ontario, M2N 3A6, Canada

Location

Investigational Site Number : 1240007

Toronto, Ontario, M3H 5Y8, Canada

Location

Investigational Site Number : 1240004

Québec, G1V 4T3, Canada

Location

Investigational Site Number : 1520004

Santiago, Reg Metropolitana de Santiago, 7580206, Chile

Location

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, 7640881, Chile

Location

Investigational Site Number : 1520002

Santiago, Reg Metropolitana de Santiago, 8420383, Chile

Location

Investigational Site Number : 2030004

Olomouc, 779 00, Czechia

Location

Investigational Site Number : 2030003

Pardubice, 53002, Czechia

Location

Investigational Site Number : 2030002

Pilsen, 30599, Czechia

Location

Investigational Site Number : 2030001

Prague, 160 00, Czechia

Location

Investigational Site Number : 2760001

Bad Bentheim, 48455, Germany

Location

Investigational Site Number : 2760002

Friedrichshafen, 88045, Germany

Location

Investigational Site Number : 5280001

Utrecht, 3584 CX, Netherlands

Location

Investigational Site Number : 6160001

Lodz, Lódzkie, 90-436, Poland

Location

Investigational Site Number : 6160005

Gdansk, Pomeranian Voivodeship, 80-546, Poland

Location

Investigational Site Number : 6160008

Chojnice, 89600, Poland

Location

Investigational Site Number : 6160002

Lodz, 93-530, Poland

Location

Investigational Site Number : 6160004

Warsaw, 00-215, Poland

Location

Related Links

• ACT17207 Moderate-to-severe Atopic Dermatitis website

MeSH Terms

Conditions

Dermatitis, Atopic

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2021
• First Posted: August 24, 2021
• Study Start: September 9, 2021
• Primary Completion: June 23, 2023
• Study Completion: June 23, 2023
• Last Updated: June 21, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share

Locations

NL (1); PL (5); CL (3); DE (2); US (9); CA (7); CZ (4)