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

NCT ID: NCT05018806

Last Updated: 2024-06-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-09
• Study Completion Date: 2023-06-23

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pharmaceutical form: Tablet Route of administration: Oral

BID cohort: Rilzabrutinib

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).

Group Type: EXPERIMENTAL

Rilzabrutinib

Intervention Type: DRUG

Pharmaceutical form: Tablet Route of administration: Oral

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pharmaceutical form: Tablet Route of administration: Oral

TID cohort: Rilzabrutinib

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).

Group Type: EXPERIMENTAL

Rilzabrutinib

Intervention Type: DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Interventions

Placebo

Pharmaceutical form: Tablet Route of administration: Oral

Intervention Type: DRUG

Rilzabrutinib

Pharmaceutical form: Tablet Route of administration: Oral

Intervention Type: DRUG

Other Intervention Names

PRN1008/SAR444671

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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 mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, dapsone, intravenous immunoglobulin (IVIG), Kineret (anakinra), Enbrel (etanercept), or any other immunosuppressant not mentioned in this exclusion criterion within 4 weeks prior to baseline.
• Use of infliximab, adalimumab, golimumab, abatacept, tocilizumab, certolizumab, secukinumab, IFN-γ, JAK inhibitors, dupilumab, and any other biologic or targeted-synthetic disease modifier drug not mentioned in this exclusion criterion or in exclusion criterion, as well as plasmapheresis within 12 weeks prior to baseline.
• 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.
• Previous use of a BTK inhibitor.
• Had received any investigational drug (or is currently using an investigational device) within the 30 days before baseline, or at least 5 times the respective elimination half-life time (whichever is longer).
• Active TB or a history of incompletely treated TB, Quantiferon positive patients, Clinically significant abnormality consistent with prior/active TB infection based upon chest radiograph with at least posterior-anterior view, Suspected extrapulmonary TB infection, or patients at high risk of contracting TB.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Antelope Valley Clinical Trials Site Number : 8400001

Northridge, California, United States

Asthma and Allergy Associates, PC Site Number : 8400008

Colorado Springs, Colorado, United States

Florida International Research Center Site Number : 8400002

Miami, Florida, United States

Skin Sciences, PLLC Site Number : 8400005

Louisville, Kentucky, United States

DS Research of Kentucky, LLC Site Number : 8400004

Louisville, Kentucky, United States

Integrative Skin Care of MS/SKYCRNG Site Number : 8400011

Ridgeland, Mississippi, United States

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

North Charleston, South Carolina, United States

Orion Clinical Research Site Number : 8400003

Austin, Texas, United States

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

El Paso, Texas, United States

Investigational Site Number : 1240008

Red Deer, Alberta, Canada

Investigational Site Number : 1240013

Greater Sudbury, Ontario, Canada

Investigational Site Number : 1240001

London, Ontario, Canada

Investigational Site Number : 1240002

Markham, Ontario, Canada

Investigational Site Number : 1240011

Toronto, Ontario, Canada

Investigational Site Number : 1240007

Toronto, Ontario, Canada

Investigational Site Number : 1240004

Québec, , Canada

Investigational Site Number : 1520004

Santiago, Reg Metropolitana de Santiago, Chile

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, Chile

Investigational Site Number : 1520002

Santiago, Reg Metropolitana de Santiago, Chile

Investigational Site Number : 2030004

Olomouc, , Czechia

Investigational Site Number : 2030003

Pardubice, , Czechia

Investigational Site Number : 2030002

Pilsen, , Czechia

Investigational Site Number : 2030001

Prague, , Czechia

Investigational Site Number : 2760001

Bad Bentheim, , Germany

Investigational Site Number : 2760002

Friedrichshafen, , Germany

Investigational Site Number : 5280001

Utrecht, , Netherlands

Investigational Site Number : 6160001

Lodz, Lódzkie, Poland

Investigational Site Number : 6160005

Gdansk, Pomeranian Voivodeship, Poland

Investigational Site Number : 6160008

Chojnice, , Poland

Investigational Site Number : 6160002

Lodz, , Poland

Investigational Site Number : 6160004

Warsaw, , Poland

Countries

United States; Canada; Chile; Czechia; Germany; Netherlands; Poland

Related Links

https://www.sanofistudies.com/eczema

ACT17207 Moderate-to-severe Atopic Dermatitis website

Other Identifiers

U1111-1261-7565

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACT17207

Identifier Type: OTHER

Identifier Source: secondary_id

2021-001704-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ACT17207

Identifier Type: -

Identifier Source: org_study_id