Clinical trial NCT05018806: Proof of Concept Study of Rilzabrutinib in Adult Patients With Moderate-to-severe Atopic Dermatitis
Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Proof-of-concept Study Evaluating Efficacy and Safety of Rilzabrutinib in Adult Patients With Moderate-to-severe Atopic Dermatitis Who Are Inadequate Responders or Intolerant to Topical Corticosteroids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atopic Dermatitis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-08-24
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score
timeFrame: Baseline (Day 1) to Week 16
Secondary outcomes:
measure: Percentage of Participants With Investigator's Global Assessment (IGA) of 0 or 1 At Week 16
timeFrame: Week 16
measure: Percentage of Participants Achieving EASI-75 (Reduction of EASI Score By ≥75% From Baseline) At Week 16
timeFrame: Baseline (Day 1) and at Week 16
measure: 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
timeFrame: Baseline (Day 1) and at Week 16
measure: Number of Participants With Weekly Average of Daily PP-NRS Reduction ≥4 From Baseline During The 16-Week Treatment Period
timeFrame: Baseline (Day 1) and Week 16
measure: Absolute Change From Baseline to Week 16 In EASI Score
timeFrame: Baseline (Day 1) to Week 16
measure: Percentage of Participants Achieving EASI-50/90 (Reduction of EASI Score by ≥50% or ≥90% From Baseline) at Week 16
timeFrame: Baseline (Day 1) and at Week 16
measure: Change From Baseline to Week 16 in Percent BSA of AD
timeFrame: Baseline (Day 1) to Week 16
measure: Absolute Change From Baseline to Week 16 in Weekly Average of Daily PP-NRS
timeFrame: Baseline (Day 1) to Week 16
measure: Percent Change From Baseline to Week 16 in Weekly Average of Daily PP-NRS
timeFrame: Baseline (Day 1) to Week 16
measure: Percentage of Participants Achieving IGA*BSA-50/75/90 (Reduction of IGA*BSA by ≥50% or 75% or 90% From Baseline) At Week 16
timeFrame: Baseline (Day 1) and at Week 16
measure: 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
timeFrame: Baseline (Day 1) to 16 weeks
Other outcomes:
Locations:
city: Northridge
country: United States
facility: Antelope Valley Clinical Trials Site Number : 8400001
state: California
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates, PC Site Number : 8400008
state: Colorado
city: Miami
country: United States
facility: Florida International Research Center Site Number : 8400002
state: Florida
city: Louisville
country: United States
facility: Skin Sciences, PLLC Site Number : 8400005
state: Kentucky
city: Louisville
country: United States
facility: DS Research of Kentucky, LLC Site Number : 8400004
state: Kentucky
city: Ridgeland
country: United States
facility: Integrative Skin Care of MS/SKYCRNG Site Number : 8400011
state: Mississippi
city: North Charleston
country: United States
facility: National Allergy and Asthma Research, LLC. Site Number : 8400007
state: South Carolina
city: Austin
country: United States
facility: Orion Clinical Research Site Number : 8400003
state: Texas
city: El Paso
country: United States
facility: E.P.I.M.R.D dba Western Sky Research, Inc. Site Number : 8400009
state: Texas
city: Red Deer
country: Canada
facility: Investigational Site Number : 1240008
state: Alberta
city: London
country: Canada
facility: Investigational Site Number : 1240001
state: Ontario
city: Markham
country: Canada
facility: Investigational Site Number : 1240002
state: Ontario
city: Sudbury
country: Canada
facility: Investigational Site Number : 1240013
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1240011
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1240007
state: Ontario
city: Quebec
country: Canada
facility: Investigational Site Number : 1240004
city: Santiago
country: Chile
facility: Investigational Site Number : 1520004
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520002
state: Reg Metropolitana De Santiago
city: Olomouc
country: Czechia
facility: Investigational Site Number : 2030004
city: Pardubice
country: Czechia
facility: Investigational Site Number : 2030003
city: Plzen
country: Czechia
facility: Investigational Site Number : 2030002
city: Praha 6
country: Czechia
facility: Investigational Site Number : 2030001
city: Bad Bentheim
country: Germany
facility: Investigational Site Number : 2760001
city: Friedrichshafen
country: Germany
facility: Investigational Site Number : 2760002
city: Utrecht
country: Netherlands
facility: Investigational Site Number : 5280001
city: Lodz
country: Poland
facility: Investigational Site Number : 6160001
state: Lódzkie
city: Gdansk
country: Poland
facility: Investigational Site Number : 6160005
state: Pomorskie
city: Chojnice
country: Poland
facility: Investigational Site Number : 6160008
city: Lodz
country: Poland
facility: Investigational Site Number : 6160002
city: Warszawa
country: Poland
facility: Investigational Site Number : 6160004
Study officials:
References: