Proof of Concept Study of Rilzabrutinib in Adult Patients... | NCT05018806

ID	Type	Description
U1111-1261-7565	Registry Identifier	ICTRP
ACT17207	Other Identifier	Sanofi Identifier
2021-001704-15	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Pharmaceutical form: Tablet Route of administration: Oral	BID cohort: Placebo TID cohort: Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Percentage of Participants With Investigator's Global Assessment (IGA) of 0 or 1 At Week 16	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.	Week 16

Eligibility Module

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.

ID	Term
D012873	Skin Diseases, Genetic
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D003872	Dermatitis
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D017443	Skin Diseases, Eczematous
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases