A Phase 2, randomized, double-blind, placebo-controlled, multicenter proof-of-concept study evaluating efficacy and safety of rilzabrutinib (SAR444671) in adult patients with moderate-to-severe atopic dermatitis who are inadequate responders or intolerant to topical corticosteroids

- Atopic Dermatitis (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 * 16 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.

- 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-*, JAK inhibitors, dupilumab, and any other
biologic or targeted-synthetic disease modifier drug not mentioned in this
exclusion criterion or in exclusion criterion above, 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 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.
- Has 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