Atopic dermatitis MedDRA version: 21.1 Level: LLT Classification code 10003639 Term: Atopic dermatitis System Organ Class: 100000004858
Conditions
Interventions
Product Name: Rilzabrutinib
Product Code: SAR444671
Pharmaceutical Form: Tablet
INN or Proposed INN: Rilzabrutinib
Current Sponsor code: SAR444671
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Sanofi aventis recherche et developpement
Eligibility
Sex/Gender
All
Inclusion 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 = 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
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-?, 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 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 r
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Assess the efficacy of rilzabrutinib in participants with atopic dermatitis (AD);Secondary Objective: •Assess the efficacy of rilzabrutinib at different time points •Assess the safety of rilzabrutinib;Primary end point(s): Percent change in Eczema Area and Severity Index (EASI) score;Timepoint(s) of evaluation of this end point: From baseline to Week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportion of participants with Investigator's Global Assessment (IGA) of 0 or 1 (disease free or almost disease free) compared to placebo 2. Proportion of participants achieving EASI-75 - Defined as reduction of EASI score by =75% from baseline 3. Proportion of participants with reduction of weekly average of daily peak pruritus Numerical Rating Scale (PP-NRS) of =4 points 4. Time to onset of effect on pruritus - Defined as =4 points reduction of weekly average of daily PP-NRS from baseline during the 16-week treatment period 5. Absolute change in EASI score 6. Proportion of participants achieving EASI-50/90 7. Change in percent body surface area (BSA) of EASI. 8. Change on weekly average of daily PP-NRS - Based on daily participant assessments documented in their electronic diary 9. Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) 10. Incidence of study investigational medicinal product (IMP) discontinuation and withdrawals due to TEAEs ;Timepoint(s) of evaluation of this end point: 1., 2. and 6. At week 16 3., 5., 7., 8. and 10. From baseline to Week 16 9. Up to week 17 4. Until Week 16 | — |
Countries
Canada, Czechia, Czech Republic, Germany, Netherlands, Poland, United States
Outcome results
None listed