E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• Assess the efficacy of rilzabrutinib in participants with atopic dermatitis (AD) |
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E.2.2 | Secondary objectives of the trial |
• Assess the efficacy of rilzabrutinib at different time points • Assess the safety of rilzabrutinib |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
To evaluate efficacy, safety, tolerability and PK in Japanese AD participants |
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E.3 | Principal 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.
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E.4 | Principal 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. - 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change in Eczema Area and Severity Index (EASI) score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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. Proportion of participants achieving IGA*BSA-50/75/90 (reduction of IGA*BSA by ≥ 50% or 75% or 90% from baseline) at Week 16 10. Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) 11. Incidence of study investigational medicinal product (IMP) discontinuation and withdrawals due to TEAEs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 2, 6, 9. At week 16 3, 5, 7, 8. and 11. From baseline to Week 16 4. Until Week 16 10. Up to week 17
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Chile |
United States |
Poland |
Bulgaria |
Netherlands |
Czechia |
Germany |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 20 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 20 |