E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
SLE Sub-protocol: Systemic Lupus Erythematosus pSS Sub-protocol: Primary Sjögren’s Syndrome RA Sub-protocol: Rheumatoid Arthritis |
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E.1.1.1 | Medical condition in easily understood language |
Lupus, Sjögren’s Syndrome and Arthritis are autoimmune diseases that develops when body's immune system overreacts to unknown stimulus making antibodies/proteins directed against own's body tissues. |
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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 | PT |
E.1.2 | Classification code | 10042945 |
E.1.2 | Term | Systemic lupus erythematosus |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040767 |
E.1.2 | Term | Sjogren's syndrome |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 |
SLE Sub-protocol: -To compare the efficacy of branebrutinib with PBO at Week 24 in the treatment of subjects with SLE
pSS Sub-protocol: -To compare the efficacy of branebrutinib with PBO at Week 24 in the treatment of subjects with pSS
RA Sub-protocol: -To compare the efficacy of branebrutinib with PBO at Week 12 in the treatment of subjects with moderate to severe RA on a stable background of MTX who have had an inadequate response to MTX |
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E.2.2 | Secondary objectives of the trial |
SLE Sub-protocol: -To compare the efficacy of branebrutinib with PBO at Week 24 in the treatment of subjects with SLE. -To compare the efficacy of branebrutinib with PBO on measures of global and organ-specific clinical responses at Week 24 in the treatment of subjects with SLE. - To compare the safety and tolerability of branebrutinib with PBO in subjects with SLE.
pSS Sub-protocol: -To compare the safety and tolerability of branebrutinib with PBO in subjects with pSS.
RA Sub-protocol: -To compare the efficacy of branebrutinib with PBO at Week 12 in the treatment of subjects with moderate to severe RA on a stable background of MTX who have had an inadequate response to MTX. - To evaluate the safety and tolerability at Week 24 of switching at Week 12 from branebrutinib or PBO to abatacept in subjects with RA.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Sub-Protocol for Systemic Lupus Erythematosus (SLE): - Active SLE as defined by the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) classification. - Diagnosed with SLE more than 24 weeks before screening visit.
Sub-Protocol for primary Sjögren's Syndrome (pSS): - Moderate to severe pSS, meeting ACR-EULAR classification criteria.
Sub-Protocol for active Rheumatoid Arthritis (RA): - Moderate to severe adult-onset RA. - ACR global functional status class I to III.
For all sub-studies: - Women and men must agree to follow instructions for methods of contraception.
Please, be referred to the Protocol document for a complete list of Inclusion citeria. |
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E.4 | Principal exclusion criteria |
Sub-Protocol for Systemic Lupus Erythematosus (SLE): - Certain other autoimmune diseases and overlap syndromes.
Sub-Protocol for primary Sjögren's Syndrome (pSS): - Certain other immune-mediated diseases, active fibromyalgia, or other medical conditions.
Sub-Protocol for Rheumatoid Arthritis (RA): - Diagnosis with juvenile arthritis or idiopathic arthritis before age 16.
For all sub-studies: - History of any significant drug allergy - Active infection, significant concurrent medical condition, or clinically significant abnormalities
Please, be referred to the Protocol document for a complete list of Exclusion citeria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. SLE: mCLASI activity score response [ Time Frame: at 24 weeks ] Proportion of participants with a ≥ 50% reduction of mCLASI from baseline
2. pSS: Proportion of subjects with changes in a composite score that includes ESSPRI (EULAR Sjögren's Syndrome Patient Reported Index), ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index), ocular staining, salivary flow and serological marker [ Time Frame: at 24 weeks ] Clinically significant improvements from baseline in ESSPRI, ESSDAI, ocular staining, salivary flow, and serological marker (rheumatoid factor [RF], IgG, complement C3 or C4, cryoglobulin) used in the composite measure.
3. RA: ACR50 response [ Time Frame: at 12 weeks ] Proportion of participants achieving ACR50 response (American College of Rheumatology 50 criteria) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
SLE Sub-Protocol: -Week 20 and Week 24 pSS Sub-Protocol: - Week 24 RA Sub-protocol: -Week 12 |
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E.5.2 | Secondary end point(s) |
1. SLE: SLEDAI-2K score response [ Time Frame: at 24 weeks ] Change from baseline in SLEDAI-2K score (Systemic Lupus Erythematosus Disease Activity Index 2000)
2. SLE: BILAG-based Composite Lupus Assessment response [ Time Frame: at 24 weeks ] Change from baseline in BILAG-based (British Isles Lupus Assessment Group) Composite Lupus Assessment response
3. RA: DAS28-CRP response [ Time Frame: at 12 weeks ] Change from baseline in DAS28-CRP (Disease Activity Score 28 - C reactive protein)
4. RA: DAS28-ESR response [ Time Frame: at 12 weeks ] Change from baseline in DAS28-ESR (Disease Activity Score 28 - Erythrocyte Sedimentation Rate)
5. RA: SDAI response [ Time Frame: at 12 weeks ] Change from baseline in SDAI (Simplified Disease Activity Index)
6. RA: CDAI response [ Time Frame: at 12 weeks ] Change from baseline in CDAI (Clinical Disease Activity Index)
7. RA: ACR20 response [ Time Frame: at 12 weeks ] Proportion of participants achieving ACR20 response (American College of Rheumatology 20 criteria)
8. RA: ACR70 response [ Time Frame: at 12 weeks ] Proportion of participants achieving ACR70 response (American College of Rheumatology 70 criteria)
9. SLE, pSS, RA: Safety [ Time Frame: up to 28 weeks ] Incidence of Serious Adverse Events, Adverse Events; number of clinically significant changes in lab assessment of blood, number of clinically significant changes in vital sign of body temperature, blood pressure, and respiratory rate; number of clinically significant changes in electrocardiogram. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
SLE Sub-protocol: -Week 24 -Week 28 (safety)
pSS Sub-protocol: -Week 24 -Week 28 (safety)
RA Sub-protocol: -Week 12 -Week 28 (safety) |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | 7 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 |
Argentina |
Mexico |
United States |
France |
Poland |
Netherlands |
Spain |
Germany |
Belgium |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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SLE Sub-protocol/pSS Sub-protocol/RA Sub-protocol: -Final date on which data for the primary endpoint was or is expected to be collected, if it is not the same.
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |