E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active Systemic Lupus Erythematosus
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E.1.1.1 | Medical condition in easily understood language |
Active Systemic Lupus Erythematosus |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of nipocalimab vs placebo in participants with active systemic lupus erythematosus (SLE) |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the safety and tolerability of nipocalimab vs placebo in participants with active SLE 2. To evaluate the pharmacokinetics (PK) and immunogenicity of nipocalimab in participants with active SLE |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male or female, 18 to 65 years of age (inclusive) at the time of consent. -Has a clinical diagnosis of SLE ≥6 months prior to the screening visit and according to Systemic Lupus International Collaborating Clinics (SLICC)-2012 classification criteria: at least 4 criteria fulfilled, with at least one clinical criterion AND one immunologic criterion. -Has at least 1 BILAG A and/or 2 BILAG B scores observed during screening. -Must have at least moderately active SLE, as defined as SLEDAI-2K score ≥6 at screening visit. Must also have SLEDAI 2K ≥4 for clinical features (ie, SLEDAI-2K score excluding headache and laboratory abnormalities) present at Week 0 prior to randomization. -Must be receiving one or more of the following protocol-permitted, systemic standard-of-care treatments: a) Oral GCs (average daily dose ≤20 mg of prednisone or equivalent) for ≥6 weeks and at a stable dose ≥4 weeks prior to first administration of study intervention. If currently not using oral GCs, must not have received them for ≥6 weeks prior to the first administration of study intervention. b) Antimalarials (≤250 mg/day [3 mg/kg/day] chloroquine, ≤400 mg/day hydroxychloroquine, and/or ≤100 mg/day quinacrine) at a stable dose for ≥12 weeks prior to first administration of study intervention. c) If using one or more of the following immunomodulatory drugs, must be on a stable dose for ≥8 weeks prior to first administration of study intervention: • Mycophenolate mofetil (MMF) ≤2 g/day • Mycophenolic acid (MPA) ≤1.5 g/day • Azathioprine (AZA)/6 mercaptopurine (6-MP) ≤2 mg/kg/day; up to 100 mg/day for participants weighing ≤50 kg • Oral methotrexate (MTX) ≤25 mg/week or SC or intramuscular (IM) MTX ≤20 mg/week with concomitant folic acid or folinic acid. No more than 2 immunomodulatory drugs listed above (MMF, MPA, AZA, 6-MP, MTX) is allowed. |
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E.4 | Principal exclusion criteria |
-Current or history of, severe, progressive, or uncontrolled renal disease, with the exception of active LN. Have severe active LN as determined by sponsor (or designee) adjudication. -Anticipated to require dialysis within 6 months. -Comorbidities (other than SLE, eg, asthma, chronic obstructive pulmonary disease) which have required 3 or more courses of systemic GCs within the previous 12 months and likely to require multiple courses of GCs within 6 months. -Has any unstable or progressive manifestation of SLE -Has other inflammatory diseases that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis (RA), psoriatic arthritis, RA/lupus overlap, psoriasis, Crohn’s disease, or active Lyme disease. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of participants achieving an SLE Responder Index (SRI)-4 composite response |
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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 baseline active mucocutaneous lupus manifestations (Cutaneous Lupus Erythematosus Disease Area and Severity Index [CLASI] activity score ≥6) achieving ≥50% reduction in the CLASI) activity score 2. Proportion of participants with baseline arthritis (with at least 4 active joints at baseline) achieving ≥50% reduction in active joints 3. Proportion of participants with ≥4 point improvement in SLE disease activity index 2000 (SLEDAI-2K) 4. Proportion of participants achieving the British Isles Lupus Assessment Group (BILAG) Composite Lupus Assessment (BICLA) response 5. Time to first flare, with flare defined as either 1 or more new BILAG A or 2 or more new BILAG B scores 6. Proportion of participants achieving SRI-4 composite response 7. Proportion of participants receiving ≥10 mg/day prednisone or equivalent at baseline who achieve Week 6 – 16 glucocorticoid (GC) taper goal (at Week 16 to ≤7.5 mg/day prednisone or equivalent) and maintain that reduction 8. Proportion of participants with treatment emergent adverse events (AEs) 9. Proportion of participants with treatment emergent serious adverse events (SAEs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Week 24 2. Week 24 3. Week 24 4. Week 24 5. Week 24 6. Week 52 7. Week 24 8. Through Week 58 9. Through Week 58 |
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity and tolerability |
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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 | 3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
Colombia |
Hong Kong |
Japan |
Russian Federation |
South Africa |
Taiwan |
Ukraine |
United States |
Bulgaria |
Germany |
Hungary |
Poland |
Spain |
Argentina |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 29 |