A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Nipocalimab in Adult Participants With Active Lupus Nephritis
Trial Snapshot
- Phase
- Phase 2
- Status
- Not yet recruiting
- Enrollment
- 80
- Primary Endpoint
- Percentage of Participants Achieving Complete Renal Response (CRR)
Study Overview
Brief Summary
The purpose of this study is to evaluate the efficacy of nipocalimab versus placebo in participants with active Lupus Nephritis (LN).
Detailed Description
LN is a heterogeneous autoimmune disease that includes a broad spectrum of clinical forms, ranging from those with lesions confined to the skin (cutaneous lupus erythematosus [CLE]) to others that involve one or more vital internal organs (systemic lupus erythematosus [SLE]). Renal involvement due to SLE is termed LN. Nipocalimab (also referred to as JNJ-80202135 or M281) is a fully human aglycosylated immunoglobulin (Ig) G1 monoclonal antibody designed to selectively bind, saturate, and block the IgG binding site on the endogenous neonatal fragment crystallizable receptor (FcRn). By targeting the IgG binding site on FcRn, nipocalimab is expected to block the binding and, hence, recycling of IgG into circulation, resulting in a decrease in circulating IgG antibody levels, including pathogenic IgG autoantibodies and alloantibodies. The study will consist of a screening period (less than or equal to [<=] 8 Week), double-blind treatment period (52 Week), and a safety follow-up period (6 Week). Safety assessment will include adverse events (AEs), serious adverse events (SAEs), laboratory parameters (hematology and chemistry) and vital signs. The total duration of the main study is up to 66 weeks.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Kidney biopsy documentation of International Society of Nephrology (ISN)/Renal Pathology Society (RPS) proliferative nephritis: Class III or IV (with or without concomitant Class V) within the last 6 months prior to screening or performed during screening
- •Urine Protein to Creatinine Ratio (UPCR) greater than or equal to (>=) 1.0 milligram/milligram (mg/mg) measured twice during screening
- •Currently receiving prednisone equivalent dose of 1 milligram/kilogram/day (mg/kg/day) or less than or equal to (<=) 60 mg/day whichever is lower, or less. Must be receiving prednisone equivalent of 10 mg/day or more at screening and randomization. Treated for >= 6 weeks with stable dosing >= 2 weeks prior to first administration of study intervention
- •If receiving angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blockers (ARB), a stable dose for at least 2 weeks prior to first administration of study intervention
- •Is recommended to be up-to-date on all age-appropriate vaccinations prior to screening per routine local medical guidelines. For study participants who received locally-approved (and including emergency use-authorized) coronavirus disease 2019 (COVID-19) vaccines recently prior to study entry, follow applicable local vaccine labelling, guidelines, and standards-of-care for patients receiving immune-targeted therapy when determining an appropriate interval between vaccination and study enrolment
Exclusion Criteria
- •Comorbidities (other than Lupus Nephritis, example, asthma, chronic obstructive pulmonary disease) which have required 3 or more courses of systemic glucocorticoids within the previous 12 months
- •Has other inflammatory diseases that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis (RA), psoriatic arthritis (PsA), RA/lupus overlap, psoriasis, Crohn's disease, or active Lyme disease
- •Has received oral cyclophosphamide within 3 months or intravenous (IV) cyclophosphamide within 6 months prior to first administration of study intervention
- •Has a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, before screening
- •COVID-19 infection: During the 6 weeks prior to baseline, have had any of the following (a) confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (test positive), or (b) suspected SARS-CoV-2 infection (clinical features of COVID-19 without documented test results), or (c) close contact with a person with known or suspected SARS-CoV-2 infection
Arms & Interventions
Group 1: Placebo
Participants will receive placebo intravenously (IV) every two weeks (q2w) from Week 0 through Week 50 along with standard-of-care treatment of mycophenolate mofetil (MMF) or mycophenolic acid (MPA) and glucocorticoid. Participants who will complete the assessments at Week 52 and have achieved complete renal response (CRR) may have the option to participate in the long-term extension (LTE) until unblinding of the study.
Intervention: Placebo (Other)
Group 1: Placebo
Participants will receive placebo intravenously (IV) every two weeks (q2w) from Week 0 through Week 50 along with standard-of-care treatment of mycophenolate mofetil (MMF) or mycophenolic acid (MPA) and glucocorticoid. Participants who will complete the assessments at Week 52 and have achieved complete renal response (CRR) may have the option to participate in the long-term extension (LTE) until unblinding of the study.
Intervention: Standard-of-care treatment (Drug)
Group 2: Nipocalimab Dose 1
Participants will receive nipocalimab dose 1 IV q2w from Week 0 through Week 50 along with standard-of-care treatment of MMF or MPA and glucocorticoid. Participants who will complete the assessments at Week 52 and have achieved CRR may have the option to participate in the LTE of the study.
Intervention: Nipocalimab (Drug)
Group 2: Nipocalimab Dose 1
Participants will receive nipocalimab dose 1 IV q2w from Week 0 through Week 50 along with standard-of-care treatment of MMF or MPA and glucocorticoid. Participants who will complete the assessments at Week 52 and have achieved CRR may have the option to participate in the LTE of the study.
Intervention: Standard-of-care treatment (Drug)
Group 3: Nipocalimab Dose 2
Participants will receive nipocalimab dose 2 IV q2w from Week 0 through Week 50 along with standard-of-care treatment of MMF or MPA and glucocorticoid. Participants who will complete the assessments at Week 52 and have achieved CRR may have the option to participate in the LTE of the study.
Intervention: Nipocalimab (Drug)
Group 3: Nipocalimab Dose 2
Participants will receive nipocalimab dose 2 IV q2w from Week 0 through Week 50 along with standard-of-care treatment of MMF or MPA and glucocorticoid. Participants who will complete the assessments at Week 52 and have achieved CRR may have the option to participate in the LTE of the study.
Intervention: Standard-of-care treatment (Drug)
Outcomes
Primary Outcomes
Percentage of Participants Achieving Complete Renal Response (CRR)
Time Frame: Week 52
Percentage of participants achieving complete renal response will be reported.
Secondary Outcomes
- Percentage of Participants Achieving CRR(Week 24)
- Percentage of Participants Achieving a Sustained Reduction in Steroid Dose Less Than or Equal to (<=)10 milligram (mg)/day of Prednisone or Equivalent(Week 16 to Week 52)
- Percentage of Participants with Treatment-emergent Adverse Events (TEAEs)(Up to Week 66)
- Percentage of Participants Achieving at Least 50 Percent (%) Decrease in Proteinuria from Baseline, Week 24 and Week 52(Baseline, Week 24 and Week 52)
- Percentage of Participants with Treatment-emergent AEs Leading to Discontinuation of Study Intervention(Up to Week 52)
- Percentage of Participants with Treatment-emergent Adverse Events of Special Interests (AESIs)(Up to Week 58)
- Percentage of Participants with Change from Baseline in Laboratory Parameters Over Time(Up to week 58)
- Percentage of Participants with Change from Baseline in Vital Sign Parameters Over Time(Up to week 58)
- Percentage of Participants with Treatment-emergent Serious Adverse Events (TESAEs)(Up to Week 66)
- Serum Concentration of Nipocalimab Over Time(Up to Week 58)
- Number of Participants with Antibodies to Nipocalimab (Anti-Drug Antibodies [ADAs] and Neutralizing Antibodies [Nabs])(Up to Week 58)