The Efficacy and Safety of Atacicept in Combination With Mycophenolate Mofetil Used to Treat Lupus Nephritis

Study Overview
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Brief Summary
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The purpose of this study is to learn whether atacicept treatment leads to improvement in kidney function in subjects with active lupus nephritis in combination with mycophenolate mofetil (MMF) and corticosteroids. The study was sponsored by Merck Serono International; operational oversight was provided by ZymoGenetics.

Official Title
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A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Atacicept in Subjects With Lupus Nephritis in Combination With Mycophenolate Mofetil Therapy.

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Atacicept
* Drug: Mycophenolate mofetil
* Drug: Placebo
* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of systemic lupus erythematosus (SLE) satisfying at least 4 out of the 11 American College of Rheumatology (ACR) criteria (Appendix B) Renal biopsy performed consistent with active International Society of Nephrology/Renal Pathology Society (ISN/PRS) class III or IV lupus nephritis Exclusion Criteria: Estimated glomerular filtration rate (GFR) less than or equal to (<=) 30 milliliter per minute (mL/min) per 1.73 square meter (m^2) Active central nervous system SLE deemed to be severe or progressive and/or associated with significant cognitive impairment Any treatment with MMF, azathioprine, or cyclophosphamide within the last 6 months, or known hypersensitivity to MMF or atacicept. Any prior treatment with abatacept, rituximab, belimumab, or other B cell modulating agents.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atacicept Plus Mycophenolate mofetil Plus Corticosteroids<br> | Drug: Atacicept<br>* Atacicept will be administered at a dose of 150 milligram (mg) subcutaneously (SC) twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks.<br>Drug: Mycophenolate mofetil<br>* MMF will be administered orally with a starting dose of 500 mg twice daily for 1 week, will be increased to 1000 mg twice daily for 1 week, then it will be adjusted to 1500 mg or lower twice daily as per investigator's discretion.<br>Drug: Corticosteroids<br>* High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever is less will be administered for 4 Weeks and will be tapered to 7.5 to 10 mg/day up to Week 12.<br>|
| Placebo Comparator: Placebo Plus Mycophenolate mofetil Plus Corticosteroids<br> | Drug: Mycophenolate mofetil<br>* MMF will be administered orally with a starting dose of 500 mg twice daily for 1 week, will be increased to 1000 mg twice daily for 1 week, then it will be adjusted to 1500 mg or lower twice daily as per investigator's discretion.<br>Drug: Placebo<br>* Placebo will be administered at a dose of 150 mg SC twice weekly for 4 weeks followed by 150 mg SC once weekly for 48 weeks.<br>Drug: Corticosteroids<br>* High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever is less will be administered for 4 Weeks and will be tapered to 7.5 to 10 mg/day up to Week 12.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Confirmed Complete Renal Response (CRR), Partial Response, and Non-response | Complete renal response (CRR): from baseline, a return to within 10% of normal for renal function (assessed by calculated glomerular filtration rate [GFR]), improvement in proteinuria (urine protein/creatinine ratio <0.5) & resolution of hematuria. Partial response (PR): from baseline, a <= 10% worsening in renal function ( by calculated GFR); 50% improvement in proteinuria (assessed by urine protein/creatinine ratio) & resolution of hematuria, Non-response (NR): Neither criteria for CR or PR was met. Subjects were also deemed NR if they had treatment failure, regardless of CR or PR status. Subjects cannot be treatment failures. A response of CRR was confirmed if the Week 52 value is CRRand if the Week 48 value is CRR and at least 4 weeks apart from Week 52 /if the Week 48 value was missing/ less than 4 weeks from Week 52, then the Week 56 response must be CRR - if the Week 52 value was missing, then Week 48 and Week 56 must be CRR. | At Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Normalization of Renal Function |  | At Week 52 | 
| Number of Participants With New Lupus Flares |  | At Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nephritis, atacicept