Study of Ravulizumab in Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)

Study Overview
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Brief Summary
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The objectives of this study are to evaluate the safety and efficacy of ravulizumab administered by intravenous (IV) infusion compared to placebo and demonstrate proof-of-concept of the efficacy of terminal complement inhibition in participants with LN (LN Cohort) or IgAN (IgAN Cohort).

Detailed Description
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This study consists of a 6-week Screening Period, 26-week Initial Evaluation Period, a 24-week Extension Period, and a 36-week post-treatment Follow-up Period.

Official Title
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A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants With Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)

Conditions
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Lupus Nephritis, Immunoglobulin A Nephropathy

Intervention / Treatment
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* Drug: Ravulizumab
* Drug: Placebo
* Other: Background Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Common to both disease cohorts: Proteinuria ≥1 (gram [g]/day or g/g) Vaccinated against meningococcal infection Vaccinated for Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae according to national/local regulatory requirements For LN cohort: Diagnosis of active focal or diffuse proliferative LN Class III or IV Clinically active LN, requiring/receiving immunosuppression induction treatment For IgAN cohort: Diagnosis of primary IgAN Compliance with stable and optimal dose of renin-angiotensin system inhibitor treatment for ≥ 3 months Exclusion Criteria: Common to both disease cohorts: eGFR < 30 milliliters/minute/1.73 meters squared Previously received a complement inhibitor (for example, eculizumab) Concomitant significant renal disease other than LN or IgAN History of other solid organ or bone marrow transplant Uncontrolled hypertension For IgAN cohort: Diagnosis of rapid progressive glomerulonephritis Prednisone or prednisone equivalent > 20 milligram (mg) per day for > 14 consecutive days or any other immunosuppression within 6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ravulizumab: LN Cohort<br>Eligible participants will receive ravulizumab IV infusion in combination with background therapy during both the Initial Evaluation Period (26 weeks) and Extension Period (24 weeks). During the Follow-up Period (36 weeks) participants will receive background therapy according to the standard of care. | Drug: Ravulizumab<br>* Dosages (loading and maintenance) will be based on the participant's body weight.<br>* Other names: Ultomiris;Other: Background Therapy<br>* Participants will receive background therapy consistent with the standard of care.<br>|
| Placebo Comparator: Placebo: LN Cohort<br>Eligible participants will receive placebo IV infusion in combination with background therapy during both the Initial Evaluation Period (26 weeks) and Extension Period (24 weeks). During the Follow-up Period (36 weeks) participants will receive background therapy according to the standard of care. | Drug: Placebo<br>* Dosages (loading and maintenance) will be based on the participant's body weight.<br>Other: Background Therapy<br>* Participants will receive background therapy consistent with the standard of care.<br>|
| Experimental: Ravulizumab: IgAN Cohort<br>Eligible participants will receive ravulizumab IV infusion in combination with background therapy during both the Initial Evaluation Period (26 weeks) and Extension Period (24 weeks). During the Follow-up Period (36 weeks) participants will receive background therapy according to the standard of care. | Drug: Ravulizumab<br>* Dosages (loading and maintenance) will be based on the participant's body weight.<br>* Other names: Ultomiris;Other: Background Therapy<br>* Participants will receive background therapy consistent with the standard of care.<br>|
| Placebo Comparator: Placebo: IgAN Cohort<br>Eligible participants will receive placebo IV infusion in combination with background therapy during the Initial Evaluation Period (26 weeks) and will switch to ravulizumab for the Extension Period (24 weeks). During the Follow-up Period (36 weeks) participants will receive background therapy according to the standard of care. | Drug: Ravulizumab<br>* Dosages (loading and maintenance) will be based on the participant's body weight.<br>* Other names: Ultomiris;Drug: Placebo<br>* Dosages (loading and maintenance) will be based on the participant's body weight.<br>Other: Background Therapy<br>* Participants will receive background therapy consistent with the standard of care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 26 Assessed Using 24-hour Urine Collections |  | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 50 Assessed Using 24-hour Urine Collections |  | Baseline, Week 50 | 
| Both Cohorts: Change In Estimated Glomerular Filtration Rate (eGFR) From Baseline At Week 26 And Week 50 |  | Baseline, Week 26, Week 50 | 
| LN Cohort: Percentage Of Participants Meeting The Criteria For Complete Renal Response | Complete renal response will be determined by assessing proteinuria on 24-hour urine collections, eGFR levels, and no treatment failure. | Week 26 and Week 50 | 
| LN Cohort: Percentage Of Participants Meeting The Criteria For Partial Renal Response | Partial renal response will be determined by assessing proteinuria on 24-hour urine collections, eGFR levels, and no treatment failure. | Week 26 and Week 50 | 
| LN Cohort: Time To Urine Protein To Creatinine Ratio < 0.5 g/g |  | Baseline through Week 50 | 
| LN Cohort: Percentage Of Participants Achieving Corticosteroid Taper To 7.5 mg/day |  | Week 14, Week 26, and Week 50 | 
| LN Cohort: Percentage Of Participants With Renal Flare |  | Baseline through Week 50 | 
| LN Cohort: Percentage Of Participants With Extrarenal Systemic Lupus Erythematosus Flare |  | Baseline through Week 50 | 
| IgAN Cohort: Percentage Of Participants Meeting The Criteria For Partial Remission | Partial remission will be determined by assessing proteinuria on 24-hour urine collections. | Week 26 and Week 50 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glomerulonephritis, IGA, lupus nephritis, complement C5