Study of Ravulizumab in Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)
Phase 2
Active, not recruiting
- Conditions
- Lupus NephritisImmunoglobulin A Nephropathy
- Interventions
- Registration Number
- NCT04564339
- Lead Sponsor
- Alexion Pharmaceuticals, Inc.
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 123
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo: IgAN Cohort Placebo 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. Ravulizumab: LN Cohort Background Therapy 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. Placebo: LN Cohort Placebo 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. Placebo: LN Cohort Background Therapy 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. Ravulizumab: IgAN Cohort Background Therapy 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. Placebo: IgAN Cohort Background Therapy 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. Ravulizumab: LN Cohort Ravulizumab 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. Ravulizumab: IgAN Cohort Ravulizumab 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. Placebo: IgAN Cohort Ravulizumab 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.
- Primary Outcome Measures
Name Time Method Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 26 Assessed Using 24-hour Urine Collections Baseline, Week 26
- Secondary Outcome Measures
Name Time Method 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 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 Meeting The Criteria For Partial Renal Response Week 26 and Week 50 Partial renal response will be determined by assessing proteinuria on 24-hour urine collections, eGFR levels, and no treatment failure.
Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 50 Assessed Using 24-hour Urine Collections Baseline, Week 50 LN Cohort: Percentage Of Participants Meeting The Criteria For Complete Renal Response Week 26 and Week 50 Complete renal response will be determined by assessing proteinuria on 24-hour urine collections, eGFR levels, and no treatment failure.
LN Cohort: Time To Urine Protein To Creatinine Ratio < 0.5 g/g Baseline through Week 50 IgAN Cohort: Percentage Of Participants Meeting The Criteria For Partial Remission Week 26 and Week 50 Partial remission will be determined by assessing proteinuria on 24-hour urine collections.
LN Cohort: Percentage Of Participants With Extrarenal Systemic Lupus Erythematosus Flare Baseline through Week 50
Trial Locations
- Locations (1)
Research Site
🇬🇧Salford, United Kingdom