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)
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 123
- Locations
- 1
- Primary Endpoint
- Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 26 Assessed Using 24-hour Urine Collections
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Masking Description
Participants, all investigative site personnel, and any Alexion employee, or designee, directly associated with the conduct of the study will be blinded to participant treatment assignments during the 26-week Initial Evaluation Period. Both the participants and the investigative site personnel will remain blinded for the remaining 24-week Extension Period.
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Ravulizumab: LN Cohort
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.
Intervention: Ravulizumab (Drug)
Ravulizumab: LN Cohort
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.
Intervention: Background Therapy (Other)
Placebo: LN Cohort
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.
Intervention: Placebo (Drug)
Placebo: LN Cohort
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.
Intervention: Background Therapy (Other)
Ravulizumab: IgAN Cohort
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.
Intervention: Ravulizumab (Drug)
Ravulizumab: IgAN Cohort
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.
Intervention: Background Therapy (Other)
Placebo: IgAN Cohort
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.
Intervention: Ravulizumab (Drug)
Placebo: IgAN Cohort
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.
Intervention: Placebo (Drug)
Placebo: IgAN Cohort
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.
Intervention: Background Therapy (Other)
Outcomes
Primary Outcomes
Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 26 Assessed Using 24-hour Urine Collections
Time Frame: Baseline, Week 26
Secondary Outcomes
- 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)
- 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)
- 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)
- LN Cohort: Percentage Of Participants With Extrarenal Systemic Lupus Erythematosus Flare(Baseline through Week 50)