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).
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
123
Dosages (loading and maintenance) will be based on the participant's body weight.
Dosages (loading and maintenance) will be based on the participant's body weight.
Participants will receive background therapy consistent with the standard of care.
IgAN Cohort: Percentage Change From Baseline in Proteinuria at Week 26 Measured by Absolute Protein (Based on 24-hour Urine Collections)
Proteinuria, the presence of excess proteins in the urine, was measured by absolute protein in grams/day derived from 24-hour urine collections obtained at designated timepoints. A negative change from baseline indicated a reduction in symptoms.
Time frame: Baseline, Week 26
LN Cohort: Percentage Change From Baseline in Proteinuria at Week 26 Measured by Urine Protein to Creatinine Ratio (UPCR) (Based on 24-hour Urine Collections)
Proteinuria, the presence of excess proteins in the urine, was measured by UPCR in grams/gram derived from 24-hour urine collections obtained at designated timepoints. A negative change from baseline indicated a reduction in symptoms.
Time frame: Baseline, Week 26
IgAN Cohort: Percentage Change From Baseline in Proteinuria at Week 50 Measured by Absolute Protein (Based on 24-hour Urine Collections)
Proteinuria, the presence of excess proteins in the urine, was measured by absolute protein in grams/day derived from 24-hour urine collections obtained at designated timepoints. A negative change from baseline indicated a reduction in symptoms.
Time frame: Baseline, Week 50
LN Cohort: Percentage Change From Baseline in Proteinuria at Week 50 Measured by UPCR (Based on 24-hour Urine Collections)
Proteinuria, the presence of excess proteins in the urine, was measured by UPCR in grams/gram derived from 24-hour urine collections obtained at designated timepoints. A negative change from baseline indicated a reduction in symptoms.
Time frame: Baseline, Week 50
IgAN Cohort: Percentage of Participants With > 30% and > 50% Reduction in Proteinuria at Week 26 and Week 50 Compared to Baseline Assessed Using 24-hour Urine Collections
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Research Site
San Dimas, California, United States
Research Site
Santa Monica, California, United States
Research Site
South Gate, California, United States
Research Site
Stanford, California, United States
Research Site
Orlando, Florida, United States
Research Site
Plantation, Florida, United States
Research Site
Lawrenceville, Georgia, United States
Research Site
Lexington, Kentucky, United States
Research Site
Louisville, Kentucky, United States
Research Site
Boston, Massachusetts, United States
...and 54 more locations
Proteinuria, the presence of excess proteins in the urine, was measured by absolute protein in grams/day derived from 24-hour urine collections obtained at designated timepoints.
Time frame: Baseline to Week 26 and Week 50
LN Cohort: Percentage of Participants With > 30% and > 50% Reduction in Proteinuria at Week 26 and Week 50 Compared to Baseline Assessed Using 24-hour Urine Collections
Proteinuria, the presence of excess proteins in the urine, was measured by UPCR in grams/gram derived from 24-hour urine collections obtained at designated timepoints.
Time frame: Baseline to Week 26 and Week 50
IgAN Cohort: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 26 and Week 50
Changes in kidney function were monitored using measurements of eGFR and calculated based on the Chronic Kidney Disease Epidemiology Collaboration formula. Results are reported in milliliters/minute/1.73 meters squared (mL/min/1.73 m\^2). Estimates of change from baseline are least-square means based on a mixed-effect model for repeated measures model that included change from baseline as the response variable, treatment as independent variable and adjusts for covariates of baseline and the stratification factor at randomization. An increase in eGFR in response to treatment indicated a reduction in symptoms.
Time frame: Baseline, Week 26 and Week 50
LN Cohort: Change From Baseline in eGFR at Week 26 and Week 50
Changes in kidney function were monitored using measurements of eGFR and calculated based on the Chronic Kidney Disease Epidemiology Collaboration formula. Results are reported in mL/min/1.73 m\^2. Estimates of change from baseline are least-square means based on a mixed-effect model for repeated measures model that included change from baseline as the response variable, treatment as independent variable and adjusts for covariates of baseline and the stratification factor at randomization. An increase in eGFR in response to treatment indicated a reduction in symptoms.
Time frame: Baseline, Week 26 and Week 50
IgAN Cohort: Change From Baseline in Serum Complement Component 3 (C3) and Complement Component 4 (C4) Concentrations at Week 26 and Week 50
Time frame: Baseline, Week 26 and Week 50
LN Cohort: Change From Baseline in Serum C3 and C4 Concentrations at Week 26 and Week 50
Time frame: Baseline, Week 26 and Week 50
LN Cohort: Percentage of Participants Meeting the Criteria for Complete Renal Response (CRR)
The CRR was defined as meeting all 3 of the following criteria: - UPCR ≤0.5 gram/gram (g/g); - eGFR \>60 mL/min/1.73 m\^2 or no eGFR reduction ≥20% from baseline; and - no treatment failure. Treatment failure was defined as the receipt of additional standard of care therapy at any time during the study for protocol-defined renal flare, severe extrarenal systemic lupus erythematosus (SLE) flare, or suboptimal response.
Time frame: Week 26 and Week 50
LN Cohort: Percentage of Participants Meeting the Criteria for Partial Renal Response (PRR)
The PRR was defined as meeting all 3 of the following criteria: - decrease of UPCR \>50% from baseline; - eGFR \>60 mL/min/1.73 m\^2 or no eGFR reduction ≥20% from baseline; and - no treatment failure. Treatment failure was defined as the receipt of additional standard of care therapy at any time during the study for protocol-defined renal flare, severe extrarenal SLE flare, or suboptimal response.
Time frame: Week 26 and Week 50
LN Cohort: Time to Urine Protein to Creatinine Ratio (UPCR) < 0.5 g/g, as Measured by Spot Urine Samples
Time frame: Baseline through Week 50
LN Cohort: Percentage of Participants Achieving Corticosteroid Taper to 7.5 Milligrams (mg)/Day
A corticosteroid taper was carried out per protocol at the clinical discretion of the investigator.
Time frame: Week 14, Week 26, and Week 50
LN Cohort: Percentage of Participants With Renal Flare
Renal flare was determined in the opinion of the investigator and additional protocol-specified criteria. For participants who achieved a CRR, a renal flare was the reproducible recurrence of proteinuria ≥1g/g. For all other participants, a renal flare was either of the following: a reproducible increase of serum creatinine \>25% higher than baseline, above the upper limit of normal (plus additional protocol-specified criteria), or a reproducible doubling of the UPCR from a 24-hour urine collection compared with the lowest previous value obtained after the first dose of study intervention.
Time frame: Baseline through Week 50
LN Cohort: Percentage of Participants With Extrarenal Systemic Lupus Erythematosus (SLE) Flare
Extrarenal SLE flare was defined as an increase in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Safety of Estrogens in Lupus Erythematosus National Assessment modification ≥4 points that was not accounted for by proteinuria, hematuria, urinary cellular casts, hypocomplementemia, or an increase in anti-double-stranded DNA antibody level. The SLEDAI-2K is an instrument that was used to assess the disease activity of extrarenal SLE flare across 18 disease descriptors. Each descriptor carried a weighted value ranging from 1-8, with the reported score calculated as the sum of these descriptors and ranging from 0 to 85. Higher scores represent increased degrees of disease activity.
Time frame: Baseline through Week 50
LN Cohort: Percentage of Participants With Treatment Failure
Treatment failure was defined as the receipt of additional standard of care therapy at any time during the study for protocol-defined renal flare, severe extrarenal SLE flare, or suboptimal response.
Time frame: Baseline through Week 50
LN Cohort: Percentage of Participants With Suboptimal Response
A suboptimal response was to be determined in the opinion of the investigator in addition to the following criterion: reproducible proteinuria ≤25% decreased compared to baseline based on UPCR on a 24-hour urine collection performed by a central laboratory.
Time frame: Baseline through Week 50
LN Cohort: Change From Baseline in Serum Albumin at Week 26 and Week 50
For the determination of serum albumin, blood samples were obtained at designated time points.
Time frame: Baseline, Week 26, Week 50
IgAN Cohort: Percentage of Participants Meeting the Criteria for Partial Remission
Partial remission was defined as mean proteinuria \<1 g/24 hours, based on two valid 24-hour urine collections obtained within 2 weeks prior to the study visit.
Time frame: Week 26 and Week 50