A Study of Cemdisiran in Adults With Immunoglobulin A Nephropathy (IgAN)

Phase 2

Terminated

Conditions: IgA Nephropathy (IgAN)
Berger Disease
Glomerulonephritis, IgA

Interventions: Drug: Placebo
Drug: Cemdisiran

Registration Number: NCT03841448

Lead Sponsor: Alnylam Pharmaceuticals

Brief Summary: The purpose of this study is to evaluate the effect of cemdisiran on proteinuria in adults with immunoglobulin A nephropathy (IgAN), who excrete \>1 gram (gm) of protein per day despite standard of care, which includes treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB). These participants are at high risk for progression of kidney disease, which can result in end-stage renal failure.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 31

Inclusion Criteria

Diagnosed with primary IgAN
Currently being treated for IgAN with stable, optimal therapy, including an ACE inhibitor or ARB.
Has urine protein greater than or equal to 1 gram/24-hour
Has hematuria (blood cells present in urine)

Exclusion Criteria

Has renal disease other than IgAN
Has a diagnosis of rapidly progressive glomerulonephritis
Has a diagnosis of Henoch-Schonlein Purpura (IgA Vasculitis)
Has poor kidney function with estimated glomerular filtration rate (eGFR) <30 milliliters per minute per 1.73 meters square (mL/min/1.73 m^2)
Has known human immunodeficiency virus (HIV) infection, hepatitis C virus (HCV) infection or hepatitis B virus (HBV) infection
Has on-going high blood pressure
Treated with systemic corticosteroids for more than 7 days, or other immunosuppressant agents in the past 6 months
Received an organ transplant

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DBT Period: Placebo	Placebo	Participants received cemdisiran matching placebo, SC injection, Q4W in combination with standard of care treatment up to a maximum of 38 weeks in the DBT period.
Double-Blind Treatment (DBT) Period: Cemdisiran	Cemdisiran	Participants received cemdisiran, 600 milligrams (mg), subcutaneous (SC) injection, once every 4 weeks (Q4W) in combination with standard of care treatment up to a maximum of 38 weeks in the DBT period.
DBT Period: Cemdisiran to Open-Label Extension (OLE) Period: Cemdisiran	Cemdisiran	Participants who were randomized to receive cemdisiran in the DBT period continued receiving cemdisiran, 600 mg, SC injection, Q4W in combination with standard of care treatment up to a maximum of 88 weeks in the OLE treatment period.
DBT Period: Placebo to OLE Period: Cemdisiran	Cemdisiran	Participants who were randomized to receive cemdisiran matching placebo in the DBT period started receiving cemdisiran, 600 mg, SC injection, Q4W in combination with standard of care treatment up to a maximum of 88 weeks in the OLE treatment period.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in UPCR as Measured in 24-hour Urine at Week 32	Baseline to Week 32	UPCR is a way of assessing the amount of protein in the urine. The primary analysis for UPCR was performed using Mixed-Effect Model Repeated Measures (MMRM) approach. Geometric mean (GM)ratios were obtained by exponentially back-transforming the arithmetic mean of change in log-transformed 24h UPCR. Standard error of the mean (SEM) was calculated as exponential (mean of change in log-transformed data) \* (standard error of change in log-transformed data). Adjusted GM ratio to baseline and 90% confidence interval (CIs) were calculated by exponentially back-transforming the model-based least square (LS) mean and the corresponding 90% CI.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in 24-hour Proteinuria at Week 32	Baseline to Week 32	Proteinuria is high levels of protein in the urine. 24-hour proteinuria assessment included 24-hour urine collections to assess total protein excretion per 24 hours. Analysis was performed using the MMRM model. GM ratios were obtained by exponentially back-transforming the arithmetic mean of change in log-transformed 24h urine protein (UP). SEM was calculated as exp (mean of change in log-transformed data) \*(standard error of change in log-transformed data). Adjusted GM ratio to baseline and 90% CIs are calculated by exponentially back-transforming the model-based LS Means and the corresponding 90% CI.
Number of Participants With Adverse Events (AEs)	Up to 126 weeks	An AE is any untoward medical occurrence in a participant or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Percentage of Participants With >50% Reduction in 24-hour Proteinuria at Week 32	Week 32
Percentage of Participants With Partial Clinical Remission at Week 32	Week 32	Partial clinical remission was defined as having UP \<1.0 g/24-hours.
Change From Baseline in UPCR as Measured in a Spot Urine at Week 32	Baseline to Week 32	UPCR was calculated by dividing the level of protein in a spot urine test by the creatinine level. Analysis was performed using MMRM model. GM ratios were obtained by exponentially back-transforming the arithmetic mean of change in log-transformed spot UPCR. SEM was calculated as exp (mean of change in log-transformed data) \*(standard error of change in log-transformed data). Adjusted GM ratio to baseline and 90% CIs are calculated by exponentially back-transforming the model-based LS Means and the corresponding 90% CI.
Number of Participants With Change From Baseline in Hematuria at Week 32	Baseline to Week 32	Hematuria is the presence of blood in the urine. Hematuria from spot urine collections was evaluated to assess the effect of cemdisiran on disease course in participants. The degree of hematuria was assessed by microscopic examination of the spun urine sediment (red blood cell (RBC)/ high power field \[hpf\]) and by urine dipstick.