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

Glomerulonephritis, IgA Clinical Trial

Official title:

A Phase 2, Randomized, Double-blind, Placebo-controlled Study of Cemdisiran in Adult Patients With IgA Nephropathy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03841448
• Other study ID #: ALN-CC5-005
• Secondary ID: 2018-002716-27
• Status: Terminated
• Phase: Phase 2
• Start date: September 30, 2019
• Est. completion date: June 27, 2023

Study information

• Verified date: December 2023
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 31
• Est. completion date: June 27, 2023
• Est. primary completion date: March 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Berger Disease
• Glomerulonephritis
• Glomerulonephritis, IGA
• IgA Nephropathy (IgAN)
• Kidney Diseases

Intervention

Drug:
• Placebo
Normal saline (0.9% NaCl) matching volume of cemdisiran doses were administered SC.
• Cemdisiran
Cemdisiran was administered by SC injection.

Locations

Country	Name	City	State
Canada	Clinical Trial Site	Brampton	Ontario
Canada	Clinical Trial Site	Toronto	Ontario
Canada	Clinical Trial Site	Vancouver	British Columbia
France	Clinical Trial Site	Grenoble
France	Clinical Trial Site	La Tronche
France	Clinical Trial Site	Mulhouse
Malaysia	Clinical Trial Site	Kuala Lumpur
Malaysia	Clinical Trial Site	Kuantan
Malaysia	Clinical Trial Site	Serdang
Philippines	Clinical Trial Site	Quezon City
Singapore	Clinical Trial Site	Singapore
Spain	Clinical Trial Site	Córdoba
Spain	Clinical Trial Site	Girona
Sweden	Clinical Trial Site	Huddinge
Sweden	Clinical Trial Site	Uppsala
Taiwan	Clinical Trial Site	Taichung
United Kingdom	Clinical Trial Site	Leicester

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

Canada,  France,  Malaysia,  Philippines,  Singapore,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in UPCR as Measured in 24-hour Urine at 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.	Baseline to Week 32
Secondary	Percent Change From Baseline in 24-hour Proteinuria at 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.	Baseline to Week 32
Secondary	Percentage of Participants With Partial Clinical Remission at Week 32	Partial clinical remission was defined as having UP <1.0 g/24-hours.	Week 32
Secondary	Percentage of Participants With >50% Reduction in 24-hour Proteinuria at Week 32		Week 32
Secondary	Change From Baseline in UPCR as Measured in a Spot Urine at 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.	Baseline to Week 32
Secondary	Number of Participants With Change From Baseline in Hematuria at 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.	Baseline to Week 32
Secondary	Number of Participants With Adverse Events (AEs)	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.	Baseline up to 240 weeks