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

December 7, 2023 updated by: Alnylam Pharmaceuticals

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
        • Clinical Trial Site
    • Ontario
      • Brampton, Ontario, Canada, L6T0G1
        • Clinical Trial Site
      • Toronto, Ontario, Canada, M5G2C4
        • Clinical Trial Site
  • France
      • Grenoble, France
        • Clinical Trial Site
      • La Tronche, France
        • Clinical Trial Site
      • Mulhouse, France
        • Clinical Trial Site
  • Malaysia
      • Kuala Lumpur, Malaysia
        • Clinical Trial Site
      • Kuantan, Malaysia
        • Clinical Trial Site
      • Serdang, Malaysia
        • Clinical Trial Site
  • Philippines
      • Quezon City, Philippines
        • Clinical Trial Site
  • Singapore
      • Singapore, Singapore
        • Clinical Trial Site
  • Spain
      • Córdoba, Spain
        • Clinical Trial Site
      • Girona, Spain
        • Clinical Trial Site
  • Sweden
      • Huddinge, Sweden
        • Clinical Trial Site
      • Uppsala, Sweden
        • Clinical Trial Site
  • Taiwan
      • Taichung, Taiwan
        • Clinical Trial Site
  • United Kingdom
      • Leicester, United Kingdom
        • Clinical Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Double-Blind Treatment (DBT) Period: 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.
Drug: Cemdisiran
Cemdisiran was administered by SC injection.
Other Names:
  • ALN-CC5
Placebo Comparator: DBT Period: 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.
Drug: Placebo
Normal saline (0.9% NaCl) matching volume of cemdisiran doses were administered SC.
Experimental: DBT Period: Cemdisiran to Open-Label Extension (OLE) Period: 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.
Drug: Cemdisiran
Cemdisiran was administered by SC injection.
Other Names:
  • ALN-CC5
Placebo Comparator: DBT Period: Placebo to OLE Period: 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.
Drug: Cemdisiran
Cemdisiran was administered by SC injection.
Other Names:
  • ALN-CC5

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline in UPCR as Measured in 24-hour Urine at Week 32
Time Frame: 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.
Baseline to Week 32

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alnylam Pharmaceuticals

Investigators

  • Study Director: Medical Director, Alnylam Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2019

Primary Completion (Actual)

March 17, 2022

Study Completion (Actual)

June 27, 2023

Study Registration Dates

First Submitted

February 13, 2019

First Submitted That Met QC Criteria

February 13, 2019

First Posted (Actual)

February 15, 2019

Study Record Updates

Last Update Posted (Actual)

December 8, 2023

Last Update Submitted That Met QC Criteria

December 7, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALN-CC5-005
  • 2018-002716-27 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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