NCT03841448

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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
31

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Sep 2019

Typical duration for phase_2

Geographic Reach
9 countries

17 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 13, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 15, 2019

Completed
8 months until next milestone

Study Start

First participant enrolled

September 30, 2019

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 17, 2022

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 27, 2023

Completed
5 months until next milestone

Results Posted

Study results publicly available

December 8, 2023

Completed
Last Updated

August 9, 2024

Status Verified

June 1, 2024

Enrollment Period

2.5 years

First QC Date

February 13, 2019

Results QC Date

September 12, 2023

Last Update Submit

August 2, 2024

Conditions

IgA Nephropathy (IgAN)Berger DiseaseGlomerulonephritis, IgA

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (6)

  • Percent Change From Baseline in 24-hour Proteinuria at Week 32

    Baseline to Week 32

  • Percentage of Participants With Partial Clinical Remission at Week 32

    Week 32

  • Percentage of Participants With >50% Reduction in 24-hour Proteinuria at Week 32

    Week 32

  • Change From Baseline in UPCR as Measured in a Spot Urine at Week 32

    Baseline to Week 32

  • Number of Participants With Change From Baseline in Hematuria at Week 32

    Baseline to Week 32

  • +1 more secondary outcomes

Study Arms (4)

Double-Blind Treatment (DBT) Period: Cemdisiran

EXPERIMENTAL

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

DBT Period: Placebo

PLACEBO COMPARATOR

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

DBT Period: Cemdisiran to Open-Label Extension (OLE) Period: Cemdisiran

EXPERIMENTAL

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

DBT Period: Placebo to OLE Period: Cemdisiran

PLACEBO COMPARATOR

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

Interventions

PlaceboDRUG

Normal saline (0.9% NaCl) matching volume of cemdisiran doses were administered SC.

DBT Period: Placebo
CemdisiranDRUG

Cemdisiran was administered by SC injection.

Also known as: ALN-CC5
DBT Period: Cemdisiran to Open-Label Extension (OLE) Period: CemdisiranDBT Period: Placebo to OLE Period: CemdisiranDouble-Blind Treatment (DBT) Period: Cemdisiran

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

Clinical Trial Site

Vancouver, British Columbia, Canada

Location

Clinical Trial Site

Brampton, Ontario, L6T0G1, Canada

Location

Clinical Trial Site

Toronto, Ontario, M5G2C4, Canada

Location

Clinical Trial Site

Grenoble, France

Location

Clinical Trial Site

La Tronche, France

Location

Clinical Trial Site

Mulhouse, France

Location

Clinical Trial Site

Kuala Lumpur, Malaysia

Location

Clinical Trial Site

Kuantan, Malaysia

Location

Clinical Trial Site

Serdang, Malaysia

Location

Clinical Trial Site

Quezon City, Philippines

Location

Clinical Trial Site

Singapore, Singapore

Location

Clinical Trial Site

Córdoba, Spain

Location

Clinical Trial Site

Girona, Spain

Location

Clinical Trial Site

Huddinge, Sweden

Location

Clinical Trial Site

Uppsala, Sweden

Location

Clinical Trial Site

Taichung, Taiwan

Location

Clinical Trial Site

Leicester, United Kingdom

Location

MeSH Terms

Conditions

Glomerulonephritis, IGA

Condition Hierarchy (Ancestors)

GlomerulonephritisNephritisKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesAutoimmune DiseasesImmune System Diseases

Results Point of Contact

Title
Chief Medical Officer
Organization
Alnylam Pharmaceuticals Inc
Clinicaltrials@alnylam.com
866-330-0326

Study Officials

  • Medical Director

    Alnylam Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 13, 2019

First Posted

February 15, 2019

Study Start

September 30, 2019

Primary Completion

March 17, 2022

Study Completion

June 27, 2023

Last Updated

August 9, 2024

Results First Posted

December 8, 2023

Record last verified: 2024-06

Data Sharing

IPD Sharing
Will not share

Locations

PH(1)TW(1)GB(1)FR(3)SE(2)MY(3)CA(3)SG(1)ES(2)