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NCT03841448

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

Terminated Phase 2 Results posted Last updated 9 August 2024
What this trial tests

Phase 2 trial testing Placebo in IgA Nephropathy (IgAN) in 31 participants. Terminated before completion.

Timeline
30 September 2019
Primary endpoint
17 March 2022
27 June 2023

Quick facts

Lead sponsorAlnylam Pharmaceuticals
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment31
Start date30 September 2019
Primary completion17 March 2022
Estimated completion27 June 2023
Sites17 locations across France, Malaysia, Sweden, Taiwan, United Kingdom, Philippines, Canada, Singapore

Drugs / interventions tested

Conditions studied

Sponsor

Alnylam Pharmaceuticals — full company profile →

Who can join

Adults 18 to 65, any sex, with IgA Nephropathy (IgAN) or Berger Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent Change From Baseline in UPCR as Measured in 24-hour Urine at Week 32 Primary · 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 squ

GroupValue95% CI
DBT Period: Placebo1.095± 0.258
DBT Period: Cemdisiran0.686± 0.098
Percent Change From Baseline in 24-hour Proteinuria at Week 32 Secondary · 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 correspondi

GroupValue95% CI
DBT Period: Placebo1.051± 0.266
DBT Period: Cemdisiran0.671± 0.104
Percentage of Participants With Partial Clinical Remission at Week 32 Secondary · Week 32

Partial clinical remission was defined as having UP \<1.0 g/24-hours.

GroupValue95% CI
DBT Period: Placebo0
DBT Period: Cemdisiran22.7
Percentage of Participants With >50% Reduction in 24-hour Proteinuria at Week 32 Secondary · Week 32
GroupValue95% CI
DBT Period: Placebo0
DBT Period: Cemdisiran22.7
Change From Baseline in UPCR as Measured in a Spot Urine at Week 32 Secondary · 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.

GroupValue95% CI
DBT Period: Placebo1.344± 0.139
DBT Period: Cemdisiran0.729± 0.109
Number of Participants With Change From Baseline in Hematuria at Week 32 Secondary · 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.

Post-Baseline Category: Negative
GroupValue95% CI
DBT Period: Placebo0
DBT Period: Cemdisiran4
Post-Baseline Category: Small
GroupValue95% CI
DBT Period: Placebo2
DBT Period: Cemdisiran11
Post-Baseline Category: Moderate
GroupValue95% CI
DBT Period: Placebo2
DBT Period: Cemdisiran4
Post-Baseline Category: Large
GroupValue95% CI
DBT Period: Placebo4
DBT Period: Cemdisiran1
Number of Participants With Adverse Events (AEs) Secondary · 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.

GroupValue95% CI
DBT Period: Placebo8
DBT Period: Cemdisiran19
DBT Period: Placebo + OLE Period: Cemdisiran8
DBT Period: Cemdisiran + OLE Period: Cemdisiran22
All Cemdisiran30

Adverse events — posted to ClinicalTrials.gov

Time frame: DBT Period: from the first dose of study drug up to 38 weeks. OLE Period: from Week 38 up to 88 weeks (up to 126 weeks for both periods combined). All Cemdisiran: from the first dose of study drug up to 126 weeks.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

DBT Period: Placebo
Serious: 0/9 (0%)
Deaths: 1/9
DBT Period: Cemdisiran
Serious: 1/22 (5%)
Deaths: 1/22
DBT Period: Placebo + OLE Period: Cemdisiran
Serious: 3/8 (38%)
Deaths: 0/8
DBT Period: Cemdisiran + OLE Period: Cemdisiran
Serious: 2/22 (9%)
Deaths: 1/22
All Cemdisiran
Serious: 5/30 (17%)
Deaths: 2/30

Serious adverse events (5 terms)

ReactionSystemDBT Period: PlaceboDBT Period: CemdisiranDBT Period: Placebo + OLE …DBT Period: Cemdisiran + O…All Cemdisiran
Cardiopulmonary failureCardiac disorders
Cholecystitis acuteHepatobiliary disorders
Helicobacter gastritisInfections and infestations
HyponatraemiaMetabolism and nutrition disorders
End stage renal diseaseRenal and urinary disorders
Other adverse events (122 terms — click to expand)

ReactionSystemDBT Period: PlaceboDBT Period: CemdisiranDBT Period: Placebo + OLE …DBT Period: Cemdisiran + O…All Cemdisiran
COVID-19Infections and infestations
Injection site reactionGeneral disorders
Injection site recall reactionGeneral disorders
PyrexiaGeneral disorders
Oedema peripheralGeneral disorders
RashSkin and subcutaneous tissue disorders
Upper respiratory tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
HypertensionVascular disorders
NasopharyngitisInfections and infestations
NauseaGastrointestinal disorders
UrticariaSkin and subcutaneous tissue disorders
Abdominal pain upperGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
ConjunctivitisInfections and infestations
GoutMetabolism and nutrition disorders
HeadacheNervous system disorders
HyperphosphataemiaMetabolism and nutrition disorders
InfluenzaInfections and infestations
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
Renal impairmentRenal and urinary disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
Urinary tract infectionInfections and infestations
Weight increasedInvestigations
Oral CandidiasisInfections and infestations
Ligament sprainInjury, poisoning and procedural complications
Muscle spasmsMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
Abdominal distensionGastrointestinal disorders
Abdominal painGastrointestinal disorders
Activated partial thromboplastin time prolongedInvestigations
Animal biteInjury, poisoning and procedural complications
ArthralgiaMusculoskeletal and connective tissue disorders
AstheniaGeneral disorders
Asymptomatic COVID-19Infections and infestations
Atrial fibrillationCardiac disorders
Blood pressure increasedInvestigations
BronchitisInfections and infestations

Most-reported serious reactions: Cardiopulmonary failure, Cholecystitis acute, Helicobacter gastritis, Hyponatraemia, End stage renal disease.

Data from ClinicalTrials.gov NCT03841448 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Noncoding RNA therapeutics - challenges and potential solutions.
    Winkle M, El-Daly SM, Fabbri M, Calin GA. · · 2021 · cited 1123× · PMID 34145432 · DOI 10.1038/s41573-021-00219-z
  2. Therapeutic siRNA: state of the art.
    Hu B, Zhong L, Weng Y, Peng L, et al · · 2020 · cited 991× · PMID 32561705 · DOI 10.1038/s41392-020-0207-x
  3. Therapeutic siRNA: State-of-the-Art and Future Perspectives.
    Friedrich M, Aigner A. · · 2022 · cited 256× · PMID 35997897 · DOI 10.1007/s40259-022-00549-3
  4. IgA Nephropathy: An Interesting Autoimmune Kidney Disease.
    Rajasekaran A, Julian BA, Rizk DV. · · 2021 · cited 164× · PMID 33309134 · DOI 10.1016/j.amjms.2020.10.003
  5. Paving the Road for RNA Therapeutics.
    Dammes N, Peer D. · · 2020 · cited 159× · PMID 32893005 · DOI 10.1016/j.tips.2020.08.004
  6. Glomerulonephritis: immunopathogenesis and immunotherapy.
    Anders HJ, Kitching AR, Leung N, Romagnani P. · · 2023 · cited 105× · PMID 36635359 · DOI 10.1038/s41577-022-00816-y
  7. Where should siRNAs go: applicable organs for siRNA drugs.
    Ahn I, Kang CS, Han J. · · 2023 · cited 100× · PMID 37430086 · DOI 10.1038/s12276-023-00998-y
  8. Rationale for targeting complement in COVID-19.
    Polycarpou A, Howard M, Farrar CA, Greenlaw R, et al · · 2020 · cited 98× · PMID 32559343 · DOI 10.15252/emmm.202012642

Verify or expand the search:

Other trials of Cemdisiran

Trials testing the same drug.

Other recruiting trials for IgA Nephropathy (IgAN)

Currently open trials in the same condition.

Other Alnylam Pharmaceuticals trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03841448.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing