IgA Nephropathy (IgAN)Phase 2NCT03841448
A Study of Cemdisiran in Adults With Immunoglobulin A Nephropathy (IgAN)
A Phase 2 study testing Cemdisiran in people with IgA Nephropathy (IgAN) and Berger Disease, run by Alnylam Pharmaceuticals at 17 sites in 9 countries.
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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- IgA Nephropathy (IgAN), Berger Disease, Glomerulonephritis, IgA
- What is being tested?
- Cemdisiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 17 sitesin 9 countries
- Study dates
- 30 Sep 2019to 27 Jun 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
17 sites in 9 countries.
17 sites in 9 countries
Canada3 sites
Clinical Trial Site
Brampton, Ontario, L6T0G1
Clinical Trial Site
Toronto, Ontario, M5G2C4
Clinical Trial Site
Vancouver, British Columbia
France3 sites
Clinical Trial Site
Grenoble
Clinical Trial Site
La Tronche
Clinical Trial Site
Mulhouse
Malaysia3 sites
Clinical Trial Site
Kuala Lumpur
Clinical Trial Site
Kuantan
Clinical Trial Site
Serdang
About this study
Official title: 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.
- Being tested
- Placebo, Cemdisiran
- Medical subject headings
- Glomerulonephritis, IGA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Normal saline (0.9% NaCl) matching volume of cemdisiran doses were administered SC.
CemdisiranDrug
Also called ALN-CC5
Cemdisiran was administered by SC injection.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Cemdisiran |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Week 32
Secondary outcomes (6)
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.
Measured: Baseline to Week 32
Percentage of Participants With Partial Clinical Remission at Week 32
Partial clinical remission was defined as having UP <1.0 g/24-hours.
Measured: Week 32
Percentage of Participants With >50% Reduction in 24-hour Proteinuria at Week 32
Measured: Week 32
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.
Measured: Baseline to Week 32
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.
Measured: Baseline to Week 32
Number of Participants With Adverse Events (AEs)
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.
Measured: Up to 126 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2019
- Study start30 Sep 2019
- Primary completion17 Mar 2022
- Study completion27 Jun 2023
Why it stopped: Study was terminated early having identified clinically meaningful magnitude of proteinuria reduction due to cemdisiran (study goal). Participants completed DBT period\&were in OLE period. Sponsor had no concerns with safety\&integrity of participants.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for IgA Nephropathy (IgAN)Studies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03841448
- Sponsor's protocol ID
- ALN-CC5-005
- Other IDs
- 2018-002716-27, 2018
- Status last verified
- Jun 2024
- First submitted
- 13 Feb 2019
- Last updated
- 9 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-blind, Placebo-controlled Study of Cemdisiran in Adult Patients With IgA Nephropathy
- ClinicalTrials.gov ID
- NCT03841448
- Acronym / sponsor ID
- ALN-CC5-005
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated early having identified clinically meaningful magnitude of proteinuria reduction due to cemdisiran (study goal). Participants completed DBT period\&were in OLE period. Sponsor had no concerns with safety\&integrity of participants.
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 30 Sep 2019 (actual)
- Primary completion
- 17 Mar 2022 (actual)
- Study completion
- 27 Jun 2023 (actual)
- First posted
- 15 Feb 2019 (actual)
- Results
- Posted 8 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Double-Blind Treatment (DBT) Period: Cemdisiran | Experimental | Drug: CemdisiranParticipants 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: Placebo | Placebo comparator | Drug: PlaceboParticipants 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. |
| DBT Period: Cemdisiran to Open-Label Extension (OLE) Period: Cemdisiran | Experimental | Drug: CemdisiranParticipants 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 | Placebo comparator | Drug: CemdisiranParticipants 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboNormal saline (0.9% NaCl) matching volume of cemdisiran doses were administered SC. | Drug | DBT Period: Placebo |
| CemdisiranAlso: ALN-CC5Cemdisiran was administered by SC injection. | Drug | DBT Period: Cemdisiran to Open-Label Extension (OLE) Period: Cemdisiran, DBT Period: Placebo to OLE Period: Cemdisiran, Double-Blind Treatment (DBT) Period: Cemdisiran |
Primary outcome
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.
6 secondary outcomes
Percent Change From Baseline in 24-hour Proteinuria at Week 32
Time frame: Baseline to Week 32
Percentage of Participants With Partial Clinical Remission at Week 32
Time frame: Week 32
Percentage of Participants With >50% Reduction in 24-hour Proteinuria at Week 32
Time frame: Week 32
Change From Baseline in UPCR as Measured in a Spot Urine at Week 32
Time frame: Baseline to Week 32
Number of Participants With Change From Baseline in Hematuria at Week 32
Time frame: Baseline to Week 32
Number of Participants With Adverse Events (AEs)
Time frame: Up to 126 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Alnylam Pharmaceuticals
17 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cemdisiran in people with IgA Nephropathy (IgAN) and Berger Disease, run by Alnylam Pharmaceuticals at 17 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Canada, France, Malaysia, Spain, Sweden and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline in UPCR as Measured in 24-hour Urine at Week 32 (time frame: Baseline to Week 32). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2024.