Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)Phase 3NCT02319005
ENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)
A Phase 3 study testing Revusiran (ALN-TTRSC) and Sterile Normal Saline (0.9% NaCl) in people with Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC) and Amyloidosis, Hereditary, run by Alnylam Pharmaceuticals at 61 sites in 9 countries.
Trial summary
The purpose of this study was to evaluate the safety and efficacy of revusiran (ALN-TTRSC) in patients with transthyretin (TTR) mediated Familial Amyloidotic Cardiomyopathy. Dosing has been discontinued; patients are being followed-up for safety. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC), Amyloidosis, Hereditary, Amyloid Neuropathies, Familial
- What is being tested?
- Revusiran (ALN-TTRSC) and Sterile Normal Saline (0.9% NaCl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 206 participants
- Where
- 61 sitesin 9 countries
- Study dates
- Dec 2014to 30 Mar 2017
- Phase
- Phase 3
- 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented TTR mutation
- Amyloid deposits in cardiac or non-cardiac tissue
- Medical history of heart failure
- Evidence of cardiac involvement by echocardiogram
Who cannot join
- Has known primary amyloidosis (AL), leptomeningeal amyloidosis, non-FAC hereditary cardiomyopathy, hypertensive cardiomyopathy, or cardiomyopathy due to valvular heart disease
- Has known peripheral vascular disease affecting ambulation
- Has a Polyneuropathy Disability score >2
- Has a New York Heart Association (NYHA) classification of IV
Trial locations and contacts
61 sites in 9 countries.
61 sites in 9 countries
United States41 sites
Clinical Trial Site
Atlanta, Georgia
Clinical Trial Site
Aurora, Colorado
Clinical Trial Site
Bakersfield, California
Clinical Trial Site
Baltimore, Maryland, 21201
Clinical Trial Site
Baltimore, Maryland, 21287
Clinical Trial Site
Beverly Hills, California
Clinical Trial Site
Boston, Massachusetts, 02111
Clinical Trial Site
Boston, Massachusetts, 02118
Clinical Trial Site
Boston, Massachusetts, 02215
Clinical Trial Site
Charleston, South Carolina
Clinical Trial Site
Chicago, Illinois, 60611
Clinical Trial Site
Chicago, Illinois, 60612
Clinical Trial Site
Chicago, Illinois, 60637
Clinical Trial Site
Cleveland, Ohio, 44106
Clinical Trial Site
Cleveland, Ohio, 44195
Clinical Trial Site
Columbus, Ohio
Clinical Trial Site
Dallas, Texas
Clinical Trial Site
Detroit, Michigan
Clinical Trial Site
Durham, North Carolina
Clinical Trial Site
Fort Worth, Texas
Clinical Trial Site
Houston, Texas
Clinical Trial Site
La Mesa, California
Clinical Trial Site
Los Angeles, California
Clinical Trial Site
Nashville, Tennessee
Clinical Trial Site
New Orleans, Louisiana
Clinical Trial Site
New York, New York
Clinical Trial Site
Newark, New Jersey
Clinical Trial Site
Philadelphia, Pennsylvania, 19102
Clinical Trial Site
Philadelphia, Pennsylvania, 19104
Clinical Trial Site
Richmond, Virginia
Clinical Trial Site
Rochester, Minnesota
Clinical Trial Site
Rosedale, New York
Clinical Trial Site
San Francisco, California
Clinical Trial Site
Seattle, Washington
Clinical Trial Site
St Louis, Missouri
Clinical Trial Site
Stanford, California
Clinical Trial Site
Tampa, Florida
Clinical Trial Site
The Bronx, New York
Clinical Trial Site
Torrance, California
Clinical Trial Site
Washington D.C., District of Columbia, 20037
Clinical Trial Site
Washington D.C., District of Columbia, 20422
France4 sites
Clinical Trial Site
Bordeaux, Aquitaine
Clinical Trial Site
Créteil
Clinical Trial Site
Marseille
Clinical Trial Site
Paris
Belgium3 sites
Clinical Trial Site
Anderlecht
Clinical Trial Site
Hasselt
Clinical Trial Site
Roeselare
Italy3 sites
Clinical Trial Site
Bologna
Clinical Trial Site
Messina
Clinical Trial Site
Pavia
Spain3 sites
Clinical Trial Site
Barcelona, 8003
Clinical Trial Site
Barcelona, 8907
Clinical Trial Site
Madrid
United Kingdom3 sites
Clinical Trial Site
Croydon, England
Clinical Trial Site
London, England
Clinical Trial Site
Tooting
About this study
Official title: A Phase 3 Multicenter, Multinational, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ALN TTRSC in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)
The purpose of this study was to evaluate the safety and efficacy of revusiran (ALN-TTRSC) in patients with transthyretin (TTR) mediated Familial Amyloidotic Cardiomyopathy. Dosing has been discontinued; patients are being followed-up for safety.
- Conditions
- Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC), Amyloidosis, Hereditary, Amyloid Neuropathies, Familial, Amyloid Neuropathies, Amyloidosis, Hereditary, Transthyretin-Related, Familial Transthyretin Cardiac Amyloidosis
- Being tested
- Revusiran (ALN-TTRSC), Sterile Normal Saline (0.9% NaCl)
- Keywords
- Cardiomyopathy, Heart Failure, FAC, Amyloid, Transthyretin, TTR, RNAi therapeutic
- Medical subject headings
- Amyloidosis, Familial, Amyloid Neuropathies, Familial, Amyloid Neuropathies, Amyloidosis, Hereditary, Transthyretin-Related, Cardiomyopathies, Heart Failure, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Revusiran (ALN-TTRSC)Drug
Sterile Normal Saline (0.9% NaCl)Drug
| Study group | Role | What they receive |
|---|---|---|
| Revusiran (ALN-TTRSC) | Active comparator | administered by subcutaneous (SC) injection Receives: Drug: Revusiran (ALN-TTRSC) |
| Sterile Normal Saline (0.9% NaCl) | Placebo comparator | administered by subcutaneous (SC) injection Receives: Drug: Sterile Normal Saline (0.9% NaCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
6 Minute Walk Distance (6-MWD)
The difference between revusiran and placebo group in change from baseline to 18 months in the total distance walked in 6 minutes
Measured: 18 months
Serum TTR Levels
The difference between revusiran (ALN-TTRSC) and placebo group in the percent reduction in serum TTR levels over 18 months
Measured: 18 months
Secondary outcomes (6)
Composite Cardiovascular (CV) Mortality and Cardiovascular (CV) Hospitalization
Number of cardiovascular-related deaths and cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
Measured: 18 months
New York Heart Association (NYHA) Class
The difference between revusiran (ALN-TTRSC) and placebo group in the change from baseline to 18 months in the NYHA class
Measured: 18 months
Kansas City Cardiomyopathy Questionnaire (KCCQ)
The difference between revusiran (ALN-TTRSC) and placebo group in the change from Baseline to 18 months in the Kansas City Cardiomyopathy Questionnaire
Measured: 18 months
Cardiovascular (CV) Mortality
Number of cardiovascular-related deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
Measured: 18 months
Cardiovascular (CV) Hospitalization
Number of cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
Measured: 18 months
All-cause Mortality
Total number of deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2014 (estimated)
- Study startDec 2014
- Primary completion30 Mar 2017
- Study completion30 Mar 2017
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 206 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jared Gollob, MD, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02319005
- Sponsor's protocol ID
- ALN-TTRSC-004
- Status last verified
- Jun 2018
- First submitted
- 12 Dec 2014
- Last updated
- 18 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Judge DP, Kristen AV, Grogan M, Maurer MS, Falk RH, Hanna M, Gillmore J, Garg P, Vaishnaw AK, Harrop J, Powell C, Karsten V, Zhang X, Sweetser MT, Vest J, Hawkins PN. Phase 3 Multicenter Study of Revusiran in Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis with Cardiomyopathy (ENDEAVOUR). Cardiovasc Drugs Ther. 2020 Jun;34(3):357-370. doi: 10.1007/s10557-019-06919-4.
PubMed 32062791
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Multicenter, Multinational, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ALN TTRSC in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)
- ClinicalTrials.gov ID
- NCT02319005
- Acronym / sponsor ID
- ALN-TTRSC-004
- Conditions
- Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC), Amyloidosis, Hereditary, Amyloid Neuropathies, Familial, Amyloid Neuropathies, Amyloidosis, Hereditary, Transthyretin-Related, Familial Transthyretin Cardiac Amyloidosis
- Keywords
- Cardiomyopathy, Heart Failure, FAC, Amyloid, Transthyretin, TTR, RNAi therapeutic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 206 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2014
- Primary completion
- 30 Mar 2017 (actual)
- Study completion
- 30 Mar 2017 (actual)
- First posted
- 18 Dec 2014 (estimated)
- Results
- Posted 18 Jul 2018
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 was to evaluate the safety and efficacy of revusiran (ALN-TTRSC) in patients with transthyretin (TTR) mediated Familial Amyloidotic Cardiomyopathy. Dosing has been discontinued; patients are being followed-up for safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Revusiran (ALN-TTRSC) | Active comparator | Drug: Revusiran (ALN-TTRSC)administered by subcutaneous (SC) injection |
| Sterile Normal Saline (0.9% NaCl) | Placebo comparator | Drug: Sterile Normal Saline (0.9% NaCl)administered by subcutaneous (SC) injection |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Documented TTR mutation
- Amyloid deposits in cardiac or non-cardiac tissue
- Medical history of heart failure
- Evidence of cardiac involvement by echocardiogram
Key exclusion criteria (4 listed)
- Has known primary amyloidosis (AL), leptomeningeal amyloidosis, non-FAC hereditary cardiomyopathy, hypertensive cardiomyopathy, or cardiomyopathy due to valvular heart disease
- Has known peripheral vascular disease affecting ambulation
- Has a Polyneuropathy Disability score >2
- Has a New York Heart Association (NYHA) classification of IV
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 |
|---|---|---|
| Revusiran (ALN-TTRSC) | Drug | Revusiran (ALN-TTRSC) |
| Sterile Normal Saline (0.9% NaCl) | Drug | Sterile Normal Saline (0.9% NaCl) |
Primary outcome
6 Minute Walk Distance (6-MWD)
Time frame: 18 months
The difference between revusiran and placebo group in change from baseline to 18 months in the total distance walked in 6 minutes
Serum TTR Levels
Time frame: 18 months
The difference between revusiran (ALN-TTRSC) and placebo group in the percent reduction in serum TTR levels over 18 months
6 secondary outcomes
Composite Cardiovascular (CV) Mortality and Cardiovascular (CV) Hospitalization
Time frame: 18 months
New York Heart Association (NYHA) Class
Time frame: 18 months
Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time frame: 18 months
Cardiovascular (CV) Mortality
Time frame: 18 months
Cardiovascular (CV) Hospitalization
Time frame: 18 months
All-cause Mortality
Time frame: 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32062791Judge DP, Kristen AV, Grogan M, Maurer MS, Falk RH, Hanna M, Gillmore J, Garg P, Vaishnaw AK, Harrop J, Powell C, Karsten V, Zhang X, Sweetser MT, Vest J, Hawkins PN. Phase 3 Multicenter Study of Revusiran in Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis with Cardiomyopathy (ENDEAVOUR). Cardiovasc Drugs Ther. 2020 Jun;34(3):357-370. doi: 10.1007/s10557-019-06919-4.
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.
Jared Gollob, MD study director
Alnylam Pharmaceuticals
61 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Revusiran (ALN-TTRSC) and Sterile Normal Saline (0.9% NaCl) in people with Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC) and Amyloidosis, Hereditary, run by Alnylam Pharmaceuticals at 61 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 4 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: finished, as of the sponsor's last update on 18 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 61 sites in United States, France, Belgium, Italy, Spain 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 18 Jul 2018). 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?
6 Minute Walk Distance (6-MWD) (time frame: 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02319005, which also lists 1 linked publication.
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 18 Jul 2018.