NCT02319005

Brief 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.

Trial Health

93
On Track

Trial Health Score

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

Enrollment
206

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Dec 2014

Geographic Reach
9 countries

61 active sites

Status
completed

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

Study Start

First participant enrolled

December 1, 2014

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

December 12, 2014

Completed
6 days until next milestone

First Posted

Study publicly available on registry

December 18, 2014

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 30, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 30, 2017

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

July 18, 2018

Completed
Last Updated

July 18, 2018

Status Verified

June 1, 2018

Enrollment Period

2.3 years

First QC Date

December 12, 2014

Results QC Date

March 27, 2018

Last Update Submit

June 22, 2018

Conditions

Keywords

CardiomyopathyHeart FailureFACAmyloidTransthyretinTTRRNAi therapeutic

Outcome Measures

Primary Outcomes (2)

  • 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

    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

    18 months

Secondary Outcomes (6)

  • Composite Cardiovascular (CV) Mortality and Cardiovascular (CV) Hospitalization

    18 months

  • New York Heart Association (NYHA) Class

    18 months

  • Kansas City Cardiomyopathy Questionnaire (KCCQ)

    18 months

  • Cardiovascular (CV) Mortality

    18 months

  • Cardiovascular (CV) Hospitalization

    18 months

  • +1 more secondary outcomes

Study Arms (2)

Revusiran (ALN-TTRSC)

ACTIVE COMPARATOR

administered by subcutaneous (SC) injection

Drug: Revusiran (ALN-TTRSC)

Sterile Normal Saline (0.9% NaCl)

PLACEBO COMPARATOR

administered by subcutaneous (SC) injection

Drug: Sterile Normal Saline (0.9% NaCl)

Interventions

Revusiran (ALN-TTRSC)
Sterile Normal Saline (0.9% NaCl)

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Documented TTR mutation
  • Amyloid deposits in cardiac or non-cardiac tissue
  • Medical history of heart failure
  • Evidence of cardiac involvement by echocardiogram

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (61)

Clinical Trial Site

Bakersfield, California, United States

Location

Clinical Trial Site

Beverly Hills, California, United States

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Clinical Trial Site

La Mesa, California, United States

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Los Angeles, California, United States

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San Francisco, California, United States

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Stanford, California, United States

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Torrance, California, United States

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Aurora, Colorado, United States

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Clinical Trial Site

Washington D.C., District of Columbia, 20037, United States

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Clinical Trial Site

Washington D.C., District of Columbia, 20422, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, 60611, United States

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Chicago, Illinois, 60612, United States

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Chicago, Illinois, 60637, United States

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New Orleans, Louisiana, United States

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Baltimore, Maryland, 21201, United States

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Baltimore, Maryland, 21287, United States

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Boston, Massachusetts, 02111, United States

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Boston, Massachusetts, 02118, United States

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Boston, Massachusetts, 02215, United States

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Detroit, Michigan, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Newark, New Jersey, United States

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New York, New York, United States

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Rosedale, New York, United States

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The Bronx, New York, United States

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Durham, North Carolina, United States

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Cleveland, Ohio, 44106, United States

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Cleveland, Ohio, 44195, United States

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Columbus, Ohio, United States

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Philadelphia, Pennsylvania, 19102, United States

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Clinical Trial Site

Philadelphia, Pennsylvania, 19104, United States

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Charleston, South Carolina, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Richmond, Virginia, United States

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Seattle, Washington, United States

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Anderlecht, Belgium

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Hasselt, Belgium

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Roeselare, Belgium

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Toronto, Canada

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Bordeaux, Aquitaine, France

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Créteil, France

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Marseille, France

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Paris, France

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Heidelberg, Germany

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Münster, Germany

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Bologna, Italy

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Messina, Italy

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Pavia, Italy

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Barcelona, 8003, Spain

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Barcelona, 8907, Spain

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Madrid, Spain

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Umeå, Sweden

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Croydon, England, United Kingdom

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London, England, United Kingdom

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Clinical Trial Site

Tooting, United Kingdom

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Related Publications (1)

  • 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.

MeSH Terms

Conditions

Amyloidosis, FamilialAmyloid Neuropathies, FamilialAmyloid NeuropathiesAmyloidosis, Hereditary, Transthyretin-RelatedCardiomyopathiesHeart FailureAlzheimer Disease

Interventions

revusiran

Condition Hierarchy (Ancestors)

Metabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolic DiseasesNutritional and Metabolic DiseasesAmyloidosisProteostasis DeficienciesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesNervous System DiseasesPeripheral Nervous System DiseasesNeuromuscular DiseasesHeart DiseasesCardiovascular DiseasesDementiaBrain DiseasesCentral Nervous System DiseasesTauopathiesNeurocognitive DisordersMental Disorders

Limitations and Caveats

While dosing of patients was discontinued early, a protocol amendment allowed additional safety follow-up visits. Per the new assessment schedule, this study did not meet the criteria of a Terminated study, as additional follow-up visits occurred.

Results Point of Contact

Title
Chief Medical Officer
Organization
Alnylam Pharmaceuticals Inc

Study Officials

  • Jared Gollob, MD

    Alnylam Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 12, 2014

First Posted

December 18, 2014

Study Start

December 1, 2014

Primary Completion

March 30, 2017

Study Completion

March 30, 2017

Last Updated

July 18, 2018

Results First Posted

July 18, 2018

Record last verified: 2018-06

Locations