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Trial record 18 of 359 for:    transthyretin

APOLLO-B: A Study to Evaluate Patisiran in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)

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ClinicalTrials.gov Identifier: NCT03997383
Recruitment Status : Not yet recruiting
First Posted : June 25, 2019
Last Update Posted : June 25, 2019
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of patisiran in participants with ATTR amyloidosis with cardiomyopathy.

Condition or disease Intervention/treatment Phase
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy Drug: Placebo Drug: Patisiran Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: APOLLO-B: A Phase 3, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Patisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : October 1, 2021
Estimated Study Completion Date : November 1, 2022


Arm Intervention/treatment
Experimental: Patisiran
Participants will be administered multiple doses of patisiran in the double-blind and open-label extension period.
Drug: Patisiran
Patisiran will be administered by intravenous (IV) infusion.
Other Names:
  • ALN-TTR02
  • patisiran-LNP

Placebo Comparator: Placebo
Participants will be administered multiple doses of placebo in the double-blind period. In the open-label extension period, participants will be administered multiple doses of patisiran.
Drug: Placebo
Normal saline (0.9% NaCl) matching volume of patisiran doses will be administered intravenously.

Drug: Patisiran
Patisiran will be administered by intravenous (IV) infusion.
Other Names:
  • ALN-TTR02
  • patisiran-LNP




Primary Outcome Measures :
  1. Change from Baseline at Month 12 in Six-Minute Walk Test (6-MWT) [ Time Frame: Baseline, Month 12 ]

Secondary Outcome Measures :
  1. Change from Baseline at Month 12 in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score [ Time Frame: Baseline, Month 12 ]
    The KCCQ is a 23-item self-administered questionnaire quantifying 6 domains (symptoms, physical function, quality of life, social limitation, self-efficacy, and symptom stability) and 2 summary scores (clinical and overall summary [OS]). Scores are transformed to a range of 0-100, in which higher scores reflect better health status.

  2. Composite Endpoint of All-Cause Mortality, Frequency of Cardiovascular (CV)-Related Hospitalizations and Change from Baseline in 6-MWT [ Time Frame: Up to Month 12 ]
    This composite endpoint will be analyzed using the win ratio method. This method combines all-cause mortality, frequency of CV-related hospitalizations, and change from baseline in 6-Minute Walk Test (6-MWT) in a hierarchical fashion. The method uses pairwise comparisons for all possible active/placebo patient pairs. A 'win' represents a patient doing better based on the hierarchical comparison. The win ratio is the total number of 'winners' divided by the total number of 'losers' in the active group.

  3. Composite Endpoint of All-Cause Mortality and Frequency of All-Cause Hospitalizations [ Time Frame: Up to Month 12 ]
    The hazard rate of all-cause mortality and all-cause hospitalizations will be compared between treatment groups using an Andersen-Gill model.

  4. Change from Baseline in Serum Transthyretin (TTR) Levels [ Time Frame: Up to Month 12 ]
  5. Maximum Plasma Concentration at End of Infusion (Cmax) of Patisiran [ Time Frame: Post-dose up to Month 12 ]
  6. Thirty-minute Post-infusion Concentration (Cp[30min]) of Patisiran [ Time Frame: Post-dose up to Month 12 ]
  7. Pre-infusion Concentration (Cmin) of Patisiran [ Time Frame: Pre-dose up to Month 12 ]
  8. Number of Participants with Anti-drug Antibodies (ADAs) [ Time Frame: Up to Month 12 ]
  9. Frequency of Adverse Events [ Time Frame: Up to Month 25 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented diagnosis of ATTR amyloidosis with cardiomyopathy, classified as either hereditary ATTR amyloidosis with cardiomyopathy or wild-type ATTR amyloidosis with cardiomyopathy
  • Medical history of heart failure with at least 1 prior hospitalization for heart failure, or current clinical evidence (signs and symptoms of heart failure)
  • Clinically stable with no cardiovascular related hospitalizations within 6 weeks of study start
  • Has never taken tafamidis before (tafamidis naïve) or currently on tafamidis for ≥6 months with evidence of disease progression while on tafamidis treatment
  • Able to complete ≥150 m on the 6-minute walk test
  • Screening N-terminal pro B-type natriuretic peptide (NT-proBNP), a blood marker of heart failure severity, > 600 ng/L and <8500 ng/L

Exclusion Criteria:

  • Known primary amyloidosis (AL) or leptomeningeal amyloidosis.
  • Received prior TTR lowering treatment
  • New York Heart Association heart failure classification of III and at high risk
  • New York Heart Association heart failure classification of IV
  • Neuropathy requiring cane or stick to walk, or is wheelchair bound
  • Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2
  • Abnormal liver function
  • Has hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
  • Has non-amyloid disease that significantly affects ability to walk (e.g., severe chronic obstructive pulmonary disease, severe arthritis, or peripheral vascular disease affecting ambulation)
  • Prior or planned heart, liver, or other organ transplant
  • Other cardiomyopathy not related to ATTR amyloidosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03997383


Contacts
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Contact: Alnylam Clinical Trial Information Line 1-877-ALNYLAM clinicaltrials@alnylam.com
Contact: Alnylam Clinical Trial Information Line 1-877-256-9526 clinicaltrials@alnylam.com

Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
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Study Director: John Vest, MD Alnylam Pharmaceuticals

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Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03997383     History of Changes
Other Study ID Numbers: ALN-TTR02-011
2019-001458-24 ( EudraCT Number )
First Posted: June 25, 2019    Key Record Dates
Last Update Posted: June 25, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alnylam Pharmaceuticals:
RNAi therapeutic
Transthyretin
TTR
Amyloidosis
Cardiomyopathy
ATTR

Additional relevant MeSH terms:
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Amyloid Neuropathies, Familial
Cardiomyopathies
Amyloidosis
Heart Diseases
Cardiovascular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Amyloid Neuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn
Amyloidosis, Familial
Metabolism, Inborn Errors