Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03997383
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03997383
Recruitment Status : Recruiting
First Posted : June 25, 2019
Last Update Posted : November 16, 2020
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE June 24, 2019
First Posted Date  ICMJE June 25, 2019
Last Update Posted Date November 16, 2020
Actual Study Start Date  ICMJE September 4, 2019
Estimated Primary Completion Date October 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 24, 2019)
Change from Baseline at Month 12 in Six-Minute Walk Test (6-MWT) [ Time Frame: Baseline, Month 12 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2020)
  • 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.
  • Composite Endpoint of All-Cause Mortality, Frequency of Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) 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 events (CV hospitalizations and HF visits) and change from baseline in 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.
  • Composite Endpoint of All-Cause Mortality and Frequency of All-Cause Hospitalizations and Urgent HF Visits [ Time Frame: Up to Month 12 ]
    The hazard rate of all-cause mortality and all-cause hospitalizations and urgent HF visits will be compared between treatment groups using an Andersen-Gill model.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2019)
  • 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.
  • 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.
  • 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.
  • Change from Baseline in Serum Transthyretin (TTR) Levels [ Time Frame: Up to Month 12 ]
  • Maximum Plasma Concentration at End of Infusion (Cmax) of Patisiran [ Time Frame: Post-dose up to Month 12 ]
  • Thirty-minute Post-infusion Concentration (Cp[30min]) of Patisiran [ Time Frame: Post-dose up to Month 12 ]
  • Pre-infusion Concentration (Cmin) of Patisiran [ Time Frame: Pre-dose up to Month 12 ]
  • Number of Participants with Anti-drug Antibodies (ADAs) [ Time Frame: Up to Month 12 ]
  • Frequency of Adverse Events [ Time Frame: Up to Month 25 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE APOLLO-B: A Study to Evaluate Patisiran in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
Official Title  ICMJE 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)
Brief Summary The purpose of this study is to evaluate the efficacy and safety of patisiran in participants with ATTR amyloidosis with cardiomyopathy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Patisiran
    Participants will be administered multiple doses of patisiran in the double-blind and open-label extension period.
    Intervention: Drug: Patisiran
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: Patisiran
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 24, 2019)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 1, 2022
Estimated Primary Completion Date October 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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, >300 ng/L and <8500 ng/L; in patients with permanent or persistent atrial fibrillation, screening NT-proBNP> 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Argentina,   Australia,   Brazil,   Czechia,   Denmark,   France,   Hong Kong,   Italy,   Japan,   Korea, Republic of,   Mexico,   Poland,   Portugal,   Sweden,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03997383
Other Study ID Numbers  ICMJE ALN-TTR02-011
2019-001458-24 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Alnylam Pharmaceuticals
Study Sponsor  ICMJE Alnylam Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Alnylam Pharmaceuticals
PRS Account Alnylam Pharmaceuticals
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP