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CARDIO-TTRansform: A Study to Evaluate the Efficacy and Safety of AKCEA-TTR-LRx in Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)

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ClinicalTrials.gov Identifier: NCT04136171
Recruitment Status : Recruiting
First Posted : October 23, 2019
Last Update Posted : November 13, 2020
Sponsor:
Collaborator:
Akcea Therapeutics
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE October 21, 2019
First Posted Date  ICMJE October 23, 2019
Last Update Posted Date November 13, 2020
Actual Study Start Date  ICMJE March 13, 2020
Estimated Primary Completion Date January 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 21, 2019)
  • Composite Outcome of Cardiovascular (CV) Mortality and frequency of CV clinical events at Week 120 [ Time Frame: Baseline to Week 120 ]
    This composite measure is based on the Finkelstein-Shoenfeld method, with each participant compared with every other participant in a pairwise manner. The test assigns a +1 or a -1 to a participant based on each participant's CV clinical events or mortality. The test statistic is based on the sum of these scores and will be stratified by the stratification factors. The mortality and CV clinical events in all analyses, unless otherwise specified, will be adjudicated by an independent CAC using the '2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials'
  • Change From Baseline on the 6-Minute Walk Test (6MWT) at Week 61 [ Time Frame: Baseline to Week 61 ]
    The 6MWT is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6MWT provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2019)
  • Change From Baseline in the 6MWT Distance at Week 120 [ Time Frame: Baseline to Week 120 ]
    The 6MWT is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6MWT provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions.
  • Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Week 120 [ Time Frame: Baseline to Week 120 ]
    The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item self-administered questionnaire developed to independently measure the patient's perception of their health status, which includes heart failure symptoms, impact on physical and social function, and how their heart failure impacts their quality of life (QOL) within a 2-week recall period. The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores. KCCQ responses are provided along a rating scale continuum with equal spacing from worst to best, with a higher score equaling a better score.
  • Rate of CV Mortality at Week 120 [ Time Frame: Baseline to Week 120 ]
  • Rate of CV Clinical Events at Week 120 [ Time Frame: Baseline to Week 120 ]
  • Rate of All-Cause Mortality at Week 120 [ Time Frame: Baseline to Week 120 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CARDIO-TTRansform: A Study to Evaluate the Efficacy and Safety of AKCEA-TTR-LRx in Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
Official Title  ICMJE A Phase 3 Global, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ION-682884 in Patients With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
Brief Summary To evaluate the efficacy of AKCEA-TTR-LRx compared to placebo for 120 weeks in patients with ATTR-CM receiving available standard of care (SoC). For more information, please visit https://www.cardio-ttransform.com/.
Detailed Description This is a multicenter, double-blind study in up to 750 participants, who will be randomized to receive subcutaneous (SC) injections of either AKCEA-TTR-LRx or placebo once every 4 weeks. Participants will also receive daily supplemental doses of the recommended daily allowance of vitamin A.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
Intervention  ICMJE
  • Drug: AKCEA-TTR-LRx
    ACKEA-TTR-LRx by subcutaneous injection
    Other Name: ION-682884
  • Drug: Placebo
    Matching placebo by subcutaneous injection
Study Arms  ICMJE
  • Experimental: AKCEA-TTR-LRx
    ACKEA-TTR-LRx by subcutaneous injection once every 4 weeks
    Intervention: Drug: AKCEA-TTR-LRx
  • Placebo Comparator: Placebo
    Matching placebo by subcutaneous injection once every 4 weeks
    Intervention: Drug: Placebo
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: October 21, 2019)
750
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date January 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal or abstinent. If engaged in sexual relations of child-bearing potential, agree to use 1 highly effective contraceptive method
  • Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the participant or the participant's non-pregnant female partner must be using a highly effective contraceptive method
  • Amyloid deposits in cardiac or non-cardiac tissue confirmed by Congo Red (or equivalent) staining OR technetium scintigraphy (99mTc -3,3-diphosphono-1,2- propanodicarboxylic acid [DPD-Tc], 99m Tc-pyrophosphate [PYP-Tc], or 99m Tc-hydroxymethylene-diphosphonate [HMDP-Tc]) with Grade 2 or 3 cardiac uptake in the absence of abnormal light chains ratio, centrally confirmed
  • End-diastolic interventricular septum thickness of > 12 mm on Screening echocardiogram
  • New York Heart Association (NYHA) class I-III

Exclusion Criteria:

  • Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac device implantation, cardiac valve repair, or major surgery within 3 months of Screening
  • Cardiomyopathy not primarily caused by ATTR-CM, for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease
  • Monoclonal gammopathy of undetermined significance (MGUS) and/or immunoglobulin free light chain ratio < 0.26 and > 1.65, unless fat, bone marrow, or heart biopsy confirming the absence of light chain by mass spectrometry or immunoelectron microscopy
  • Prior liver or heart transplant, and/or Left Ventricular Assist Device (LVAD) or anticipated liver transplant or LVAD within 1 year after randomization
  • Current or previous treatment with Tegsedi™ (inotersen) or Onpattro™ (patisiran) or other oligonucleotide or RNA therapeutic (including siRNA)
  • Current treatment with diflunisal, doxycycline, and/or calcium-channel blocker. Participants receiving any of these agents must respect a wash-out period of 14 days before randomization.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ionis Pharmaceuticals 800-679-4747 patients@ionisph.com
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   Germany,   Greece,   Israel,   Italy,   Portugal,   Spain,   Sweden,   United States
Removed Location Countries Brazil
 
Administrative Information
NCT Number  ICMJE NCT04136171
Other Study ID Numbers  ICMJE ION-682884-CS2
2019-002835-27 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ionis Pharmaceuticals, Inc.
Study Sponsor  ICMJE Ionis Pharmaceuticals, Inc.
Collaborators  ICMJE Akcea Therapeutics
Investigators  ICMJE Not Provided
PRS Account Ionis Pharmaceuticals, Inc.
Verification Date November 2020

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