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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.

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/.

Condition or disease Intervention/treatment Phase
Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM) Drug: AKCEA-TTR-LRx Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 750 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : March 13, 2020
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AKCEA-TTR-LRx
ACKEA-TTR-LRx by subcutaneous injection once every 4 weeks
Drug: AKCEA-TTR-LRx
ACKEA-TTR-LRx by subcutaneous injection
Other Name: ION-682884

Placebo Comparator: Placebo
Matching placebo by subcutaneous injection once every 4 weeks
Drug: Placebo
Matching placebo by subcutaneous injection




Primary Outcome Measures :
  1. 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'

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.


  3. Rate of CV Mortality at Week 120 [ Time Frame: Baseline to Week 120 ]
  4. Rate of CV Clinical Events at Week 120 [ Time Frame: Baseline to Week 120 ]
  5. Rate of All-Cause Mortality at Week 120 [ Time Frame: Baseline to Week 120 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT04136171


Contacts
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Contact: Ionis Pharmaceuticals 800-679-4747 patients@ionisph.com

Locations
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Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
Akcea Therapeutics
Additional Information:
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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04136171    
Other Study ID Numbers: ION-682884-CS2
2019-002835-27 ( EudraCT Number )
First Posted: October 23, 2019    Key Record Dates
Last Update Posted: November 13, 2020
Last Verified: November 2020
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
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Ionis Pharmaceuticals, Inc.:
TTR
Amyloidosis
Cardiomyopathy
Additional relevant MeSH terms:
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Cardiomyopathies
Amyloidosis
Heart Diseases
Cardiovascular Diseases
Proteostasis Deficiencies
Metabolic Diseases