A Study to Evaluate the Efficacy and Safety of ION-682884 in Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)

JRCT ID: jRCT2061220044

Registered date:15/07/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Transthyretin-mediated amyloid cardiomyopathy (ATTR CM)
• Date of first enrollment: 05/10/2022
• Target sample size: 20
• Countries of recruitment: Argentina,Japan,Australia,Japan,Austria,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,Czechia,Japan,Denmark,Japan,France,Japan,Germany,Japan,Greece,Japan,Israel,Japan,Italy,Japan,Poland,Japan,Portugal,Japan,Spain,Japan,Sweden,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Experimental: ION-682884
ION-682884 by subcutaneous injection once every 4 weeks
Placebo Comparator: Placebo
Matching placebo by subcutaneous injection once every 4 weeks

Outcome(s)

• Primary Outcome: Composite outcome of CV-death and recurrent CV clinical events at the end of study

Secondary Outcome

- Change From Baseline in the 6MWT Distance at Week 121
Note: 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 121
Note: 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 distinct domains and two 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.

- CV Clinical Events at the end of the study
- CV death at the end of the study
- All-Cause death at the end of the study

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 90age old
• Gender: Both

Include 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
- End-diastolic interventricular septum thickness of > 12 mm on Screening echocardiogram
- New York Heart Association (NYHA) class I-III

Exclude 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 alterations in immunoglobulin free light chain (FLC) ratio, unless fat, bone marrow, or heart biopsy confirming the absence of light chain and the presence of TTR protein 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 with or without ursodeoxycholic acid, and/or non-dihydropyridine calcium-channel blocker. Patients receiving any of these agents must respect a wash-out period of 14 days before randomization

Related Information

• Primary Sponsor: Viney Nick
• Source(s) of Monetary Support: Astra Zeneca, AB
• Secondary ID(s): NCT04136171,2019-002835-27