EPIC-ATTR: A Study to Evaluate the Effect of Eplontersen on the Transthyretin Reduction and Long-term Safety in Chinese Subjects With Transthyretin Amyloid Cardiomyopathy

NCT06194825 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: D8450C00005
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 26

Brief Summary

The purpose of this study is to investigate the effect of eplontersen compared to placebo on the reduction of serum TTR concentration and long-term safety in Chinese participants with hereditary or wild-type transthyretin amyloid cardiomyopathy.

Conditions

Transthyretin Amyloid Cardiomyopathy

Keywords

Eplontersen; ATTR-CM

Outcome Measures

Primary Outcomes (1)

• Percent change of serum TTR concentration from baseline

  To evaluate the effect of eplontersen compared to placebo on serum transthyretin (TTR) concentration up to 24 weeks

  up to 24 weeks

Secondary Outcomes (4)

• Changes from baseline in NT-proBNP serum level

  up to 24 weeks

• Changes from baseline in hs-cTnT serum level

  up to 24 weeks

• Plasma concentrations of eplontersen at specified time-points (Week0,2,4,8,12,16,20,24,28,32,36,48,60,72,84,96,104)

  up to 124 weeks

• Plasma concentrations of anti-drug antibodies (ADA) at specified time-points (Week0,2,4,8,12,16,20,24,28,32,36,48,60,72,84,96,104,114,124)

  up to 124 weeks

Study Arms (2)

Eplontersen

EXPERIMENTAL

Eplontersen by subcutaneous injection once every 4 weeks

Drug: Eplontersen

placebo

PLACEBO COMPARATOR

Eplontersen-matching placebo by subcutaneous injection once every 4 weeks

Drug: Placebo

Interventions

Eplontersen DRUG

Eplontersen by subcutaneous injection

Eplontersen

Placebo DRUG

Eplontersen-matching placebo by subcutaneous injection

placebo

Eligibility Criteria

• Age: 20 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
• to 90 years of age (inclusive).
• Females: must be non-pregnant and non-lactating and either:
• surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy);
• post-menopausal (defined as 12 months of spontaneous amenorrhea in females \> 55 years of age or, in females ≤ 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and FSH levels in the post-menopausal range for the laboratory involved);
• abstinent\* or,
• if engaged in sexual relations of child-bearing potential, agree to use 1 highly effective contraceptive method from the time of signing the informed consent form until at least 24 weeks after the last dose of study intervention (eplontersen or placebo).
• Males must be surgically sterile or abstinent\*; if engaged in sexual relations with a female of child-bearing potential, the participant must be using an acceptable contraceptive method from the time of signing the informed consent form until at least 24 weeks after the last dose of study intervention.
• A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, hormonal methods etc.
• \*Abstinence is only acceptable as true abstinence, i.e., when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial and withdrawal are not acceptable methods of contraception.
• Willing to be genetically tested for mutations in the TTR gene before study intervention administration, if it was not done before.
• 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 99mTc-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.
• Medical history of HF secondary to hereditary or wild-type ATTR-CM with at least:
• prior hospitalization for HF, which may include hospitalization for arrhythmia or pacemaker/implantable cardioverter defibrillator placement, or

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Acute coronary syndrome, unstable angina, stroke, TIA, coronary revascularization, cardiac device implantation, cardiac valve repair, or major surgery within 3 months prior or during screening.
• Hospitalization or urgent visit to emergency department/emergency room for worsening of HF with discharge date within 4 weeks prior to or during screening.
• Uncontrolled hypertension (systolic BP \> 160 mmHg or diastolic BP \> 100 mmHg).
• Uncontrolled clinically significant cardiac arrhythmia, per investigator's assessment (e.g., no pacemaker, although indicated).
• Severe uncorrected cardiac valvular disease.
• Cardiomyopathy not primarily caused by ATTR-CM, for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease.
• Alanine aminotransferase/aspartate aminotransferase (ALT/AST) \> 2.0 × ULN.
• Total bilirubin ≥ 2.0 × ULN (participants with total bilirubin ≥ 2.0 × ULN may be allowed on study if indirect bilirubin only is elevated, ALT/AST is not greater than the ULN and known to have Gilbert's disease OR if, in the opinion of the investigator, the bilirubin abnormality is deemed not clinically significant, pending proper follow-up with the local specialist and discussion with Medical Monitor).
• Platelets \< 125 × 109/L.
• Urine protein creatinine ratio (UPCR) ≥ 750 mg/g. In the event of UPCR above this threshold ineligibility may be confirmed by a repeat random spot UPCR UPCR ≥ 750 mg/g.
• Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2 at screening (CKD EPI formula \[Levey et al. 2009\]). If the eGFR is thought to be underestimated, the CKD EPI creatinine-cystatin C equation can be used for confirmation (Inker et al. 2012).
• Abnormal thyroid function tests with clinical significance per investigator's judgement.
• Serum retinol level at screening \< Lower Limit of Normal (LLN). Unless, after ophthalmologist consultation, the investigator considers the retinol level below LLN not clinical relevant. In this case the participant may be considered to be eligible, pending a discussion with the Medical Monitor. (This criterion does not apply to ATTRv-CM patients with known mutation at the position 84 \[e.g., Ile84Ser\]).
• Hemoglobin A1c (HbA1c) \> 9.5%.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (26)

Research Site

Beijing, 100029, China

Location

Research Site

Beijing, 100034, China

Location

Research Site

Beijing, 100037, China

Location

Research Site

Beijing, 100191, China

Location

Research Site

Beijing, 100730, China

Location

Research Site

Changsha, 410008, China

Location

Research Site

Changsha, 410013, China

Location

Research Site

Changsha, 430033, China

Location

Research Site

Chengdu, 610041, China

Location

Research Site

Chengdu, 610072, China

Location

Research Site

Chongqing, 400010, China

Location

Research Site

Chongqing, 400042, China

Location

Research Site

Guangzhou, 510062, China

Location

Research Site

Guangzhou, 510100, China

Location

Research Site

Hangzhou, 310003, China

Location

Research Site

Hangzhou, 310014, China

Location

Research Site

Hangzhou, 310052, China

Location

Research Site

Ha’erbin, 150001, China

Location

Research Site

Jinan, 250001, China

Location

Research Site

Nanchang, 330006, China

Location

Research Site

Shanghai, 200032, China

Location

Research Site

Suzhou, 215006, China

Location

Research Site

Taiyuan, 030001, China

Location

Research Site

Wuhan, 430030, China

Location

Research Site

Wuhan, 430060, China

Location

Research Site

Xi'an, 710061, China

Location

MeSH Terms

Interventions

eplontersen

Study Officials

• Shuyang Zhang, MD

  Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The treatment assignment of the 24-week double-blind treatment phase will be kept blinded to sponsor until the end of double-blind treatment phase and kept blinded to participants and investigators until the end of study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Eligible participants will be randomized in a 3:1 ratio to either eplontersen or placebo in the double-blind treatment phase, followed by the open label treatment phase (participants initially assigned to placebo will switch to eplontersen treatment from Week 24), to evaluate long term safety and tolerability of eplontersen treatment.

Study Record Dates

• First Submitted: December 5, 2023
• First Posted: January 8, 2024
• Study Start: December 1, 2023
• Primary Completion: May 13, 2026
• Study Completion (Estimated): January 5, 2027
• Last Updated: June 9, 2026

Record last verified: 2026-05

Locations

CN (26)