A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending and Multiple Doses of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Healthy Japanese Participants

NCT04302064 | Completed Phase 1 FDA Drug

• 1 other identifier: ION-682884-CS20
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and tolerability of single and potentially multiple doses of Eplontersen administered subcutaneously (SC) to healthy Japanese participants.

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity

  Up to 92 days

• Percentage of Participants with TEAEs Potentially Related to Study Drug

  Up to 92 days

• Percentage of Participants with Changes in Clinically Significant (CS) Laboratory Value Abnormalities

  Up to 92 days

Study Arms (2)

Eplontersen

EXPERIMENTAL

Single dose on Day 1 or multiple doses (every 4 weeks for 12 weeks) of Eplontersen administered SC.

Drug: Eplontersen

Placebo

PLACEBO COMPARATOR

Single dose on Day 1 or multiple doses (every 4 weeks for 12 weeks) of Eplontersen-matching placebo administered SC.

Drug: Placebo

Interventions

Eplontersen DRUG

Eplontersen administered SC

Also known as: ION-682884, AKCEA-TTR-LRx, IONIS-TTR-LRx

Eplontersen

Placebo DRUG

Eplontersen-matching placebo administered SC

Placebo

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• 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
• Healthy Japanese males or females of non-childbearing potential, aged 20 to 65 inclusive at the time of informed consent defined as being of first- or second-generation ethnic origin with each set of parents qualifying as Japanese under the prior generation. Generations will be defined as follows:
• First generation Japanese participants must be born in Japan, cannot have lived outside of Japan for more than 10 years, must maintain Japanese diet, culture and lifestyle and parents and both sets of grandparents are of Japanese origin
• Second-generation Japanese are participants who are born outside of Japan to the first-generation Japanese parents
• Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or post-menopausal (defined as 12 months of spontaneous amenorrhea without an alternative medical cause and follicle-stimulating hormone (FSH) levels in the postmenopausal range for the laboratory involved 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 91 days (single-dose cohorts) or 13 weeks (multiple-dose cohorts) after the last dose of Study Drug (Eplontersen or placebo)
• \* 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.
• Willingness to take vitamin A supplements

You may not qualify if:

• Clinically significant abnormalities in medical history (e.g., previous acute coronary syndrome within 6 months of Screening, major surgery within 3 months of Screening) or physical examination
• Random spot urine protein/creatinine (P/C) ratio (UPCR) ≥ 200 milligrams per gram (mg/g).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, alkaline phosphatase (ALP), serum creatinine, blood urea nitrogen (BUN) \> upper limit of normal (ULN)
• Fasting blood glucose \> ULN
• Platelet count \< lower limit of normal (LLN)
• Uncontrolled hypertension (blood pressure \[BP\] \> 160/100 millimeters of mercury \[mm Hg\])
• Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (1)

WCCT Global

Cypress, California, 90630, United States

Location

Related Publications (1)

• Diep JK, Yu RZ, Viney NJ, Schneider E, Guo S, Henry S, Monia B, Geary R, Wang Y. Population pharmacokinetic/pharmacodynamic modelling of eplontersen, an antisense oligonucleotide in development for transthyretin amyloidosis. Br J Clin Pharmacol. 2022 Dec;88(12):5389-5398. doi: 10.1111/bcp.15468. Epub 2022 Aug 7.

  PMID: 35869634 DERIVED

MeSH Terms

Interventions

eplontersen

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2020
• First Posted: March 10, 2020
• Study Start: April 23, 2020
• Primary Completion: September 10, 2020
• Study Completion: September 10, 2020
• Last Updated: March 31, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)