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

Sponsor

Ionis Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT04302064

Collaborator

(none)

Enrollment

Location

Arms

4.6

Actual Duration (Months)

5.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Healthy Participants	Drug: Eplontersen Drug: Placebo	Phase 1

Detailed Description

This is a single-center, double-blinded, placebo-controlled study in up to 44 participants. Participants will be randomized to receive three subcutaneous single-ascending doses and potentially multiple doses of Eplontersen or placebo.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blinded, Placebo-Controlled, Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending and Multiple Doses of ION-682884 in Healthy Japanese Participants

Actual Study Start Date :

Apr 23, 2020

Actual Primary Completion Date :

Sep 10, 2020

Actual Study Completion Date :

Sep 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eplontersen Single dose on Day 1 or multiple doses (every 4 weeks for 12 weeks) of Eplontersen administered SC.	Drug: Eplontersen Eplontersen administered SC Other Names: ION-682884 AKCEA-TTR-LRx IONIS-TTR-LRx
Placebo Comparator: Placebo Single dose on Day 1 or multiple doses (every 4 weeks for 12 weeks) of Eplontersen-matching placebo administered SC.	Drug: Placebo Eplontersen-matching placebo administered SC

Arm

Intervention/Treatment

Experimental: Eplontersen

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

Drug: Eplontersen

Eplontersen administered SC

Other Names:

ION-682884

AKCEA-TTR-LRx

IONIS-TTR-LRx

Placebo Comparator: Placebo

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

Drug: Placebo

Eplontersen-matching placebo administered SC

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria

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

Exclusion Criteria

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
Screening laboratory results as follows, or any other clinically significant abnormalities in Screening laboratory values that would render a participant unsuitable for inclusion

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	WCCT Global	Cypress	California	United States	90630

Sponsors and Collaborators

Ionis Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ionis Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT04302064

Other Study ID Numbers:

ION-682884-CS20

First Posted:

Mar 10, 2020

Last Update Posted:

Mar 31, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Study Results

No Results Posted as of Mar 31, 2022