A Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Pelacarsen (ISIS 681257) in Healthy Japanese Participants

A Randomized Double-blind, Placebo-controlled, Non-confirmatory Study to Assess Safety, Tolerability, PK, and PD of Single Ascending and Multiple Doses of ISIS 681257 in Healthy Japanese Participants

The purpose of the study is to assess the safety, tolerability, and pharmacokinetics (PK) of single and multiple subcutaneous (SC) doses of Pelacarsen (ISIS 681257) in healthy Japanese participants.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Placebo; Drug: Pelacarsen

Detailed Description

This was a randomized, placebo-controlled, participant and investigator-blinded, single ascending and multiple-dose study of Pelacrsen (ISIS 681257) in up to 29 healthy Japanese male and female participants. The study was conducted in two parts:1) Single ascending dose (SAD) including up to a 28-day screening period, a baseline period, dose with study drug on Day 1, a 2-day (48 hours) post-dose in-patient observation period, followed by an out-patient observation period up to Day 90; 2) Multiple doses (MD) including up to a 28-day screening period, a baseline period, dose with study drug up to Day 85, a 2-day (48 hours) post-dose in-patient observation period, followed by an out-patient observation period up to Day 204.

In the SAD period, participants were randomized to receive single dose of Pelacarsen or placebo.

Upon completion of the SAD period participants were randomized to receive multiple doses of Pelacarsen.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Parexel International

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provided written informed consent (signed and dated) and any authorizations required by local law and was able to comply with all study requirements.
2. Male and female of first-, second- or third-generation Japanese participants.
3. Japanese healthy or obese male and female participants 18 to 65 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, ECG and laboratory tests at screening.
4. Participants weighed at least 45 kilograms (kg), healthy or obese with body mass index (BMI) ≤ 35.0 kilograms per meter square (kg/m^2).
5. Participants had to have lipoprotein(a) (Lp[a]) ≥ 15 nanomole per liter (nmol/L) (8 milligram per deciliter [mg/dL]) at screening.

Exclusion Criteria:

1. Clinically significant abnormalities in medical history including acute coronary syndrome, major surgery within 3 months of screening, planned surgery that would have occurred during the study or physical examination or other screening results such as ECGs findings at screening.

Screening laboratory results as follows or any other clinically significant abnormalities in screening laboratory values that would have rendered a participant unsuitable for inclusion. If abnormal, the laboratory tests may have been repeated after consultation with the Sponsor Medical Monitor.

• Estimated glomerular filtration rate (eGFR) ˂ 60 milliliter per minute per 1.73 meter per square (mL/min/1.73m^2) (as determined by the Chronic Kidney Disease-Epidemiological Collaboration [CKD-EPI] Equation).
• Urine protein-to-creatinine ratio (UPCR) ≥ 200 milligram per gram (mg/g) or urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g.
• Alanine aminotransferase (ALT; serum glutamic pyruvic transaminase), aspartate aminotransferase (AST; serum glutamic oxaloacetic transaminase), bilirubin, alkaline phosphatase, serum creatinine, blood urea nitrogen > 1.5 × upper limit of normal (ULN) at screening excluded a participant from participation in the study.
• Fasting blood glucose > ULN. If elevated, hemoglobin A1c was checked and if < 6%, the participant could have been enrolled.
• Platelet count < 140,000 per microliter (/μL). 3. Active infection requiring systemic antiviral or antimicrobial therapy that would not have been completed prior to Day 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: SAD: Placebo; Single dose of Pelacarsen-matching placebo administered by SC injection on Day 1 of single-dose treatment period.	Drug: Placebo; Pelacarsen-matching placebo administered by SC injection.
EXPERIMENTAL: SAD: Pelacarsen 20 milligrams (mg); Single dose of Pelacarsen, 20 mg, administered by SC injection on Day 1 of single-dose treatment period.	Drug: Pelacarsen; Pelacarsen administered by SC injection.; Other Names: TQJ230; AKCEA-APO(a)-LRx; ISIS 681257
EXPERIMENTAL: SAD: Pelacarsen 40 mg; Single dose of Pelacarsen, 40 mg, administered by SC injection on Day 1 of single-dose treatment period.	Drug: Pelacarsen; Pelacarsen administered by SC injection.; Other Names: TQJ230; AKCEA-APO(a)-LRx; ISIS 681257
EXPERIMENTAL: SAD: Pelacarsen 80 mg; Single dose of Pelacarsen, 80 mg, administered by SC injection on Day 1 of single-dose treatment period.	Drug: Pelacarsen; Pelacarsen administered by SC injection.; Other Names: TQJ230; AKCEA-APO(a)-LRx; ISIS 681257
PLACEBO_COMPARATOR: MD: Placebo; Multiple doses of Pelacarsen-matching placebo administered by SC injection every 4 weeks, on Days 1, 29, 57 and 85 of multiple-dose treatment period.	Drug: Placebo; Pelacarsen-matching placebo administered by SC injection.
EXPERIMENTAL: MD: Pelacarsen 80 mg; Multiple doses of Pelacarsen, 80 mg, administered by SC injection every 4 weeks, on Days 1, 29, 57 and 85 of multiple-dose treatment period.	Drug: Pelacarsen; Pelacarsen administered by SC injection.; Other Names: TQJ230; AKCEA-APO(a)-LRx; ISIS 681257

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
SAD: Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Evaluation Parameters	Up to Day 90
SAD: Percentage of Participants With Adverse Events	Up to Day 90
SAD: Percentage of Participants With Serious Adverse Events	Up to Day 90
MAD: Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Evaluation Parameters	Up to Day 204
MAD: Percentage of Participants With Adverse Events	Up to Day 204
MAD: Percentage of Participants With Serious Adverse Events	Up to Day 204

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Drug Concentration (Cmax) in Plasma After Single Ascending Dose of Pelacarsen	Day 1: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 up to 168 hours post-dose
Area Under Curve (AUC) From Time Zero to the Last Quantifiable Concentration (AUClast) in Plasma After Single Ascending Dose of Pelacarsen	Day 1: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 up to 168 hours post-dose
Maximum Observed Drug Concentration (Cmax) in Plasma After Multiple Doses of Pelacarsen	Days 1 and 85: Pre-dose; 1, 2, 4, 8, 24 up to 168 hours post-dose
Area Under Curve (AUC) From Time Zero to the Last Quantifiable Concentration (AUClast) in Plasma After Multiple Doses of Pelacarsen	Days 1 and 85: Pre-dose; 1, 2, 4, 8, 24 up to 168 hours post-dose

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 15, 2018
• Primary Completion (ACTUAL): December 18, 2019
• Study Completion (ACTUAL): December 18, 2019

Study Registration Dates

• First Submitted: April 13, 2022
• First Submitted That Met QC Criteria: April 13, 2022
• First Posted (ACTUAL): April 20, 2022

Study Record Updates

• Last Update Posted (ACTUAL): April 20, 2022
• Last Update Submitted That Met QC Criteria: April 13, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: AKCEA-CS1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No