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

Healthy Participants Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05337878
• Other study ID #: AKCEA-CS1
• Status: Completed
• Phase: Phase 1
• Start date: October 15, 2018
• Est. completion date: December 18, 2019

Study information

• Verified date: April 2022
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: December 18, 2019
• Est. primary completion date: December 18, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• Placebo
Pelacarsen-matching placebo administered by SC injection.
• Pelacarsen
Pelacarsen administered by SC injection.

Locations

Country	Name	City	State
United States	Parexel International	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SAD: Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Evaluation Parameters		Up to Day 90
Primary	SAD: Percentage of Participants With Adverse Events		Up to Day 90
Primary	SAD: Percentage of Participants With Serious Adverse Events		Up to Day 90
Primary	MAD: Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Evaluation Parameters		Up to Day 204
Primary	MAD: Percentage of Participants With Adverse Events		Up to Day 204
Primary	MAD: Percentage of Participants With Serious Adverse Events		Up to Day 204
Secondary	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
Secondary	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
Secondary	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
Secondary	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