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

NCT05337878 | Completed Phase 1 FDA Drug

• 1 other identifier: AKCEA-CS1
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (4)

• 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

Study Arms (6)

SAD: Placebo

PLACEBO COMPARATOR

Single dose of Pelacarsen-matching placebo administered by SC injection on Day 1 of single-dose treatment period.

Drug: Placebo

SAD: Pelacarsen 20 milligrams (mg)

EXPERIMENTAL

Single dose of Pelacarsen, 20 mg, administered by SC injection on Day 1 of single-dose treatment period.

Drug: Pelacarsen

SAD: Pelacarsen 40 mg

EXPERIMENTAL

Single dose of Pelacarsen, 40 mg, administered by SC injection on Day 1 of single-dose treatment period.

Drug: Pelacarsen

SAD: Pelacarsen 80 mg

EXPERIMENTAL

Single dose of Pelacarsen, 80 mg, administered by SC injection on Day 1 of single-dose treatment period.

Drug: Pelacarsen

MD: Placebo

PLACEBO COMPARATOR

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

MD: Pelacarsen 80 mg

EXPERIMENTAL

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

Interventions

Placebo DRUG

Pelacarsen-matching placebo administered by SC injection.

MD: Placebo; SAD: Placebo

Pelacarsen DRUG

Pelacarsen administered by SC injection.

Also known as: AKCEA-APO(a)-LRx, TQJ230, ISIS 681257

MD: Pelacarsen 80 mg; SAD: Pelacarsen 20 milligrams (mg); SAD: Pelacarsen 40 mg; SAD: Pelacarsen 80 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provided written informed consent (signed and dated) and any authorizations required by local law and was able to comply with all study requirements.
• Male and female of first-, second- or third-generation Japanese participants.
• 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.
• Participants weighed at least 45 kilograms (kg), healthy or obese with body mass index (BMI) ≤ 35.0 kilograms per meter square (kg/m\^2).
• Participants had to have lipoprotein(a) (Lp\[a\]) ≥ 15 nanomole per liter (nmol/L) (8 milligram per deciliter \[mg/dL\]) at screening.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (1)

Parexel International

Glendale, California, 91206, United States

Location

Related Publications (1)

• Milosavljevic MN, Stefanovic SM, Pejcic AV. Potential Novel RNA-Targeting Agents for Effective Lipoprotein(a) Lowering: A Systematic Assessment of the Evidence From Completed and Ongoing Developmental Clinical Trials. J Cardiovasc Pharmacol. 2023 Jul 1;82(1):1-12. doi: 10.1097/FJC.0000000000001429.

  PMID: 37070852 DERIVED

MeSH Terms

Interventions

pelacarsen; AKCEA-APO(a)-LRx

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2022
• First Posted: April 20, 2022
• Study Start: October 15, 2018
• Primary Completion: December 18, 2019
• Study Completion: December 18, 2019
• Last Updated: April 20, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)