Study to Assess the Pharmacokinetics of Pelacarsen (TQJ230) in Participants With Mild Hepatic Impairment Compared to Matched Healthy Participants

NCT05026996 | Completed Phase 1 FDA Drug

• 1 other identifier: CTQJ230A12202
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This was a Phase I, open-label, single-dose, parallel-group study in participants with mild hepatic impairment (HI) and healthy matched control participants with normal hepatic function designed to evaluate the PK of pelacarsen following a single 80 mg s.c. dose. Participants were matched by gender, age (±10 years), and body weight (±15%).

Conditions

Hepatic Impairment

Keywords

CTQJ230; Hepatic Impairment; Subcutaneous injection; single-dose

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetic parameters of pelacarsen: Cmax

  The maximum (peak) observed drug concentration in after single-dose administration (mass x volume-1). To assess the PK properties of plasma pelacarsen after a single s.c. injection in participants with mild HI (Child-Pugh classification) as compared to matched healthy participants with normal hepatic function.

  Day 1 (0 hour (pre-dose) 0.5 hour, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 12 hour), Day 2, Day 3, Day 4, Day 8, Day 30 and Day 60

• Pharmacokinetic parameters of pelacarsen: AUClast

  The area under the concentration-time curve (AUC) from time zero to the last measurable concentration sampling time (mass x time x volume-1). To assess the PK properties of plasma pelacarsen after a single s.c. injection in participants with mild HI (Child-Pugh classification) as compared to matched healthy participants with normal hepatic function.

  Day 1 (0 hour (pre-dose) 0.5 hour, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 12 hour), Day 2, Day 3, Day 4, Day 8, Day 30 and Day 60

• Pharmacokinetic parameters of pelacarsen: AUCinf

  The AUC from time zero to infinity (mass x time x volume-1). To assess the PK properties of plasma pelacarsen after a single s.c. injection in participants with mild HI (Child-Pugh classification) as compared to matched healthy participants with normal hepatic function.

  Day 1 (0 hour (pre-dose) 0.5 hour, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 12 hour), Day 2, Day 3, Day 4, Day 8, Day 30 and Day 60

Study Arms (2)

Mild hepatic impairment patients

EXPERIMENTAL

Participants with mild hepatic impairment

Drug: Pelacarsen

Healthy participants

EXPERIMENTAL

Matched healthy participants with normal hepatic function

Drug: Pelacarsen

Interventions

Pelacarsen DRUG

Single subcutaneous injection of pelacarsen

Also known as: TQJ230

Healthy participants; Mild hepatic impairment patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants
• Signed informed consent must be obtained prior to participation in the study.
• Male and non-child bearing potential female participants, 18 to 75 years of age (inclusive), at Screening.
• Participants must weigh at least 50 kg to participate in the study, and must have a BMI within the range of 18.0 - 38.0 kg/m2, at Screening.
• Ability to communicate well with the investigator, to understand and comply with the requirements of the study.
• Must be a non-smoker or agree to smoke no more than 5 cigarettes (or equivalent) per day from Screening until Study Completion.
• Participants with mild HI (Group 2)
• Participants must have a prior diagnosis of liver cirrhosis and mild HI as defined by the Child Pugh classification with a score of 5-6, inclusive (Class A)
• Participants have been clinically stable and had no worsening of more than 1 point in Child Pugh score within 1 month prior to dosing of study treatment.
• Seated vital signs must be within the following ranges at Screening and Baseline:
• Body temperature between 35.0 to 37.5°C, inclusive;
• Systolic blood pressure between 100 to 159 mmHg, inclusive;
• Diastolic blood pressure between 60 to 109 mmHg, inclusive;
• Pulse rate between 45 - 99 bpm, inclusive.
• Participants with other stable medical disorders such as controlled diabetes, hyperlipidemia, hypothyroidism, etc., may be eligible as long as they are considered appropriate for enrollment as determined by the investigator by medical history, physical examination, ECG, and clinical laboratory tests at Screening.

You may not qualify if:

• All participants
• Use of other investigational drugs within 5 half-lives or 30 days prior to dosing of study treatment, whichever is longer.
• History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes.
• Treatment with any oligonucleotide (with an exception for COVID 19 vaccines) or SiRNA within 9 months prior to Screening.
• Participants who received any COVID 19 vaccination and/or have not completed their full COVID-19 vaccination regimen within 14 days prior to Screening.
• Women of child bearing potential, defined as all women physiologically capable of becoming pregnant. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least 6 weeks prior to the first dosing. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of child bearing potential.
• Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 16 weeks after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above.
• Known history of, or current clinically significant arrhythmias, history of prolonged QT interval corrected by Fridericia's formula (QTcF), QTcF \> 450 msec (males), or QTcF \> 460 msec (females) at Screening.
• History of immunodeficiency diseases or have a positive HIV test result at Screening.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years of Screening, regardless of whether there is evidence of local recurrence or metastases.
• Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing of study treatment.
• Platelet count ≤ LLN at Screening or Baseline.
• History of unhealthy alcohol use within 12 months prior to dosing of study treatment, as defined by a recurring pattern of either binge drinking (≥ 5 drinks over 2 3 hours on ≥ 5 days/month) or heavy drinking (≥ 8 drinks/week in females or \> 15 drinks/week in males). A "drink" definition includes: 12 ounces of 5% beer, 8 ounces of 7% malt liquor, 5 ounces of 12% wine or 1.5 ounces of 40% spirits.
• Positive alcohol screen at Screening or Baseline.
• History of drug abuse within the last 12 months or evidence of such abuse as indicated by the laboratory assay conducted during Screening or Baseline, unless the positive drug screen is due to prescription drug use that is approved by the investigator and Novartis.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

San Antonio, Texas, 78215, 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

Related Links

• Results for CTQJ230A12202 that is getting linked from the Novartis Clinical Trials Website
• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Interventions

pelacarsen

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This was a Phase I, open-label, single dose, parallel-group study in participants with mild HI (n=8) and matched healthy participants with normal hepatic function (n=8) designed to evaluate the PK of pelacarsen. Participants were matched by gender, age (± 10 years), and body weight (± 15%).

Study Record Dates

• First Submitted: August 4, 2021
• First Posted: August 30, 2021
• Study Start: November 23, 2021
• Primary Completion: October 19, 2022
• Study Completion: October 19, 2022
• Last Updated: October 9, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)