GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects

NCT06274853 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 170327-00016830/0003
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to evaluate the safety, tolerability, and pharmacokinetics of GS-441524 in healthy subjects. The main questions to answer are: 1) What dosage of GS-441524 is required for adequate therapeutic plasma levels? 2) Does fed or fasted state produce variability in plasma levels? 3) How is GS-441524 eliminated from the body. Participants will receive varying levels of GS-441524 or placebo to evaluate AEs and plasma levels.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (8)

• Treatment-emergent adverse events (TEAEs)

  Number of incidences

  10 days

• Blood Pressure in mm/Hg

  Changes from baseline

  10 days

• Pulse in beats/min

  Changes from baseline

  10 days

• Respiratory Rate in breaths per minute

  Changes from baseline

  10 days

• Body Temperature in degrees

  Changes from baseline

  10 days

• Electrocardiogram (ECG) as measured by PR interval

  Changes from baseline

  10 days

• Electrocardiogram (ECG) as measured by QT interval

  Changes from baseline

  10 days

• Electrocardiogram (ECG) as measured by QT corrected (Fridericia's)

  Changes from baseline

  10 days

Secondary Outcomes (16)

• Plasma PK Parameter C-Max

  10 days

• Plasma PK Parameter t-max

  10 days

• Plasma PK Parameter t-lag

  10 days

• Plasma PK Parameter AUC 0-last

  6 days

• Plasma PK Parameter AUC 0-inf

  6 days

Study Arms (11)

SAD Cohort 1

EXPERIMENTAL

A single oral dose of 100 mg GS-441524 under fasted conditions

Drug: GS-441524

SAD Placebo

PLACEBO COMPARATOR

Matching Placebo under fasted conditions

Drug: Placebo

SAD Cohort 2

EXPERIMENTAL

A single oral dose of 300 mg GS-441524

Drug: GS-441524

SAD Cohort 3

EXPERIMENTAL

A single oral dose of 600 mg GS-441524

Drug: GS-441524

SAD Cohort 4

EXPERIMENTAL

A single oral dose of 1000 mg GS-441524

Drug: GS-441524

SAD Cohort 5

EXPERIMENTAL

Optional Cohort - dose TBD

Drug: GS-441524

Food Effect

EXPERIMENTAL

Randomized, balanced, single-dose, two-treatment (fed vs fasting), two-period, two sequence crossover study part in healthy human subjects Treatment A: a single oral dose of TBD mg GS-441524 under fasted conditions Treatment B: a single oral dose of TBD mg GS-441524 under fed conditions

Drug: GS-441524

MAD Cohort 1

EXPERIMENTAL

Multiple oral doses of TBD mg GS-441524under fasted or fed conditions twice daily for 5 days (Days 1 to 5) and only a morning dose on Day 6

Drug: GS-441524

MAD Cohort 2

EXPERIMENTAL

Multiple oral doses of TBD mg GS-441524under fasted or fed conditions twice daily for 5 days (Days 1 to 5) and only a morning dose on Day 6

Drug: GS-441524

MAD Cohort 3

EXPERIMENTAL

Multiple oral doses of TBD mg GS-441524under fasted or fed conditions twice daily for 5 days (Days 1 to 5) and only a morning dose on Day 6

Drug: GS-441524

MAD Placebo

PLACEBO COMPARATOR

Matching Placebo under fasted or fed conditions

Drug: Placebo

Interventions

GS-441524 DRUG

Oral GS-441524 capsules

Also known as: (2R,3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-carbonitrile

Food Effect; MAD Cohort 1; MAD Cohort 2; MAD Cohort 3; SAD Cohort 1; SAD Cohort 2; SAD Cohort 3; SAD Cohort 4; SAD Cohort 5

Placebo DRUG

Placebo capsules

Also known as: Pregelatinized starch, colloidal silicon dioxide, magnesium stearate

MAD Placebo; SAD Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must be able to verbalize understanding of the consent form, able to provide written informed consent, and verbalize willingness to complete study procedures, be able to comply with protocol requirements, rules and regulations of study site, and be likely to complete all the study interventions.
• Must be considered a healthy male or healthy female of nonchildbearing potential.
• Women of nonchildbearing potential are considered women who:
• Do not have a uterus, or
• Are surgically sterile (for example: has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation; should be verified by medical documentation), or
• Have permanent cessation of ovarian function due to ovarian failure or surgical removal of the ovaries, or
• Are postmenopausal as defined by 12 months or more of spontaneous amenorrhea as confirmed by a follicle-stimulating hormone (FSH) level \>30 mIU/mL.
• Between 18 and 55 years of age, inclusive.
• Body mass index (BMI) within 18.0 to 32.0 kg/m2, inclusive.
• Minimum weight of at least 50.0 kg at screening.
• Male subjects who are sexually active with female partners of childbearing potential must use, with their partner, a condom plus an approved method of effective contraception from the time of screening until 90 days after the last dose of investigational medicinal product (IMP). Additionally, male subjects must agree to not donate sperm during the study and for at least 90 days from the last dose of IMP. Effective methods of contraception are:
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal)
• Progestogen-only hormonal contraception (oral, injectable/implantable, or intrauterine hormone-releasing system)
• Implantable intrauterine device
• Surgical sterilization (for example, vasectomy or bilateral tubal ligation; should be verified by medical documentation)

You may not qualify if:

• Have a medical history of clinically significant neurological, cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, or psychiatric disorder as judged by an Investigator.
• Have clinically significant abnormal biochemistry, hematology, or urinalysis results as judged by an Investigator.
• Have disorders that may interfere with drug absorption, distribution, metabolism, and excretion processes.
• Positive test results for human immunodeficiency virus (HIV)-1/HIV-2 antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody.
• Serious cardiac illness or other medical condition including, but not limited to:
• Uncontrolled arrhythmias
• History of congestive heart failure
• Corrected QT value with Fridericia's formula (QTcF) \>450 msec for males and \>470 msec for females or history of prolonged QT syndrome
• Have a blood pressure reading outside of the following range: systolic blood pressure \<86 mmHg or \>149 mmHg and diastolic blood pressure \<50 mmHg or \>94 mmHg
• History of pancreatitis and history of hepatic or biliary disease, including those with known history/diagnosis of Gilbert's syndrome. Subjects with gall bladder removal \<90 days prior to screening.
• Regular alcohol consumption in males \>21 units per week and females \>14 units per week (1 unit=12 ounces of beer, 1.5 ounces of spirit, or 5 ounces of wine) within 12 months prior to screening.
• Positive test result for alcohol and/or drugs of abuse at screening or prior to the first IMP administration.
• Current smokers and those who have smoked within 90 days prior to the first IMP administration. Current users of e cigarettes and nicotine replacement products, and those who have used these products within 90 days prior to the first IMP administration.
• Concurrent treatment or treatment with an investigational drug within 30 days prior to the first dose of IMP.
• Blood donation of approximately 500 mL within 56 days or plasma donation within 7 days of screening.

Sponsors & Collaborators

• National Center for Advancing Translational Sciences (NCATS): lead
• Leidos Biomedical Research, Inc.: collaborator
• ICON Government and Public Health Solutions, Inc: collaborator

MeSH Terms

Conditions

COVID-19

Interventions

GS-441524; stearic acid

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Philip E Sanderson, PhD

  NCATS

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 8, 2024
• First Posted: February 23, 2024
• Study Start: June 15, 2024
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: February 14, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share