A Study to Investigate the Safety of GSK4024484 in Healthy Adult Participants

NCT06171113 | Recruiting Phase 1 DMC

• 1 other identifier: 218708
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of the study is to characterise the safety of GSK4024484 in healthy participants within a controlled pharmacokinetic (PK) range, and the effect of food on the study intervention.

Conditions

Malaria, Falciparum

Keywords

First time in human; Safety; Pharmacokinetics; GSK4024484; Healthy adults; Food effect; Single oral doses; Multiple oral doses

Outcome Measures

Primary Outcomes (8)

• Percentage of participants reporting serious adverse events (SAEs) after single ascending doses

  An SAE is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or an abnormal partner pregnancy outcome.

  From the signing of the informed consent (Day -2) until the follow up contact (Day 38 +/- 3 days post dose)

• Percentage of participants reporting SAEs by severity after single ascending doses

  Mild SAE = a type of adverse event (AE) that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate SAE = a type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe SAE = a type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.

  From the signing of the informed consent (Day -2) until the follow up contact (Day 38 +/- 3 days post dose)

• Percentage of participants reporting SAEs after multiple ascending doses

  An SAE is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or an abnormal partner pregnancy outcome.

  From the signing of the informed consent (Day -2) until the follow up contact (Day 40 +/- 3 days post dose)

• Percentage of participants reporting SAEs by severity after multiple ascending doses

  Mild SAE = a type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate SAE = a type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe SAE = a type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.

  From the signing of the informed consent (Day -2) until the follow up contact (Day 40 +/- 3 days post dose)

• Percentage of participants reporting non-serious AEs after single ascending doses

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.

  From study dose administration (Day 1) until the follow up contact (Day 38 +/- 3 days post dose)

• Percentage of participants reporting non-serious AEs by severity after single ascending doses

  Mild AE = a type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate AE = a type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe AE = a type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.

  From study dose administration (Day 1) until the follow up contact (Day 38 +/- 3 days post dose)

• Percentage of participants reporting non-serious AEs after multiple ascending doses

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.

  From first study dose administration (Day 1) until the follow up contact (Day 40 +/- 3 days post dose)

• Percentage of participants reporting non-serious AEs by severity after multiple ascending doses

  Mild AE = a type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate AE = a type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe AE = a type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.

  From first study dose administration (Day 1) until the follow up contact (Day 40 +/- 3 days post dose)

Secondary Outcomes (19)

• Part A: Area under the plasma drug concentration versus time curve from time zero (pre-dose) to last time of quantifiable concentration [AUC(0-t)] of GSK4024484C following single ascending doses in fasting conditions

  From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)

• Part A: Area under the plasma drug concentration versus time curve from zero (pre-dose) extrapolated to infinite time [AUC(0-∞)] of GSK4024484C following single ascending doses in fasting conditions

  From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)

• Part A: Maximum observed plasma drug concentration (Cmax) of GSK4024484C following single ascending doses in fasting conditions

  From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)

• Part A: Time to maximum observed plasma drug concentration (Tmax) of GSK4024484C following single ascending doses in fasting conditions

  From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)

• Part A: Apparent terminal half-life (t1/2) of GSK4024484C following single ascending doses in fasting conditions

  From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)

Study Arms (15)

6 mg single ascending dose (SAD) Group

EXPERIMENTAL

Participants receive a 6 mg single dose of GSK4024484, in a fasted state.

Drug: GSK4024484C

12 mg SAD Group

EXPERIMENTAL

Participants receive a 12 mg single dose of GSK4024484 in a fasted state.

Drug: GSK4024484C

24 mg SAD Group

EXPERIMENTAL

Participants receive a 24 mg single dose of GSK4024484 in a fasted state.

Drug: GSK4024484C

48 mg SAD Group

EXPERIMENTAL

Participants receive a 48 mg single dose of GSK4024484 in a fasted state.

Drug: GSK4024484C

96 mg SAD Group

EXPERIMENTAL

Participants receive a 96 mg single dose of GSK4024484 in a fasted state.

Drug: GSK4024484C

192 mg SAD Group

EXPERIMENTAL

Participants receive a 192 mg single dose of GSK4024484, in a fasted state.

Drug: GSK4024484C

Food Effect Group

EXPERIMENTAL

Participants receive a single study dose of GSK4024484 in a fed state.

Drug: GSK4024484C

300 mg SAD Group

EXPERIMENTAL

Participants receive a 300 mg single dose of GSK4024484, in a fasted state.

Drug: GSK4024484C

400 mg SAD Group

EXPERIMENTAL

Participants receive a 400 mg single dose of GSK4024484, in a fasted state.

Drug: GSK4024484C

Optional SAD Group

EXPERIMENTAL

Participants may be included in this group, to allow flexibility if the dose escalation needs modification or a dose level needs to be added or repeated.

Drug: GSK4024484C

Placebo SAD Group

PLACEBO COMPARATOR

Participants receive placebo in a fed or fasted state.

Drug: Placebo

150 mg multiple ascending doses (MAD) Group

EXPERIMENTAL

Participants receive 150 mg per day of GSK4024484 during 3 subsequent days (450 mg total).

Drug: GSK4024484C

300 mg MAD Group

EXPERIMENTAL

Participants receive 300 mg per day of GSK4024484 during 3 subsequent days (900 mg total).

Drug: GSK4024484C

Optional MAD Group

EXPERIMENTAL

Participants may be included in this group, to allow flexibility if the dose escalation needs modification or a dose level needs to be added or repeated.

Drug: GSK4024484C

Placebo MAD Group

PLACEBO COMPARATOR

Participants receive placebo during 3 subsequent days.

Drug: Placebo

Interventions

GSK4024484C DRUG

Doses administrated orally with 240 mL of water.

12 mg SAD Group; 150 mg multiple ascending doses (MAD) Group; 192 mg SAD Group; 24 mg SAD Group; 300 mg MAD Group; 300 mg SAD Group; 400 mg SAD Group; 48 mg SAD Group; 6 mg single ascending dose (SAD) Group; 96 mg SAD Group; Food Effect Group; Optional MAD Group; Optional SAD Group

Placebo DRUG

Doses administrated orally with 240 mL of water.

Placebo MAD Group; Placebo SAD Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must be 18 to 60 years of age inclusive, at the time of signing the informed consent.
• Participants who are considered healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac assessment.

You may not qualify if:

• ALT (Alanine transaminase) and AST (Aspartate transaminase) within the normal range at screening.
• Total bilirubin within the normal range unless the participant is known to have Gilbert's syndrome.
• Body weight ≥50kg, and BMI within the range 19 to 32 kilogram per square metre (kg/m\^2) inclusive.
• Male participants and female participants who are not of child bearing potential.
• The participant is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
• History or presence of cardiovascular (including hypertension), respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurological disorders, capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data in the opinion of the investigator.
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• An average weekly alcohol intake of \>14 units a week within 6 months prior to the study. One unit is equivalent to 8 g of alcohol: a half-pint (\~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
• QTcF (Fridericia's formula) \>450 msec based on average of triplicate ECGs. The QTcF is the QT interval corrected for heart rate according to QTcF.
• More than 100 ventricular ectopic complexes in 24 hrs by Holter screening or any other clinically significant Holter abnormalities determined by the investigator.
• Presence or history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
• Heart rate \<40 or \>100 beats per minute (bpm).
• Evidence of previous myocardial infarction or any clinically significant conduction abnormality such as (including but not specific to left complete bundle branch block, AV block \[2nd degree or higher\], WPW syndrome). Long standing RBBB is permitted.
• Past or intended use of over-the-counter or prescription medication, including herbal medications, CBD-based products, PPIs or H2 antagonists within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is the longest) prior to dosing. Other concomitant medication may be considered on a case by case basis by the investigator in consultation with the medical monitor. Paracetamol is permitted (capped at ≤2 grams/day).
• Participation in the study that would result in loss of blood or blood products in excess of 500 mL within a 56-day period.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 0GG, United Kingdom

RECRUITING

MeSH Terms

Conditions

Malaria, Falciparum

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

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: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2023
• First Posted: December 14, 2023
• Study Start: December 11, 2023
• Primary Completion (Estimated): August 7, 2026
• Study Completion (Estimated): August 7, 2026
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

GB (1)