First-in-Human Dose-escalation of GSK4425689A: Safety, Tolerability, and PK in Healthy Adults

NCT07646353 | Not Yet Recruiting Phase 1

• 1 other identifier: 223290
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will assess the safety, tolerability, and pharmacokinetic properties of GSK4425689A monoclonal antibody (mAb) in healthy adults, when administered by either intravenous (IV) or subcutaneous (SC) routes.

Conditions

Malaria, Falciparum

Keywords

Malaria; GSK4425689A; First-in-human; Safety; Tolerability; Pharmacokinetic; Healthy Adults; Dose escalation; Monoclonal antibody (mAb)

Outcome Measures

Primary Outcomes (2)

• Number of participants with adverse events (AEs) overall and by severity

  An AE is defined as 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. Grades are defined based on numeric criteria as follows Grade 1: mild; Grade 2: moderate; Grade 3: severe. Higher grades indicate greater severity.

  From Day 1 up to Day 364

• Number of participants with serious adverse events (SAEs) overall and by severity

  An SAE is defined as any untoward medical . occurrence that results in death, is life- . threatening, requires inpatient hospitalization or extends existing hospitalization, causes . persistent or significant disability/incapacity, involves a congenital anomaly/birth defect in a participants offspring, includes an abnormal . pregnancy outcome, or occurs in any other . situation per the investigators judgement. Grades are defined based on numeric criteria as follows Grade 1: mild; Grade 2: moderate; Grade 3: severe. Higher grades indicate greater severity.

  From Day -28 [informed consent form (ICF) signing] up to Day 364

Secondary Outcomes (13)

• Bioavailability (F) of SC administration

  From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour (h)) and at approximately 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose

• Terminal serum half-life (t1/2)

  From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approximately 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose

• Clearance (CL) of IV administration and apparent clearance (CL/F) of SC administration

  From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approximately 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose

• Volume of distribution (Vd) of IV administration and apparent volume of distribution (Vd/F) of SC administration

  From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approximately 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose

• Maximum observed serum concentration (Cmax)

  From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approximately 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose

Study Arms (5)

GSK4425689A Low Dose SC Group

EXPERIMENTAL

Participants receive a low dose of GSK4425689A subcutaneously (SC) on Day 1.

Biological: GSK4425689A SC; Drug: Placebo

GSK4425689A Low Dose IV Group

EXPERIMENTAL

Participants receive a low dose of GSK4425689A intravenously (IV) on Day 1.

Biological: GSK4425689A IV; Drug: Placebo

GSK4425689A Medium Dose SC Group

EXPERIMENTAL

Participants receive a medium dose of GSK4425689A SC on Day 1.

Biological: GSK4425689A SC; Drug: Placebo

GSK4425689A Medium Dose IV Group

EXPERIMENTAL

Participants receive a medium dose of GSK4425689A IV on Day 1.

Biological: GSK4425689A IV; Drug: Placebo

GSK4425689A High Dose IV Group

EXPERIMENTAL

Participants receive a high dose of GSK4425689A IV on Day 1.

Biological: GSK4425689A IV; Drug: Placebo

Interventions

GSK4425689A SC BIOLOGICAL

Participants receive GSK4425689A SC.

GSK4425689A Low Dose SC Group; GSK4425689A Medium Dose SC Group

GSK4425689A IV BIOLOGICAL

Participants receive GSK4425689A IV.

GSK4425689A High Dose IV Group; GSK4425689A Low Dose IV Group; GSK4425689A Medium Dose IV Group

Placebo DRUG

Participants receive Placebo in the same volume and route as the participants receiving GSK4425689A in the same cohort.

GSK4425689A High Dose IV Group; GSK4425689A Low Dose IV Group; GSK4425689A Low Dose SC Group; GSK4425689A Medium Dose IV Group; GSK4425689A Medium Dose SC Group

Eligibility Criteria

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

You may qualify if:

• Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
• Participants must have a body weight between 50 and 100 kg, inclusive and body-mass index (BMI) within the range of 18.0 to 32.0 kg/m\^2.
• Participants must be healthy male or female participant of non-childbearing potential (PONCBP).
• Participants must be capable of giving signed informed consent prior to any study-specific procedures, which include compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Participants must demonstrate the ability to understand and comply with the study requirements, including attendance for all scheduled visits and adherence to protocol-specified procedures and restrictions. Participants must be willing to remain in close contact with study personnel and reliably record data as instructed.
• Participants must be in good general health and have no significant ongoing medical conditions, as determined by comprehensive medical history, thorough physical examination, vital signs assessment, 12-lead ECG, and clinical laboratory evaluations (including hematology, biochemistry, and urinalysis).

You may not qualify if:

• Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels must be within the normal range at Screening.
• Participants with a history of malaria infection or who have previously participated in malaria vaccine trials or studies involving experimental anti-malarial monoclonals, small molecule drugs, or experimental malaria challenge are excluded. Participants who have been vaccinated against malaria with an investigational or approved vaccine (e.g., RTS,S and R21/Matrix-M) are excluded.
• History of allergy to humanized monoclonal antibodies (mAbs) or constituents of the formulation.
• Any history of anaphylaxis or other severe allergic reactions, or food, or drug allergy that may impact participant safety in the opinion of the investigator.
• Recent history of, or presence of a current or suspected chronic disease that may impact participant safety, or impact interpretation of clinical study results. This includes illnesses such as (but not limited to) cardiac disease, autoimmune disease, diabetes, progressive neurological disease, severe malnutrition, hepatic or renal disease, epilepsy, chronic obstructive pulmonary disease or asthma (except resolved childhood asthma, which is acceptable). Conditions that in the opinion of the investigator constitute a risk to the individual when taking the study intervention or likely to interfere with the interpretation of data.
• Have a history of malignant neoplasm (other than localized basal or squamous cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within 5 years of Screening, regardless of whether there is evidence of local recurrence or metastases.
• Current enrolment or participation in another clinical study.
• Participation in another clinical study involving any investigational product within the past 90 days or within a period equivalent to 5 half-lives of the investigational drug, whichever is longer, or receipt of experimental non-malaria vaccines or mAbs within the past 12 months prior to signing the informed consent.
• QT corrected for heart rate by Fridericia's formula (QTcF) \>450 msec.
• Presence or history of cardiac arrhythmias or cardiac disease or a family or personal history of long-QT syndrome.
• Average heart rate of \<40 or \>100 beats per minute (bpm).
• Evidence of previous myocardial infarction or any clinically significant conduction abnormality such as left bundle branch block, atrioventricular (AV) block (2nd degree or higher), Wolff-Parkinson-White syndrome, atrial fibrillation, and atrial flutter. A long-standing right bundle branch block is permitted.
• Participants cannot take investigational product with biologic agents (such as mAbs including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to signing the informed consent.
• Past or intended use of over the counter or prescription medication, including herbal medications or cannabidiol (CBD)-based products within 14 days prior to administration of study intervention.
• Recent infection or illness:

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Condition Hierarchy (Ancestors)

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
• Masking Details: This is a double-blind study.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2026
• First Posted: June 12, 2026
• Study Start: June 12, 2026
• Primary Completion (Estimated): April 19, 2028
• Study Completion (Estimated): April 19, 2028
• Last Updated: June 12, 2026

Record last verified: 2026-06

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 asset(s) with development terminated 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.