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

A First-in-Human Dose-escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GSK4425689A in Healthy Adult Participants

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Malaria, Falciparum
• Intervention / Treatment: Biological: GSK4425689A SC; Drug: Placebo; Biological: GSK4425689A IV

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
2. 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.
3. Participants must be healthy male or female participant of non-childbearing potential (PONCBP).
4. 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.
5. 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.
6. 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).
7. Participants should have baseline (screening) clinical laboratory values (renal, hepatic, and hematological) within normal limits or clinically acceptable to the investigator. A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, or outside the normal reference range for the population being studied, may be included only if the investigator considers that the finding is unlikely to introduce additional risk factors for the participant and will not interfere with the study procedures or endpoints.
8. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels must be within the normal range at Screening.

Exclusion Criteria:

1. 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.
2. History of allergy to humanized monoclonal antibodies (mAbs) or constituents of the formulation.
3. 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.
4. 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.
5. 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.
6. Current enrolment or participation in another clinical study.
7. 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.
8. QT corrected for heart rate by Fridericia's formula (QTcF) >450 msec.
9. Presence or history of cardiac arrhythmias or cardiac disease or a family or personal history of long-QT syndrome.
10. Average heart rate of <40 or >100 beats per minute (bpm).
11. 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.
12. 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.
13. 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.

14. Recent infection or illness:

    • Participants with any acute illness or infection requiring treatment within 28 days prior to Screening are excluded (but may be re-screened if appropriate).
    • Participants with evidence of active infections, such as Coronavirus disease 2019 (COVID-19) or tuberculosis are excluded.
15. Participants who have received any live vaccines within 3 months prior to Screening or plan to receive such vaccines during the clinical study.
16. Positive drug screen at Screening, including tetrahydrocannabinol, indicating use of known recreational drugs or drugs of abuse.
17. An average weekly alcohol intake of >21 units per week for male participants and >14 units per week for female participants within 6 months prior to Screening. 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.
18. Any individual who is a current smoker or has a history of cigarette smoking of more than 5 pack years or regular use of tobacco- or nicotine-containing products within 6 months prior to Screening (including e-cigarettes or vaping).

19. Pregnancy and lactation:

    • Participants of childbearing potential (POCBP) are excluded.
    • Pregnant or breastfeeding females are excluded.
20. Participants who have donated 500 mL or more of blood or blood products within 12 weeks before administration of study intervention are excluded.

21. Concomitant conditions:

    • Positive human immunodeficiency virus (HIV) antibody test.
22. Current or chronic history of liver disease or known hepatic or biliary abnormalities (except for clinically established Gilbert's syndrome or asymptomatic gallstones).
23. Presence of hepatitis B surface antigen (HBsAg) at Screening or within 3 months prior to first dose of study intervention.
24. Positive hepatitis C antibody test result at Screening or within 3 months prior to first dose of study intervention.
25. Positive hepatitis C RNA test result at Screening or within 3 months prior to first dose of study intervention.
26. History of severe reactions to IV or SC injections (e.g., anaphylaxis, vasovagal syncope).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK4425689A Low Dose SC Group; Participants receive a low dose of GSK4425689A subcutaneously (SC) on Day 1.	Biological: GSK4425689A SC; Participants receive GSK4425689A SC.; Drug: Placebo; Participants receive Placebo in the same volume and route as the participants receiving GSK4425689A in the same cohort.
Experimental: GSK4425689A Low Dose IV Group; Participants receive a low dose of GSK4425689A intravenously (IV) on Day 1.	Drug: Placebo; Participants receive Placebo in the same volume and route as the participants receiving GSK4425689A in the same cohort.; Biological: GSK4425689A IV; Participants receive GSK4425689A IV.
Experimental: GSK4425689A Medium Dose SC Group; Participants receive a medium dose of GSK4425689A SC on Day 1.	Biological: GSK4425689A SC; Participants receive GSK4425689A SC.; Drug: Placebo; Participants receive Placebo in the same volume and route as the participants receiving GSK4425689A in the same cohort.
Experimental: GSK4425689A Medium Dose IV Group; Participants receive a medium dose of GSK4425689A IV on Day 1.	Drug: Placebo; Participants receive Placebo in the same volume and route as the participants receiving GSK4425689A in the same cohort.; Biological: GSK4425689A IV; Participants receive GSK4425689A IV.
Experimental: GSK4425689A High Dose IV Group; Participants receive a high dose of GSK4425689A IV on Day 1.	Drug: Placebo; Participants receive Placebo in the same volume and route as the participants receiving GSK4425689A in the same cohort.; Biological: GSK4425689A IV; Participants receive GSK4425689A IV.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Time to reach Cmax (Tmax)	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
Area under the serum concentration-time curve (AUC) from time zero up to 168 hours (AUC0-168)	From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approximately 4, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose
AUC0-672	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 and 672 hours post-dose
AUC from time zero up to the time of the last quantifiable sample (AUC0-t)	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
AUC extrapolated to infinity (AUC0-inf)	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
Dose proportionality of Cmax following IV administration	From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approx. 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Dose proportionality of AUC0-t following IV administration	From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approx. 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Dose proportionality of AUC0-inf following IV administration	From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approx. 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Estimated): June 12, 2026
• Primary Completion (Estimated): April 19, 2028
• Study Completion (Estimated): April 19, 2028

Study Registration Dates

• First Submitted: June 9, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Malaria; Dose escalation; Tolerability; Pharmacokinetic; First-in-human; Healthy Adults; Monoclonal antibody (mAb); GSK4425689A
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Malaria; Malaria, Falciparum
• Other Study ID Numbers: 223290

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://d3l8i7lo48obsd.cloudfront.net/gsk-patient-level-data-sharing-july2025-1-Bgwa1UthxvluYbWYTThw.pdf
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No