Malaria, FalciparumPhase 1NCT07646353
First-in-Human Dose-escalation of GSK4425689A: Safety, Tolerability, and PK in Healthy Adults
A Phase 1 study testing GSK4425689A SC and GSK4425689A IV in people with Malaria, Falciparum, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria, Falciparum
- What is being tested?
- GSK4425689A SC and GSK4425689A IV
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 27 Jul 2026to 10 Apr 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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).
- 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.
- Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels must be within the normal range at Screening.
Who cannot join
- 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.
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- 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:
- 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.
- Participants who have received any live vaccines within 3 months prior to Screening or plan to receive such vaccines during the clinical study.
- Positive drug screen at Screening, including tetrahydrocannabinol, indicating use of known recreational drugs or drugs of abuse.
- 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.
- 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).
- Pregnancy and lactation:
- Participants of childbearing potential (POCBP) are excluded.
- Pregnant or breastfeeding females are excluded.
- Participants who have donated 500 mL or more of blood or blood products within 12 weeks before administration of study intervention are excluded.
- Concomitant conditions:
- Positive human immunodeficiency virus (HIV) antibody test.
- Current or chronic history of liver disease or known hepatic or biliary abnormalities (except for clinically established Gilbert's syndrome or asymptomatic gallstones).
- Presence of hepatitis B surface antigen (HBsAg) at Screening or within 3 months prior to first dose of study intervention.
- Positive hepatitis C antibody test result at Screening or within 3 months prior to first dose of study intervention.
- Positive hepatitis C RNA test result at Screening or within 3 months prior to first dose of study intervention.
- History of severe reactions to IV or SC injections (e.g., anaphylaxis, vasovagal syncope).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
GSK Investigational Site
Manchester, M23 9QZ
US GSK Clinical Trials Call Center, 877-379-3718, GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Centre, +44 (0) 20 8990 4466, GSKClinicalSupportHD@gsk.com
About this study
Official title: 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.
- Conditions
- Malaria, Falciparum
- Being tested
- GSK4425689A SC, GSK4425689A IV, Placebo
- Keywords
- Malaria, GSK4425689A, First-in-human, Safety, Tolerability, Pharmacokinetic, Healthy Adults, Dose escalation, Monoclonal antibody (mAb)
- Medical subject headings
- Malaria, Falciparum, Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK4425689A SCBiological
Participants receive GSK4425689A SC.
GSK4425689A IVBiological
Participants receive GSK4425689A IV.
PlaceboDrug
Participants receive Placebo in the same volume and route as the participants receiving GSK4425689A in the same cohort.
| Study group | Role | What they receive |
|---|---|---|
| GSK4425689A Low Dose SC Group | Experimental | Participants receive a low dose of GSK4425689A subcutaneously (SC) on Day 1. Receives: Biological: GSK4425689A SC; Drug: Placebo |
| GSK4425689A Low Dose IV Group | Experimental | Participants receive a low dose of GSK4425689A intravenously (IV) on Day 1. Receives: Biological: GSK4425689A IV; Drug: Placebo |
| GSK4425689A Medium Dose SC Group | Experimental | Participants receive a medium dose of GSK4425689A SC on Day 1. Receives: Biological: GSK4425689A SC; Drug: Placebo |
| GSK4425689A Medium Dose IV Group | Experimental | Participants receive a medium dose of GSK4425689A IV on Day 1. Receives: Biological: GSK4425689A IV; Drug: Placebo |
| GSK4425689A High Dose IV Group | Experimental | Participants receive a high dose of GSK4425689A IV on Day 1. Receives: Biological: GSK4425689A IV; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: From Day -28 [informed consent form (ICF) signing] up to Day 364
Secondary outcomes (13)
Bioavailability (F) of SC administration
Measured: From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour) 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)
Measured: From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour) 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
Measured: From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour) 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
Measured: From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour) 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)
Measured: From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour) 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)
Measured: From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour) 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)
Measured: From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour) and at approximately 4, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose
AUC0-672
Measured: From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour) 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)
Measured: From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour) 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)
Measured: From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour) 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
Measured: From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour) 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
Measured: From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour) 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
Measured: From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour) and at approx. 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2026
- Study start27 Jul 2026
- Primary completion10 Apr 2028 (estimated)
- Study completion10 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malaria, FalciparumStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07646353
- Sponsor's protocol ID
- 223290
- Status last verified
- Sep 2026
- First submitted
- 9 Jun 2026
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.pdf