Malaria, Falciparum
Conditions
Keywords
Malaria, GSK4425689A, First-in-human, Safety, Tolerability, Pharmacokinetic, Healthy Adults, Dose escalation, Monoclonal antibody (mAb)
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.
Interventions
BIOLOGICALGSK4425689A SC
Participants receive GSK4425689A SC.
BIOLOGICALGSK4425689A IV
Participants receive GSK4425689A IV.
DRUGPlacebo
Participants receive Placebo in the same volume and route as the participants receiving GSK4425689A in the same cohort.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a double-blind study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs) overall and by severity | From Day 1 up to Day 364 | 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. |
| Number of participants with serious adverse events (SAEs) overall and by severity | From Day -28 [informed consent form (ICF) signing] up to Day 364 | 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. |
Secondary
| 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 |
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
Outcome results
None listed