Phase 1
N=54
A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics (PD) of GSK3888130B in Healthy Participants
Multiple Sclerosis · Colitis, Ulcerative
Bottom Line
View on ClinicalTrials.gov: NCT05131971 ↗Enrolled (actual)
54
Serious AEs
0.0%
Results posted
Mar 2025
Primary outcome: Primary: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) — 8; 3; 2; 6 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- GSK3888130B (Drug); Placebo (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Oct 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
8; 3; 2; 6; 2; 4 | — |
| PRIMARY Number of Participants With Clinically Significant Changes in Hematology Results |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline |
4; 1; 1; 1; 1; 3 | — |
| PRIMARY Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Changes in Clinical Chemistry Results |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Changes in Vital Sign Results |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Positive Epstein-Barr Virus (EBV) DNA |
0; 1; 0; 0; 0; 1 | — |
| PRIMARY Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration |
NA; NA; NA; 363.2; 2155.9; 15901.1 | — |
| SECONDARY Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration |
NA; NA; NA; 2540.4; NA; 5287.2 | — |
| SECONDARY Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration |
NA; NA; 201271.5; 446824.2; 365002.7; 887258.7 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to Time t (AUC[0 to t]) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration |
65.81; 1837.01; 13524.34 | — |
| SECONDARY AUC(0 to t) for Dose Levels 3 and 5 Subcutaneous Administration |
3550.71; 35669.70 | — |
| SECONDARY AUC(0 to t) for Dose Levels 6 and 7 Intravenous Administration |
153885.4; 387454.3 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration |
0.9034; 4.8156; 35.6330 | — |
| SECONDARY Cmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration |
3.4609; 36.3795 | — |
| SECONDARY Cmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration |
386.4759; 907.7045 | — |
| SECONDARY Time to Cmax (Tmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration |
0.583; 0.550; 0.558 | — |
| SECONDARY Tmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration |
168.000; 143.475 | — |
| SECONDARY Tmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration |
1.083; 2.533 | — |
| SECONDARY Half-life (t1/2) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration |
123.73; 633.05; 627.11 | — |
| SECONDARY t1/2 of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration |
784.05; 749.02 | — |
| SECONDARY t1/2 of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration |
563.53; 628.91 | — |
| SECONDARY Clearance (CL) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration |
21.501; 4.240; 6.542 | — |
| SECONDARY Clearance Factor (CL/F) of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration |
9.149; 9.297 | — |
| SECONDARY CL of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration |
5.920; 6.860 | — |
| SECONDARY Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B |
0; 0; 0; 0; 1; 0 | — |
| SECONDARY Percent Peak Reduction From Baseline in Derived Free Interleukin 7 (IL 7) in Blood |
0.0; 95.8; 99.1; 90.3; 99.9; 98.6 | — |
| SECONDARY Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood |
92427.0; 64576.0; 68096.0; 92724.0; 73182.5; 93540.5 | — |
Summary
This is a first time in human study designed to assess the safety, tolerability, pharmacokinetics and PD of GSK3888130B over a range of dose levels in healthy participants.
Eligibility Criteria
Inclusion Criteria
- Participant must be 18 to 55 years of age inclusive.
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- Participants with a confirmed positive vaccination status for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines administered at least 30 days prior to dosing in the study.
- SARS-CoV-2 screening test negative as per local guidance.
- Participants with history of current/seasonal vaccination status for influenza or who consent to receive influenza vaccine at least 30 days prior to dosing, if study dosing is during influenza season (1st October to 30th April).
- Body weight greater than or equal to (>=) 50 kilograms (kg) and body mass index (BMI) within the range 19.5-32 kilograms per square meter (kg/m^2) (inclusive).
- Male and/or female of non-childbearing potential
- Capable of giving signed informed consent.
Exclusion Criteria
- Prior medical history of anaphylaxis.
- Immunodeficiency or autoimmunity assessed by medical history.
- A history of recurrent infections.
- Treatment of a chronic infection within 3 months prior to the first dose of study drug.
- Any acute infection (including upper respiratory tract infections and urinary tract infections) which has not fully resolved within four weeks of dosing
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy.
- Current or chronic history of liver disease or known hepatic or biliary abnormalities.
- Participants with a history of renal disease or renal abnormalities.
- A clinically significant abnormality in the 12-lead ECG performed at screening.
- A clinically significant abnormality in the Holter monitor performed at screening.
- History of malignancy, including malignant or non-malignant skin cancer.
- Participants with known SARS-CoV-2 positive contacts in the past 14 days.
- Prior moderate/severe SARS-CoV-2 infection requiring oxygen supplementation or admission to hospital.
- Antibiotics or antiviral therapy within 30 days of dosing.
- Receipt of live vaccination within 30 days of dosing or plan to receive live vaccination during the study.
- Use of prescription drugs or non-prescription drugs, including non-steroidal anti inflammatory drug (NSAIDs), within 7 days prior to dosing, if in the opinion of the Investigator (in consultation with the GlaxoSmithKline [GSK] Medical Monitor if required) the medication will interfere with the study procedures or compromise participant safety.
- The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day of the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than 4 new chemical entities within 12 months prior to dosing.
- A positive drug/alcohol test at screening or Day -1
- The participant is at high-risk of Mycobacterium tuberculosis (MTB) infection in the opinion of the Investigator.
- History of asthma, allergic rhinitis or atopic dermatitis defined by the need for intermittent or continuous therapy or any other significant allergies that, in the opinion of the investigator contraindicates their participation.
- History of severe adverse reaction to local anesthetic.
- Presence of keloids or history of keloids.
- Prothrombin time (PT) or activated partial thromboplastin time (aPTT) >1.5x upper limit of normal (ULN) at screening.
- History or presence of excessive bleeding or coagulation disorders that in the opinion of the Investigator poses a safety risk with regards to participation in the trial.
- Presence of tattoos, naevi or other skin abnormalities on the volar forearm Fitzpatrick skin color grades V in the opinion of the investigator, interfere with study assessments
- Participating, withi
Data sourced from ClinicalTrials.gov (NCT05131971). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.