A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics (PD) of GSK3888130B in Healthy Participants

Multiple Sclerosis Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo Controlled, Single Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK3888130B in Healthy Participants Aged 18-55 Inclusive

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05131971
• Other study ID #: 213960
• Secondary ID: 2021-002063-22
• Status: Completed
• Phase: Phase 1
• Start date: November 1, 2021
• Est. completion date: October 12, 2023

Study information

• Verified date: March 2024
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: October 12, 2023
• Est. primary completion date: October 12, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

• Additional inclusion criteria for Immune Challenge Model Cohorts: Participants with a history of Bacillus Calmette Guerin (BCG) vaccination as evidenced by a BCG scar or documented medical history of a BCG vaccination with/without a BCG scar. Verbal communication of BCG vaccination from the participant will be acceptable if documentation is not available or a BCG scar is not visible and recorded in the source notes.

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.

• Additional exclusion criteria for Immune Challenge Model Cohorts: History of a severe local reaction to tuberculin products.

• 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, within 7 days of dosing, in recreational sun-bathing, or use of sunbed, on the area of the skin from wrist to shoulder inclusive.

• Current smoker or user of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) during or within 30 days prior to study participation.

• An average weekly intake of >14 units of alcohol.

Related Conditions & MeSH terms

• Multiple Sclerosis

Intervention

Drug:
• GSK3888130B
GSK3888130B will be administered.
• Placebo
Placebo will be administered.

Locations

Country	Name	City	State
United Kingdom	GSK Investigational Site	Cambridge

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events (AEs) and serious adverse events (SAEs)		Up to 110 days
Primary	Number of participants with clinically significant changes in laboratory parameters, vital signs and 12-lead electrocardiogram (ECG) findings		Up to 85 days
Secondary	Serum concentrations of GSK3888130B		Up to 85 days
Secondary	Area under the concentration-time curve from time zero to time t (AUC[0 to t]) of GSK3888130B		Up to 85 days
Secondary	Maximum concentration (Cmax) of GSK3888130B in serum		Up to 85 days
Secondary	Time to Cmax (Tmax) of GSK3888130B		Up to 85 days
Secondary	Half-life (t1/2) of GSK3888130B		Up to 85 days
Secondary	Clearance (CL) of GSK3888130B		Up to 85 days
Secondary	Number of participants with positive anti-drug antibodies against GSK3888130B		Up to 85 days
Secondary	Change from Baseline in derived free Interleukin-7 (IL-7) protein levels over time		Baseline (Day 1) and up to 85 days
Secondary	Change in PD biomarker: T cell B-cell lymphoma 2 (Bcl-2) measured in blood over time		Baseline (Day 1) and up to 85 days