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

Primary Purpose

Multiple Sclerosis

Status
Recruiting
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
GSK3888130B
Placebo
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Anti-Drug Antibodies, Double-blind, GSK3888130B, Pharmacodynamics, Pharmacokinetics, Single Dose Escalation

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • GSK Investigational SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Cohort 1: Participants receiving GSK3888130B at dose level 1

Cohort 1: Participants receiving placebo

Cohort 2: Participants receiving GSK3888130B at dose level 2

Cohort 2: Participants receiving placebo

Cohort 3: Participants receiving GSK3888130B at dose level 3

Cohort 3: Participants receiving placebo

Cohort 4: Participants receiving GSK3888130B at dose level 4

Cohort 4: Participants receiving placebo

Cohort 5: Participants receiving GSK3888130B at dose level 5

Cohort 5: Participants receiving placebo

Cohort 6: Participants receiving GSK3888130B at dose level 6

Cohort 6: Participants receiving placebo

Cohort 7: Participants receiving GSK3888130B at dose level 7

Cohort 7: Participants receiving placebo

Arm Description

Outcomes

Primary Outcome Measures

Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Number of participants with clinically significant changes in laboratory parameters, vital signs and 12-lead electrocardiogram (ECG) findings

Secondary Outcome Measures

Serum concentrations of GSK3888130B
Area under the concentration-time curve from time zero to time t (AUC[0 to t]) of GSK3888130B
Maximum concentration (Cmax) of GSK3888130B in serum
Time to Cmax (Tmax) of GSK3888130B
Half-life (t1/2) of GSK3888130B
Clearance (CL) of GSK3888130B
Number of participants with positive anti-drug antibodies against GSK3888130B
Change from Baseline in derived free Interleukin-7 (IL-7) protein levels over time
Change in PD biomarker: T cell B-cell lymphoma 2 (Bcl-2) measured in blood over time

Full Information

First Posted
October 27, 2021
Last Updated
December 22, 2022
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT05131971
Brief Title
A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics (PD) of GSK3888130B in Healthy Participants
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2021 (Actual)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
June 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Anti-Drug Antibodies, Double-blind, GSK3888130B, Pharmacodynamics, Pharmacokinetics, Single Dose Escalation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Participants will be randomized to receive either GSK3888130B or placebo in single ascending dose cohorts.
Masking
ParticipantInvestigator
Masking Description
This will be a double-blind study.
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: Participants receiving GSK3888130B at dose level 1
Arm Type
Experimental
Arm Title
Cohort 1: Participants receiving placebo
Arm Type
Placebo Comparator
Arm Title
Cohort 2: Participants receiving GSK3888130B at dose level 2
Arm Type
Experimental
Arm Title
Cohort 2: Participants receiving placebo
Arm Type
Placebo Comparator
Arm Title
Cohort 3: Participants receiving GSK3888130B at dose level 3
Arm Type
Experimental
Arm Title
Cohort 3: Participants receiving placebo
Arm Type
Placebo Comparator
Arm Title
Cohort 4: Participants receiving GSK3888130B at dose level 4
Arm Type
Experimental
Arm Title
Cohort 4: Participants receiving placebo
Arm Type
Placebo Comparator
Arm Title
Cohort 5: Participants receiving GSK3888130B at dose level 5
Arm Type
Experimental
Arm Title
Cohort 5: Participants receiving placebo
Arm Type
Placebo Comparator
Arm Title
Cohort 6: Participants receiving GSK3888130B at dose level 6
Arm Type
Experimental
Arm Title
Cohort 6: Participants receiving placebo
Arm Type
Placebo Comparator
Arm Title
Cohort 7: Participants receiving GSK3888130B at dose level 7
Arm Type
Experimental
Arm Title
Cohort 7: Participants receiving placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
GSK3888130B
Intervention Description
GSK3888130B will be administered.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be administered.
Primary Outcome Measure Information:
Title
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Time Frame
Up to 110 days
Title
Number of participants with clinically significant changes in laboratory parameters, vital signs and 12-lead electrocardiogram (ECG) findings
Time Frame
Up to 85 days
Secondary Outcome Measure Information:
Title
Serum concentrations of GSK3888130B
Time Frame
Up to 85 days
Title
Area under the concentration-time curve from time zero to time t (AUC[0 to t]) of GSK3888130B
Time Frame
Up to 85 days
Title
Maximum concentration (Cmax) of GSK3888130B in serum
Time Frame
Up to 85 days
Title
Time to Cmax (Tmax) of GSK3888130B
Time Frame
Up to 85 days
Title
Half-life (t1/2) of GSK3888130B
Time Frame
Up to 85 days
Title
Clearance (CL) of GSK3888130B
Time Frame
Up to 85 days
Title
Number of participants with positive anti-drug antibodies against GSK3888130B
Time Frame
Up to 85 days
Title
Change from Baseline in derived free Interleukin-7 (IL-7) protein levels over time
Time Frame
Baseline (Day 1) and up to 85 days
Title
Change in PD biomarker: T cell B-cell lymphoma 2 (Bcl-2) measured in blood over time
Time Frame
Baseline (Day 1) and up to 85 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name or Official Title & Degree
EU GSK Clinical Trials Call Center
Phone
+44 (0) 20 89904466
Email
GSKClinicalSupportHD@gsk.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Cambridge
ZIP/Postal Code
CB2 2GG
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
Disala Fernando

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.
IPD Sharing URL
http://clinicalstudydatarequest.com

Learn more about this trial

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

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