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

NCT05131971 | Completed Phase 1 Results

• 2 other identifiers: 2139602021-002063-22
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis; Colitis, Ulcerative

Keywords

Anti-Drug Antibodies; Double-blind; GSK3888130B; Pharmacodynamics; Pharmacokinetics; Single Dose Escalation

Outcome Measures

Primary Outcomes (10)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE is 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. An SAE is any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

  Up to 160 days

• Number of Participants With Clinically Significant Changes in Hematology Results

  Blood samples were collected for analysis of following hematology parameters: Basophils, Eosinophils, Hematocrit, Hemoglobin (Hg), Lymphocytes, Mean corpuscular Hg, Mean corpuscular volume, Monocytes, Platelet count, Red blood cell count, Reticulocytes, Total Neutrophils, and White blood cells count (WBC). Number of participants with clinically significant changes in hematology were reported. Clinical significance was determined by the investigator.

  Up to 85 days

• Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline

  Blood samples were collected for the analysis of CD4+ T Cell Counts. The CD4+ T Cell Counts were graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE). Grade 0: Above 0.5\*10\^9 cells/Liter (L), Grade 1: \<0.5 to 0.2\*10\^9 cells/L, Grade 2: \<0.2 to 0.05\*10\^9 cells/L, Grade 3: Below 0.05\*10\^9 cells/L. Baseline was defined as the latest pre-dose assessment. An increase was defined as an increase in grade relative to Baseline grade. Any worst-case post Baseline increase to Grade 1, Grade 2 and Grade 3 are presented.

  Baseline (Day 1) and up to 85 days

• Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline

  Blood samples were collected for the analysis of Creatinine. Creatinine was graded according to the NCI-CTCAE. Grade 0: \<1.5\* Baseline, or increase from Baseline \<26 micromoles per liter (umol/L), Grade 1: 1.5 to 1.9\* Baseline, or increase from Baseline \>=26 umol/L, Grade 2: 2.0 to 2.9\* Baseline, Grade 3: \>=3.0\* Baseline, or \>=354 umol/L. Baseline was defined as the latest pre-dose assessment. An increase was defined as an increase in grade relative to Baseline grade. Any worst-case post Baseline increase to Grade 1, Grade 2 and Grade 3 are presented.

  Baseline (Day 1) and up to 85 days

• Number of Participants With Clinically Significant Changes in Clinical Chemistry Results

  Blood samples were collected for analysis of following clinical chemistry parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Calcium, Total and Direct bilirubin, Glucose, Potassium, Sodium, Total protein, Lactate dehydrogenase, Haptoglobins and Urea. Number of participants with clinically significant changes in clinical chemistry were reported. Clinical significance was determined by the investigator.

  Up to 85 days

• Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline

  Urine samples were collected for analysis of Specific gravity, potential of hydrogen (pH), glucose, protein, erythrocytes, ketones, bilirubin, urobilinogen, nitrite, and leukocyte in urine by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase means any increase to trace, 1+, 2+ or 3+ post-Baseline relative to Baseline. Baseline was defined as the latest pre-dose assessment. Number of participants with worst-case any increase in urinalysis results post-Baseline relative to Baseline has been presented.

  Baseline (Day 1) and up to 85 days

• Number of Participants With Clinically Significant Changes in Vital Sign Results

  Vital signs included systolic and diastolic blood pressure, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring. Clinical significance was determined by the investigator.

  Up to 85 days

• Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA

  VZV-Nucleic acid from blood samples were extracted using the QIASymphony SP followed by TaqMan real time polymerase chain reaction (PCR) for amplification and detection. Murine cytomegalovirus (mCMV) was used as an internal control (IC) and was introduced during the extraction process. CMV-Nucleic acid was extracted using the QIASymphony SP/AS followed by automated set up of Artus real time PCR using the Rotor-Gene Q for amplification and detection. Baseline was defined as the latest pre-dose assessment. Number of participants with Positive CMV DNA and VZV DNA has been presented.

  Baseline (Day 1), Day 15 and Day 85

• Number of Participants With Positive Epstein-Barr Virus (EBV) DNA

  EBV DNA was assessed and qualitative data has been presented. Data has been categorized into 'Positive \>=LLQ' and 'Positive \< LLQ'. LLQ is lower limit of quantification. Participants who had EBV DNA values \>=LLQ were categorized as 'Positive \>=LLQ'. This represents a positive result that is above the assay limit of quantification. Participants who had EBV DNA values \<LLQ were categorized as 'Positive \<LLQ'. This represents a positive result that is below the assay limit of quantification. Baseline was defined as the latest pre-dose assessment.

  Baseline (Day 1), Day 15 and Day 85

• Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings

  Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT corrected interval. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.

  Up to 85 days

Secondary Outcomes (21)

• Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration

  Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85

• Serum Concentrations of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration

  Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85

• Serum Concentrations of GSK3888130B for Dose Levels 6 and 7 IV Administration

  Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85

• 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

  Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85

• AUC(0 to t) for Dose Levels 3 and 5 Subcutaneous Administration

  Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85

Study Arms (14)

Cohort 1: Participants receiving GSK3888130B at dose level 1

EXPERIMENTAL

Drug: GSK3888130B

Cohort 1: Participants receiving placebo

PLACEBO COMPARATOR

Drug: Placebo

Cohort 2: Participants receiving GSK3888130B at dose level 2

EXPERIMENTAL

Drug: GSK3888130B

Cohort 2: Participants receiving placebo

PLACEBO COMPARATOR

Drug: Placebo

Cohort 3: Participants receiving GSK3888130B at dose level 3

EXPERIMENTAL

Drug: GSK3888130B

Cohort 3: Participants receiving placebo

PLACEBO COMPARATOR

Drug: Placebo

Cohort 4: Participants receiving GSK3888130B at dose level 4

EXPERIMENTAL

Drug: GSK3888130B

Cohort 4: Participants receiving placebo

PLACEBO COMPARATOR

Drug: Placebo

Cohort 5: Participants receiving GSK3888130B at dose level 5

EXPERIMENTAL

Drug: GSK3888130B

Cohort 5: Participants receiving placebo

PLACEBO COMPARATOR

Drug: Placebo

Cohort 6: Participants receiving GSK3888130B at dose level 6

EXPERIMENTAL

Drug: GSK3888130B

Cohort 6: Participants receiving placebo

PLACEBO COMPARATOR

Drug: Placebo

Cohort 7: Participants receiving GSK3888130B at dose level 7

EXPERIMENTAL

Drug: GSK3888130B

Cohort 7: Participants receiving placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

GSK3888130B DRUG

GSK3888130B will be administered.

Cohort 1: Participants receiving GSK3888130B at dose level 1; Cohort 2: Participants receiving GSK3888130B at dose level 2; Cohort 3: Participants receiving GSK3888130B at dose level 3; Cohort 4: Participants receiving GSK3888130B at dose level 4; Cohort 5: Participants receiving GSK3888130B at dose level 5; Cohort 6: Participants receiving GSK3888130B at dose level 6; Cohort 7: Participants receiving GSK3888130B at dose level 7

Placebo DRUG

Placebo will be administered.

Cohort 1: Participants receiving placebo; Cohort 2: Participants receiving placebo; Cohort 3: Participants receiving placebo; Cohort 4: Participants receiving placebo; Cohort 5: Participants receiving placebo; Cohort 6: Participants receiving placebo; Cohort 7: Participants receiving placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

MeSH Terms

Conditions

Multiple Sclerosis; Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This will be a double-blind study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to receive either GSK3888130B or placebo in single ascending dose cohorts.

Study Record Dates

• First Submitted: October 27, 2021
• First Posted: November 23, 2021
• Study Start: November 1, 2021
• Primary Completion: October 12, 2023
• Study Completion: October 12, 2023
• Last Updated: March 26, 2025
• Results First Posted: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

GB (1)