Multiple SclerosisPhase 1NCT05131971
A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics (PD) of GSK3888130B in Healthy Participants
A Phase 1 study testing GSK3888130B in people with Multiple Sclerosis and Colitis, Ulcerative, run by GlaxoSmithKline at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis, Colitis, Ulcerative
- What is being tested?
- GSK3888130B
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Nov 2021to 12 Oct 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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, 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- GSK3888130B, Placebo
- Keywords
- Anti-Drug Antibodies, Double-blind, GSK3888130B, Pharmacodynamics, Pharmacokinetics, Single Dose Escalation
- Medical subject headings
- Multiple Sclerosis, Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK3888130BDrug
GSK3888130B will be administered.
PlaceboDrug
Placebo will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Participants receiving GSK3888130B at dose level 1 | Experimental | Not described Receives: Drug: GSK3888130B |
| Cohort 1: Participants receiving placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Cohort 2: Participants receiving GSK3888130B at dose level 2 | Experimental | Not described Receives: Drug: GSK3888130B |
| Cohort 2: Participants receiving placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Cohort 3: Participants receiving GSK3888130B at dose level 3 | Experimental | Not described Receives: Drug: GSK3888130B |
| Cohort 3: Participants receiving placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Cohort 4: Participants receiving GSK3888130B at dose level 4 | Experimental | Not described Receives: Drug: GSK3888130B |
| Cohort 4: Participants receiving placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Cohort 5: Participants receiving GSK3888130B at dose level 5 | Experimental | Not described Receives: Drug: GSK3888130B |
| Cohort 5: Participants receiving placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Cohort 6: Participants receiving GSK3888130B at dose level 6 | Experimental | Not described Receives: Drug: GSK3888130B |
| Cohort 6: Participants receiving placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Cohort 7: Participants receiving GSK3888130B at dose level 7 | Experimental | Not described Receives: Drug: GSK3888130B |
| Cohort 7: Participants receiving placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 85 days
Secondary outcomes (21)
Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Blood samples were collected at indicated time points for measurement of serum concentrations of GSK3888130B following intravenous administration. Pharmacokinetic (PK) Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable [NQ] values were considered as non-missing values).
Measured: 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
Blood samples were collected at indicated time points for measurement of serum concentrations of GSK3888130B following subcutaneous administration.
Measured: 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
Blood samples were collected at indicated time points for measurement of serum concentrations of GSK3888130B following intravenous administration. Pharmacokinetic (PK) Population consisted of all participants in the Safety analysis set who had received an active study intervention and had at least 1 non-missing post dose PK assessment (Non-quantifiable [NQ] values were considered as non-missing values).
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration.
Measured: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
AUC(0 to t) for Dose Levels 6 and 7 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Measured: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Maximum Observed Plasma Concentration (Cmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Cmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration.
Measured: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Cmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Measured: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Time to Cmax (Tmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Tmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration.
Measured: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Tmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Measured: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Half-life (t1/2) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
t1/2 of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration.
Measured: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
t1/2 of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Measured: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Clearance (CL) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Clearance Factor (CL/F) of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following subcutaneous administration.
Measured: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
CL of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3888130B following intravenous administration.
Measured: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B
Serum samples were collected for the determination of anti-drug antibodies (ADA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample. Baseline was defined as the latest pre-dose assessment.
Measured: Baseline (Day 1), Day 15, Day 29, Day 57 and Day 85
Percent Peak Reduction From Baseline in Derived Free Interleukin 7 (IL 7) in Blood
Free IL-7 levels were derived from total IL-7 and total GSK3888130B concentrations (named as Derived Free IL-7) over time using a nonlinear mixed effects modelling approach. A target-mediated drug disposition model was used to fit the total IL-7 and total GSK3888130B assay concentration data to derive the free-IL-7 concentrations. Peak reduction relative to Baseline (Percent change) was calculated for each participant as; Peak reduction = (1 - minimum [Free IL7/IL7 Baseline])*100. Baseline was defined as the latest pre-dose assessment.
Measured: Baseline (Day 1) and up to 8 hours
Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood
Blood samples were collected at indicated time points to measure Bcl-2 Expression in CD4+ T Cells as median fluorescence intensity (MdFI). Baseline was defined as the latest pre-dose assessment. MdFI values as a measure of Bcl-2 expression in CD4+ T cells was measured by flow cytometry. Placebo arms were combined as pre-specified in reporting and analysis plan.
Measured: Baseline (Day 1) and Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2021
- Study start1 Nov 2021
- Primary completion12 Oct 2023
- Study completion12 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Participants will be randomized to receive either GSK3888130B or placebo in single ascending dose cohorts.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05131971
- Sponsor's protocol ID
- 213960
- Other IDs
- 2021-002063-22
- Status last verified
- Mar 2025
- First submitted
- 27 Oct 2021
- Last updated
- 26 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05131971
- Acronym / sponsor ID
- 213960
- Conditions
- Multiple Sclerosis, Colitis, Ulcerative
- Keywords
- Anti-Drug Antibodies, Double-blind, GSK3888130B, Pharmacodynamics, Pharmacokinetics, Single Dose Escalation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 1 Nov 2021 (actual)
- Primary completion
- 12 Oct 2023 (actual)
- Study completion
- 12 Oct 2023 (actual)
- First posted
- 23 Nov 2021 (actual)
- Results
- Posted 26 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 14
- Model description
- Participants will be randomized to receive either GSK3888130B or placebo in single ascending dose cohorts.
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK3888130BGSK3888130B will be administered. | Drug | 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 |
| PlaceboPlacebo will be administered. | Drug | 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 |
Primary outcome
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 160 days
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.
Number of Participants With Clinically Significant Changes in Hematology Results
Time frame: Up to 85 days
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.
Number of Participants With Worst-case Cluster of Differentiation (CD) 4+ T Cell Counts Results by Maximum Grade Increase Post-Baseline Relative to Baseline
Time frame: Baseline (Day 1) and up to 85 days
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.
Number of Participants With Worst-case Creatinine Results by Maximum Grade Increase Post-Baseline Relative to Baseline
Time frame: Baseline (Day 1) and up to 85 days
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.
Number of Participants With Clinically Significant Changes in Clinical Chemistry Results
Time frame: Up to 85 days
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.
Number of Participants With Worst-case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline
Time frame: Baseline (Day 1) and up to 85 days
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.
Number of Participants With Clinically Significant Changes in Vital Sign Results
Time frame: Up to 85 days
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.
Number of Participants With Positive Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) and Varicella Zoster Virus (VZV) DNA
Time frame: Baseline (Day 1), Day 15 and Day 85
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.
Number of Participants With Positive Epstein-Barr Virus (EBV) DNA
Time frame: Baseline (Day 1), Day 15 and Day 85
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.
Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
Time frame: Up to 85 days
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.
21 secondary outcomes
Serum Concentrations of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
AUC(0 to t) for Dose Levels 6 and 7 Intravenous Administration
Time frame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Maximum Observed Plasma Concentration (Cmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Cmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
Time frame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Cmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
Time frame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Time to Cmax (Tmax) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Tmax of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
Time frame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Tmax of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
Time frame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Half-life (t1/2) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
t1/2 of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
Time frame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
t1/2 of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
Time frame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Clearance (CL) of GSK3888130B for Dose Levels 1, 2 and 4 Intravenous Administration
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Clearance Factor (CL/F) of GSK3888130B for Dose Levels 3 and 5 Subcutaneous Administration
Time frame: Day 1: Pre-dose, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
CL of GSK3888130B for Dose Levels 6 and 7 Intravenous Administration
Time frame: Day 1: Pre-dose, 30 minutes, 1 hour, 4, 8, 12, 24, 48 hours; Days 6, 8, 10, 15, 21, 29, 57, and 85
Number of Participants With Positive Anti-drug Antibodies Against GSK3888130B
Time frame: Baseline (Day 1), Day 15, Day 29, Day 57 and Day 85
Percent Peak Reduction From Baseline in Derived Free Interleukin 7 (IL 7) in Blood
Time frame: Baseline (Day 1) and up to 8 hours
Median Fluorescence Intensity (MdFI) of B-cell Lymphoma 2 (Bcl-2) Expression in CD4+ T Cells in Blood
Time frame: Baseline (Day 1) and Day 15
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK3888130B in people with Multiple Sclerosis and Colitis, Ulcerative, run by GlaxoSmithKline at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Up to 160 days). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2025.