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Healthy VolunteersPhase 1NCT04138043

Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of GSK2330811 in Healthy Japanese Participants

A Phase 1 study testing GSK2330811 in people with Healthy Volunteers, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a randomized, double-blind (sponsor-open), placebo-controlled, single-center study involving Japanese participants. The purpose of the study is to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity after a single subcutaneous (SC) dose of GSK2330811 in healthy… Read more about this study

Who is it for?
Ages 18 to 65 years, men onlyHealthy volunteers can take part
Conditions the study is for
Healthy Volunteers
What is being tested?
GSK2330811
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
9 participants
Where
1 siteUnited Kingdom
Study dates
5 Dec 2019to 28 May 2020
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 65 years
  • Men only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
  • Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests and 12-lead ECGs.
  • A participant with a clinical abnormality or laboratory parameters outside the reference range for the healthy population being studied that is not specifically listed in the inclusion or exclusion criteria may be included if the investigator and sponsor medical monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or interpretation.
  • Participants with body weight >=45 kilogram (kg) and body mass index (BMI) within the range 18.5-29.9 kg per square meter.
  • Male participants.
  • Participants capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
  • Participants with Japanese ancestry, defined as having been born in Japan, being descendants of four ethnic Japanese grandparents and two ethnic Japanese parents, holding a Japanese passport or identity papers, and being able to speak Japanese. Participants should have lived outside Japan for less than 10 years at the time of screening.

Who cannot join

  • Participants with sensitivity to any of the study treatments or components there of (including humanized monoclonal antibodies) or history of severe post treatment hypersensitivity reactions including erythema multiforme major, linear immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis and exfoliative dermatitis.
  • Participants with any other history of significant allergy that in the opinion of the investigator contraindicates their participation in this study.
  • Participants with an active infection or a history of serious infections as follows: Use of antimicrobials (antibacterials, antivirals, antifungals or antiparasitic agents) for an infection within 30 days prior to Day 1. Topical treatments may be allowed at the Investigator's discretion (in consultation with the Medical Monitor); A history of opportunistic or recurrent infections, as determined by the investigator; Currently active or unresolved infection (participants with 'trivial' infections such as tinea pedis may be eligible at the discretion of the investigator); Symptomatic herpes zoster within 3 months prior to screening; History of tuberculosis (TB) (active or latent) irrespective of treatment status; and a positive diagnostic TB test at screening (defined as a positive QuantiFERON test).
  • Participants with any planned major surgical procedure during the study.
  • Participants with a history of hematological disease, for example (but not limited to): significant anemia, platelet disorders including drug-induced thrombocytopenia or primary immune thrombocytopenia and coagulation disorders including von Willebrand's disease.
  • Participants with a history of carcinoma in situ and malignant disease, with the exception of adequately treated non-metastatic basal or squamous cell cancer of the skin that has been fully treated and shows no evidence of recurrence after 3 years.
Show all 21Show fewer
  • Participants with QTc >450 millisecond (msec) at screening.
  • Participants with use of prescription or non-prescription drugs (including recreational drugs and herbal medications) within 7 days or 5 half-lives (whichever is longer) prior to Day 1 unless in the opinion of the investigator (in consultation with the sponsor medical monitor) the medication will not interfere with the study or compromise participant safety. Paracetamol at doses of <=4 grams per day, and occasional use of non-steroidal anti-inflammatory drugs (NSAIDs) at licensed doses, are permitted.
  • Participants who received live vaccination within 4 weeks prior to Day 1, or any plan to receive a live vaccination during the study (up to and including to the last follow-up visit).
  • Participation in a clinical trial and has received an investigational medicine product (IMP) within the following time period prior to Day 1: 3 months, 5 half-lives, or twice the duration of the biological effect of the IMP (whichever is longer).
  • Participants with exposure to more than 4 new chemical entities within 12 months prior to Day 1.
  • Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 3 months.
  • Participants with platelet count or hemoglobin below the normal range at any time during screening.
  • Participants with alanine aminotransaminase (ALT) >1.5 times upper limit of normal (ULN) at any time during screening.
  • Participants with bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent) at any time during screening.
  • Participants with presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb), or positive hepatitis C virus (HCV) antibody result at screening. Participants with positive HCV antibody due to prior resolved disease can be enrolled only if a confirmatory negative HCV Ribonucleic acid (RNA) test is obtained.
  • Participants with positive human immunodeficiency virus (HIV) antibody test at screening.
  • Participants with positive pre-study drug or alcohol screen.
  • Participants with history of regular alcohol consumption within 6 months of the screening visit in excess of an average weekly intake of >21 units. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Participants planning to travel to regions of high endemic infection, as determined by the investigator, for the duration of the study.
  • Participants with unstable lifestyle factors, to the extent that in the opinion of the investigator they would interfere with the ability of a participant to complete the study.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site
  • GSK Investigational Site

    London, NW10 7EW

Other trials in United Kingdom

About this study

Official title: A Phase 1, Randomised, Double-blind, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Subcutaneous Doses of GSK2330811 in Healthy Japanese Participants

This is a randomized, double-blind (sponsor-open), placebo-controlled, single-center study involving Japanese participants. The purpose of the study is to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity after a single subcutaneous (SC) dose of GSK2330811 in healthy Japanese participants. GSK2330811 is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that binds and inhibits the action of Oncostatin M (OSM) and is being developed for the treatment of Crohn's disease (CD) and Systemic sclerosis (SSc). Participants will be randomized to receive either GSK2330811 (450 milligram [mg]) or placebo in an approximate ratio of 7:3.

Being tested
Placebo, GSK2330811
Keywords
GSK2330811, Healthy participants, Japanese, Pharmacokinetics, Safety, Subcutaneous dose

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Placebo is 0.9 percent sodium chloride solution. It will be administered as SC injection to abdomen by study personnel. Three injections will be used to match active doses.

  • GSK2330811Drug

    GSK2330811 will be available as SC injection 150 mg/mL.

Study groups in NCT04138043
Study groupRoleWhat they receive
GSK2330811 450 mgExperimentalParticipants will receive a single 450 mg SC dose of GSK2330811, administered as three separate SC injections of 150 milligrams per milliliter [mg/mL]).
Receives: Drug: GSK2330811
PlaceboPlacebo comparatorParticipants will receive GSK2330811 matching placebo administered as three separate SC injections.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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. A SAE is defined as any untoward medical occurrence 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, congenital anomaly/birth defect, any other situation according to medical or scientific judgment. Safety Population consisted of all randomized participants who received at least one dose of study treatment.

    Measured: Up to Day 126

  2. Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline

    Vital signs were measured in semi-supine position after 5 minutes of rest and included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR). Participants were counted in the worst case category that their value changed to low, within range or high, unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "Within Range or No Change" category. Participants were counted twice if values changed 'To Low' and 'To High', so the percentages were not added up to 100 percent (%). Participants with missing Baseline values were assumed as within range value. PCI ranges were: SBP (lower: <85, upper: >160 millimeter of mercury [mmHg]); DBP (lower: <45, upper: >100 mmHg); HR (lower: <40, upper: >110 beats per minute). Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment.

    Measured: Baseline (Pre-dose, Day 1) and up to Day 126

  3. Change From Baseline in Body Temperature

    Body temperature was measured in semi-supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Pre-dose, Day 1), Day 1: 1, 4, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

  4. Number of Participants With Worst Case Abnormal Electrocardiogram (ECG) Findings

    12-lead ECGs were recorded in semi-supine position using an ECG machine. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal laboratory findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

    Measured: Up to Day 126

  5. Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters

    Blood samples were collected for the analysis of clinical chemistry parameters. Clinical chemistry parameters were summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling. Higher grade indicates more severity. Clinical chemistry parameters included: total bilirubin, calcium, creatinine and triglycerides.

    Measured: Up to Day 126

  6. Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters

    Blood samples were collected for the analysis of the following hematology parameters: hemoglobin (Hb), lymphocytes (Lympho), platelet count (PC), neutrophil count (Neutro) and White Blood Cell count (WBC). The laboratory parameters were graded according to NCI-CTCAE version 5.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severity. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. An increase was defined as an increase in CTCAE Grade relative to Baseline Grade.

    Measured: Baseline (Pre-dose, Day 1) and up to Day 126

  7. Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline

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

    Measured: Baseline (Pre-dose, Day 1) and up to Day 126

Secondary outcomes (12)
  1. Maximum Plasma Concentration (Cmax) for GSK2330811

    Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis. Pharmacokinetic Population consisted of all participants in the Safety population who received at least one active dose of study treatment and had at least 1 non-missing PK assessment.

    Measured: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

  2. Area Under the Plasma Concentration Time-curve From Time Zero to Infinity (AUC[0-infinity]) for GSK2330811

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.

    Measured: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

  3. Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) for GSK2330811

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.

    Measured: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

  4. Apparent Systemic Clearance (CL/F) for GSK2330811

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.

    Measured: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

  5. Time to Cmax (Tmax) for GSK2330811

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.

    Measured: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

  6. Terminal Half-life (t1/2) for GSK2330811

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.

    Measured: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

  7. Apparent Volume of Distribution at Steady State (Vss/F) for GSK2330811

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.

    Measured: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

  8. Number of Participants With Positive Anti-GSK2330811 Antibodies

    Serum samples were analyzed for the presence of anti-GSK2330811 antibodies using an antibody binding assay. 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 the specificity using the confirmation assay. Number of participants with confirmed positive anti-GSK2330811 antibodies are presented.

    Measured: Up to Day 126

  9. Platelet Count Nadir for GSK2330811

    Blood samples were collected at indicated time points for analysis of platelet count nadir for GSK2330811. Nadir was defined as the lowest post-Baseline value of the platelet count.

    Measured: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

  10. Time to Platelet Count Nadir for GSK2330811

    Blood samples were collected at indicated time points for analysis of platelet count nadir for GSK2330811. Nadir was defined as the lowest post-Baseline value of the platelet count. Time to nadir was defined as Study Day of Nadir minus 1.

    Measured: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

  11. Hemoglobin Nadir for GSK2330811

    Blood samples were collected at the indicated time points for analysis of hemoglobin nadir for GSK2330811. Nadir was defined as the lowest post-Baseline value of the hemoglobin.

    Measured: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

  12. Time to Hemoglobin Nadir for GSK2330811

    Blood samples were collected at indicated time points for analysis of hemoglobin nadir for GSK2330811. Nadir was defined as the lowest post-Baseline value of the hemoglobin. Time to nadir was defined as Study Day of Nadir minus 1.

    Measured: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Oct 2019
  2. Study start5 Dec 2019
  3. Primary completion28 May 2020
  4. Study completion28 May 2020

Resources

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
Parallel groups
Model description
This is a parallel group study. Participants will be randomized to receive either GSK2330811 (450 mg) or placebo in an approximate ratio of 7:3.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04138043
Sponsor's protocol ID
208564
Status last verified
Apr 2021
First submitted
22 Oct 2019
Last updated
24 May 2021
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.

Publications

  • Thorsted A, Zecchin C, Berges A, Karlsson MO, Friberg LE. Predicting the Long-Term Effects of Therapeutic Neutralization of Oncostatin M on Human Hematopoiesis. Clin Pharmacol Ther. 2024 Sep;116(3):703-715. doi: 10.1002/cpt.3246. Epub 2024 Mar 19.

    PubMed 38501358

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK2330811 in people with Healthy Volunteers, 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 7 inclusion and 21 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 24 May 2021. 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 24 May 2021). 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 Day 126). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04138043, which also lists 1 linked publication.

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 24 May 2021.

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