Single Dose Escalation Trial to Evaluate the Safety, Tolerability Pharmacokinetics and Pharmacodynamics of GSK3050002

NCT01984047 | Completed Phase 1

• 1 other identifier: 200784
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of GSK3050002 in humans. Subjects will attend the clinical unit for a screening visit and if eligible and consenting, will attend to participate in the study within 30 days. Subjects will be admitted to the clinical unit the evening prior to dosing when each subject will receive a single intravenous dose of GSK3050002 or placebo, then remain in house under supervision until discharged on Day 3. Subjects will then return for 7 outpatient visits scheduled over the following 81 days. Finally, the follow-up visit will be 7-14 days following the last visit.

Conditions

Colitis, Ulcerative

Keywords

safety; GSK3050002; CCR6 receptor; single dose escalation; Phase 1; CCL20

Outcome Measures

Primary Outcomes (5)

• Number of subjects with adverse events

  Adverse events will be collected from the start of study treatment until the follow-up contact

  Up to Day 98

• Laboratory measurements

  Clinical laboratory assessments will include haematology, clinical chemistry, urinalysis and other screening tests

  Up to Day 98

• Electrocardiogram (ECG) assessment as a measure of safety

  Triplicate 12-lead ECG will be recorded before dosing on Day 1 (Pre-dose) and a single 12-lead ECG will be obtained at all other timepoints

  Up to Day 98

• Vital signs as a measure of safety

  Vital sign measurements will include systolic and diastolic blood pressure, temperature, and pulse rate

  Up to Day 98

• Pharmacokinetic (PK) parameters after a single intravenous dose of GSK3050002

  The following PK parameters will be determined: maximum observed serum concentration (Cmax), time to Cmax (tmax), area under the serum concentration-time curve (AUC\[0-t\] and AUC\[0-infinity\]), and apparent terminal phase half-life (t1/2)

  Day 1, Day 2, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42, Day 56 and Day 84

Secondary Outcomes (2)

• Chemokine (C-C motif) ligand 20 (CCL20) levels in blood

  Up to Day 87

• Immunogenicity development as assessed from anti-drug antibody

  Up to Day 87

Study Arms (6)

GSK3050002 0.1 mg

EXPERIMENTAL

Six subjects in this cohort will receive a single dose of GSK3050002 0.1 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects (i.e. 1 subject will be dosed with GSK3050002 and 1 with placebo before the remainder of the cohort is dosed) will be used in the cohort.

Drug: GSK3050002; Drug: Placebo

GSK3050002 0.5 mg

EXPERIMENTAL

Six subjects in this cohort will receive a single dose of GSK3050002 0.5 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.

Drug: GSK3050002; Drug: Placebo

GSK3050002 1 mg

EXPERIMENTAL

Six subjects in this cohort will receive a single dose of GSK3050002 1 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort

Drug: GSK3050002; Drug: Placebo

GSK3050002 5 mg

EXPERIMENTAL

Six subjects in this cohort will receive a single dose of GSK3050002 5 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.

Drug: GSK3050002; Drug: Placebo

GSK3050002 10 mg

EXPERIMENTAL

Six subjects in this cohort will receive a single dose of GSK3050002 10 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.

Drug: GSK3050002; Drug: Placebo

GSK3050002 20 mg

EXPERIMENTAL

Six subjects in this cohort will receive a single dose of GSK3050002 20 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.

Drug: GSK3050002; Drug: Placebo

Interventions

GSK3050002 DRUG

GSK3050002 is a white to off-white lyophilized powder that will be reconstituted with sterile water for intravenous infusion. It is available in the concentrations of 0.1 milligram (mg)/kg, 0.5 mg/kg, 1 mg/kg, 5 mg/kg, 10 mg/kg and 20 mg/kg.

GSK3050002 0.1 mg; GSK3050002 0.5 mg; GSK3050002 1 mg; GSK3050002 10 mg; GSK3050002 20 mg; GSK3050002 5 mg

Placebo DRUG

Placebo contains normal saline (0.9% sodium chloride) for intravenous infusion

GSK3050002 0.1 mg; GSK3050002 0.5 mg; GSK3050002 1 mg; GSK3050002 10 mg; GSK3050002 20 mg; GSK3050002 5 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.

You may not qualify if:

• Body mass index (BMI) within the range 18 - 29 kilogram per meter square \[kg/m\^2\] (inclusive).
• Male subjects with female partners of child-bearing potential must agree to use one of the listed contraception methods. This criterion must be followed for 1 month prior to the first dose of study medication for 15 weeks post dose.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Suitable for cannulation and with adequate venous access.
• Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin \<= 1.5xUpper limit of Normal \[ULN\] (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Based on a single ECG QTcF \< 450 milliseconds (msec).
• Criteria Based Upon Medical Histories
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of \>21 units. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 milliliter \[mL\]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• History of severe drug allergies including type 1 hypersensitivity reaction to parental administration of contrast agents, human or murine proteins or monoclonal antibodies.
• Subject has acne which requires prescription treatment
• Criteria Based Upon Diagnostic Assessments
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• A positive pre-study drug/alcohol screen.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Eisai Inc.: collaborator

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

Related Publications (1)

• Laffan SB, Thomson AS, Mai S, Fishman C, Kambara T, Nistala K, Raymond JT, Chen S, Ramani T, Pageon L, Polsky R, Watkins M, Ottolangui G, White JR, Maier C, Herdman M, Bouma G. Immune complex disease in a chronic monkey study with a humanised, therapeutic antibody against CCL20 is associated with complement-containing drug aggregates. PLoS One. 2020 Apr 23;15(4):e0231655. doi: 10.1371/journal.pone.0231655. eCollection 2020.

  PMID: 32325480 DERIVED

Related Links

• Results for study 200784 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

GSK3050002

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2013
• First Posted: November 14, 2013
• Study Start: January 10, 2014
• Primary Completion: February 23, 2015
• Study Completion: February 23, 2015
• Last Updated: July 24, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• 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)