Single Ascending Doses Study of Anti- Interleukin-7 Receptor α Monoclonal Antibody (GSK2618960) in Healthy Volunteers

NCT02293161 | Completed Phase 1

• 1 other identifier: 200902
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

GSK2618960 is a humanized Immunoglobulin G 1 ( IgG1) monoclonal antibody (mAb) that binds to the alpha component (CD127) of the heterodimeric Interleukin-7 receptor (IL-7R). It is being developed for the treatment of autoimmune indications. This study is intended to further explore the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of single ascending doses GSK2618960 in healthy volunteers beyond those already evaluated in I7R116702 (First Time In Human study). The study is anticipated to enrol 18 subjects in total, with 9 subjects in each of the two cohorts.

Conditions

Autoimmune Diseases

Keywords

Interleukin-7 Receptor α; monoclonal antibody

Outcome Measures

Primary Outcomes (11)

• Number of Participants with Adverse events (AE)

  An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product

  Up to Day 169

• Absolute values of vital signs

  Vital signs includes systolic and diastolic blood pressure, pulse rate and body temperature.

  Up to Day 169

• Change from baseline in vital signs

  Vital signs includes systolic and diastolic blood pressure, pulse rate and body temperature.

  Baseline (Day1) and up to Day 169

• Absolute values of Electrocardiogram (ECG) parameters

  Single 12-lead ECGs will be obtained.

  Up to Day 169

• Change from baseline in ECG parameters

  Single 12-lead ECGs will be obtained.

  Baseline (Day1) and up to Day 169

• Absolute values of haematology

  Haematology parameters includes Platelet Count, Red blood cells (RBC) Count, White blood cells Count (absolute) (WBC), Haemoglobin and Haematocrit

  Up to Day 169

• Change from baseline in haematology

  Haematology parameters includes Platelet Count, RBC, WBC, Haemoglobin and Haematocrit

  Baseline (Day -1) and up to Day 169

• Absolute values of clinical chemistry

  Clinical chemistry includes Blood urea nitrogen, Potassium, Aspartate aminotransferase (SGOT), Total and direct bilirubin, Creatinine, Chloride, Alanine aminotransferase (SGPT), Albumin, Glucose, Total Carbon dioxide, Gamma glutamyltransferase, Total Protein, Sodium, Calcium and Alkaline phosphatase

  Up to Day 169

• Change from baseline in clinical chemistry

  Clinical chemistry includes Blood urea nitrogen, Potassium, SGOT, Total and direct bilirubin, Creatinine, Chloride, SGPT, Albumin, Glucose, Total Carbon dioxide, Gamma glutamyltransferase, Total Protein, Sodium, Calcium and Alkaline phosphatase

  Baseline (Day -1) and up to Day 169

• Absolute values of urinalysis

  Urinalysis includes Specific gravity, pH, glucose, protein, blood and ketones by dipstick, Microscopic examination (if blood or protein is abnormal)

  Up to Day 169

• Change from baseline in urinalysis

  Urinalysis includes Specific gravity, pH, glucose, protein, blood and ketones by dipstick, Microscopic examination (if blood or protein is abnormal)

  Baseline (Day -1) and up to Day 169

Secondary Outcomes (9)

• Composite of PK parameters

  Up to Day 29

• Duration of full receptor occupancy (RO) for Cohort A

  Up to Day 43

• Duration of full RO for Cohort B

  Up to Day 57

• Relationship between dose/exposure and duration of full RO for Cohort A

  Up to Day 43

• Relationship between dose/exposure and duration of full RO for Cohort B

  Up to Day 57

Study Arms (4)

Cohort A GSK2618960

EXPERIMENTAL

Subjects will receive GSK2618960 0.6 milligram per kilogram (mg/kg)

Drug: GSK2618960

Cohort A Placebo

PLACEBO COMPARATOR

Subjects will receive Sodium Chloride Intravenous as placebo

Drug: Placebo

Cohort B GSK2618960

EXPERIMENTAL

Subjects will receive GSK2618960,planned dose being 2mg/kg. However, actual dose level for Cohort B may be adjusted based on the emerging data on safety, tolerability, PK and RO from Cohort A. The maximum dose will not exceed 2.4 mg/kg (i.e. a 4-fold dose escalation from 0.6 mg/kg)

Drug: GSK2618960

Cohort B Placebo

PLACEBO COMPARATOR

Subjects will receive Sodium Chloride Intravenous as placebo

Drug: Placebo

Interventions

GSK2618960 DRUG

GSK2618960 will be provided as 100 mg/mL solution for injection to be administered as single dose IV infusion that has to be diluted at the study site with placebo

Cohort A GSK2618960; Cohort B GSK2618960

Placebo DRUG

It is Sodium Chloride Intravenous Infusion

Cohort A Placebo; Cohort B Placebo

Eligibility Criteria

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

You may qualify if:

• Males aged between 18 and 65 years of age inclusive, at the time of signing the informed consent OR females of non-child bearing potential aged between 18 and 65 years of age at the time of signing the informed consent.
• Non-childbearing potential defined as:- pre-menopausal females with a documented tubal ligation or hysterectomy, or post-menopausal defined as 24 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \>40 milli-international units (MIU) per millilitre (mL) and oestradiol \<40 picograms (pg) /mL (\< 140 picomole/liter) is confirmatory. \[Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt must discontinue HRT to allow confirmation of postmenopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their postmenopausal status, they can resume use of HRT during the study.\]
• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Protocol. This criterion must be followed from the time of the first dose of study medication until 5 half-lives after the infusion (Week 16 visit).

You may not qualify if:

• White blood cell count \>=Lower Limit of Normal (LLN), including both lymphocyte and neutrophil counts \>=LLN.
• Body weight \>=50 kilogram (kg) and body mass index (BMI) within the range 19.0 - 32.0 kilogram / square meter (kg/m\^2) (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Subjects with a confirmed positive vaccination status for tetanus, diphtheria, pertussis, measles, mumps, rubella, pneumococcus and meningococcus (or consent to vaccination)
• Criteria Based Upon Medical Histories
• Current evidence of ongoing or acute infection within 3 months prior to the first dose of study drug, such as: serious local infection (e.g. cellulitis, abscess); systemic infection \[e.g. pneumonia, septicaemia, Tuberculosis (TB)\].
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A QT duration corrected for heart rate by Fridericia's formula (QTcF) \>450 millisecond (msec) based on either single or averaged QTcF values of triplicate ECGs obtained over a brief recording period.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint \~240 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.
• Previous history of anaphylaxis and severe allergic reaction.
• Receipt of live vaccination within 1 month of screening or plan to receive live vaccination at any time during the study i.e. 6 months following dosing (which covers the period when the predicted target duration of receptor occupancy is \>= 95%).
• Subjects from a high risk area of the world for tuberculosis or have history of tuberculosis or have close family members with confirmed TB infection or positive at screening by Quantiferon testing (an indeterminate test result at screen may be repeated once).
• Criteria Based Upon Diagnostic Assessments
• A positive pre-study Hepatitis B surface and/or core antibody or positive Hepatitis C antibody result within 3 months of screening

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

Related Publications (1)

• Ellis J, van Maurik A, Fortunato L, Gisbert S, Chen K, Schwartz A, McHugh S, Want A, Santos Franco S, Oliveira JJ, Price J, Coles A, Brown K, Su D, Craigen JL, Yang J, Brett S, Davis B, Cheriyan J, Kousin-Ezewu O, Gray F, Thompson PW, Fernando D. Anti-IL-7 receptor alpha monoclonal antibody (GSK2618960) in healthy subjects - a randomized, double-blind, placebo-controlled study. Br J Clin Pharmacol. 2019 Feb;85(2):304-315. doi: 10.1111/bcp.13748. Epub 2018 Dec 3.

  PMID: 30161291 DERIVED

Related Links

• Results for study 200902 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Autoimmune Diseases

Interventions

GSK2618960

Condition Hierarchy (Ancestors)

Immune System 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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2014
• First Posted: November 18, 2014
• Study Start: November 11, 2014
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: May 9, 2017

Record last verified: 2017-05

Locations

GB (1)