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

NCT ID: NCT02293161

Last Updated: 2017-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-11
• Study Completion Date: 2015-09-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cohort A GSK2618960

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

Group Type: EXPERIMENTAL

GSK2618960

Intervention Type: 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 Placebo

Subjects will receive Sodium Chloride Intravenous as placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

It is Sodium Chloride Intravenous Infusion

Cohort B GSK2618960

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)

Group Type: EXPERIMENTAL

GSK2618960

Intervention Type: 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 B Placebo

Subjects will receive Sodium Chloride Intravenous as placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

It is Sodium Chloride Intravenous Infusion

Interventions

GSK2618960

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

Intervention Type: DRUG

Placebo

It is Sodium Chloride Intravenous Infusion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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).

Exclusion Criteria

• 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
• A positive pre-study drug screen.
• A positive test for Human Immunodeficiency Virus (HIV) antibody. Other Criteria
• Smokers who would not be able to refrain from smoking whilst in the phase I unit.
• Unable to refrain from the use of prescription or non-prescription drugs (unless permitted as per protocol
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day "rolling" period.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in 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 four new chemical entities within 12 months prior to the first dosing day.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Cambridge, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 30161291 (View on PubMed)

Other Identifiers

200902

Identifier Type: -

Identifier Source: org_study_id