A Study to Investigate the Safety Tolerability Pharmacokinetics, and Pharmacodynamics of Inhaled and Intravenous GSK2862277 in Healthy Volunteers

NCT01818024 | Completed Phase 1

• 1 other identifier: 116343
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a 3 part study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and repeat doses of GSK2862277 administered via inhalation (IH) or intravenous (IV) routes in healthy subjects. Part 1 of this study will involve an initial assessment of safety, tolerability and pharmacokinetics of GSK286227, via single escalating intravenous doses, compared to a predecessor molecule, GSK1995057. After completion of Part 1 an interim data review will occur which will assess key comparability criteria to inform progression to Part 2 of the study. Part 2 of the study will involve single doses of GSK2862277 at a level predicted to be at or close to therapeutic dose levels. Part 2 will investigate both intravenous and inhaled routes of administration, in sequential manner, respectively. An interim data review will also occur after completion of Part 2, where all data accumulated previously will be assessed to examine appropriateness to progress to Part 3. Part 3 of the study will involve 5 days of repeat dosing via both inhaled and intravenous routes using the same dose administered in Part 2.

Conditions

Respiratory Disorders

Keywords

healthy volunteer; TNFR1; domain antibody; Lung injury

Outcome Measures

Primary Outcomes (13)

• Safety and tolerability of single IV or IH dose of GSK2862277 assessed by number of subjects with adverse events (AE)s in Part 1 and Part 2

  Safety and tolerability parameters will include recording of adverse events (AEs), throughout the study.

  Up to 42 days

• Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by number of subjects with AEs in Part 3

  Safety and tolerability parameters will include recording of AEs, throughout the study.

  Up to 42 days

• Safety and tolerability of single IV or IH dose of GSK2862277 assessed by laboratory tests in Part 1 and Part 2

  Laboratory tests will include haemogram, clinical chemistry, urine examination.

  Up to 42 days

• Safety and tolerability of repeat IV or IH dose of GSK2862277 as assessed by laboratory tests in Part 3

  Laboratory tests will include haemogram, clinical chemistry, urine examination.

  Up to 42 days

• Safety and tolerability of single IV or IH dose of GSK2862277 assessed by vital signs in Part 1 and Part 2

  Vital signs will include blood pressure (BP), heart rate respiration rate and body temperature.

  Up to 42 days

• Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by vital signs in Part 3

  Vital signs will include BP, heart rate respiration rate and body temperature.

  Up to 42 days

• Safety and tolerability of single IV or IH dose of GSK2862277 assessed by ECG in Part 1 and Part 2

  Safety data will include electrocardiogram (ECG) readings obtained at each timepoint during the study.

  Up to 42 days

• Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by ECG in Part 3

  Safety data will include ECG readings obtained at each timepoint during the study.

  Up to 42 days

• Safety and tolerability of single IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 1 and Part 2

  Spirometry monitoring will include forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).

  Up to 42 days

• Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 3

  Spirometry monitoring will include FEV1 and FVC.

  Up to 42 days

• Safety and tolerability of single IV dose of GSK2862277 as assessed by measurement of plasma cytokines in Part 1

  Blood samples will be collected for assessment of plasma cytokines.

  Up to 42 days

• Immunogenicity in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2

  Presence of anti GSK2862277 binding antibodies will be evaluated.

  Up to 60 days

• Immunogenicity in subjects receiving repeat IV or IH dose of GSK2862277 in Part 3

  Presence of anti GSK2862277 binding antibodies will be evaluated.

  Up to 60 days

Secondary Outcomes (8)

• Pharmacokinetic (PK) parameters in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2

  Up to 48 hours post dose

• PK parameters in subjects receiving repeat IV dose of GSK2862277 in Part 3 Cohort 3a

  Up to 48 hours post last dose

• PK parameters in subjects receiving repeat IH dose of GSK2862277 in Part 3 Cohort 3b

  Up to 48 hours post last dose

• PK parameters in subjects receiving single IV dose of GSK2862277 in Part 1

  Up to 48 hours post last dose

• Pharmacodynamic and immune function biomarkers in serum of subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2

  Up to 48 hours post last dose

Study Arms (11)

Part 1: Cohort 1a

EXPERIMENTAL

Single IV dose of GSK2862277 as a continuous infusion over 2 hours.

Drug: Single IV dose of GSK2862277

Part 1: Cohort 1b

EXPERIMENTAL

Single IV dose of GSK2862277 as a continuous infusion over 3 hours.

Drug: Single IV dose of GSK2862277

Part 1: Cohort 1c

EXPERIMENTAL

Single IV dose of GSK2862277 as a continuous infusion over 3 hours.

Drug: Single IV dose of GSK2862277

Part 2: Cohort 2a GSK2862277

EXPERIMENTAL

Single IV dose of GSK2862277 as a continuous infusion over 1 hour.

Drug: Single IV dose of GSK2862277

Part 2: Cohort 2a Placebo

EXPERIMENTAL

Matching placebo will be administered as a continuous IV infusion over 1 hour.

Drug: Matching placebo single dose IV infusion

Part 2: Cohort 2b GSK2862277

EXPERIMENTAL

Single IH dose of GSK2862277.

Drug: Single IH dose of GSK2862277

Part 2: Cohort 2b Placebo

EXPERIMENTAL

Matching placebo will be administered.

Drug: Matching placebo single dose IH

Part 3: Cohort 3a GSK2862277

EXPERIMENTAL

IV dose of GSK2862277 (decided from Part 2) as a continuous infusion over 1 hour for daily 5 days.

Drug: Repeat IV dose of GSK2862277

Part 3: Cohort 3a Placebo

EXPERIMENTAL

Matching placebo will be administered as IV infusion over 1 hour daily for 5 days.

Drug: Matching placebo repeat dose IV infusion

Part 3: Cohort 3b GSK2862277

EXPERIMENTAL

Repeat IH dose of GSK2862277 (decided from Part 2) daily for 5 days.

Drug: Repeat IH dose selected of GSK2862277 from Part 2

Part 3: Cohort 3b Placebo

EXPERIMENTAL

Matching placebo will be administered as IH daily for 5 days.

Drug: Matching placebo repeat dose IH

Interventions

Single IV dose of GSK2862277 DRUG

GSK2862277 solution available in a 40 mg vial for IV administration.

Part 1: Cohort 1a; Part 1: Cohort 1b; Part 1: Cohort 1c; Part 2: Cohort 2a GSK2862277

Matching placebo single dose IV infusion DRUG

Matching placebo solution available for IV administration.

Part 2: Cohort 2a Placebo

Single IH dose of GSK2862277 DRUG

GSK2862277 nebulised solution available in a 40 mg vial for IH administration.

Part 2: Cohort 2b GSK2862277

Matching placebo single dose IH DRUG

Matching placebo nebulised solution available for IH administration.

Part 2: Cohort 2b Placebo

Repeat IV dose of GSK2862277 DRUG

GSK2862277 solution available in a 40 mg vial for IV administration.

Part 3: Cohort 3a GSK2862277

Matching placebo repeat dose IV infusion DRUG

Matching placebo solution available for IV administration.

Part 3: Cohort 3a Placebo

Repeat IH dose selected of GSK2862277 from Part 2 DRUG

GSK2862277 nebulised solution available in a 40 mg vial for IH administration.

Part 3: Cohort 3b GSK2862277

Matching placebo repeat dose IH DRUG

Matching placebo nebulised solution available for IH administration.

Part 3: Cohort 3b 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:

• Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Subject is positive at screening for HAVH autoantibodies against GSK1995057 (Part 1 only).
• 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.
• A positive test for human immunodeficiency virus (HIV) antibody.
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

You may not qualify if:

• 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.
• A positive test for human immunodeficiency virus (HIV) antibody.
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Harrow, Middlesex, HA13UJ, United Kingdom

Location

Related Publications (1)

• Cordy JC, Morley PJ, Wright TJ, Birchler MA, Lewis AP, Emmins R, Chen YZ, Powley WM, Bareille PJ, Wilson R, Tonkyn J, Bayliffe AI, Lazaar AL. Specificity of human anti-variable heavy (VH ) chain autoantibodies and impact on the design and clinical testing of a VH domain antibody antagonist of tumour necrosis factor-alpha receptor 1. Clin Exp Immunol. 2015 Nov;182(2):139-48. doi: 10.1111/cei.12680. Epub 2015 Sep 11.

  PMID: 26178412 DERIVED

Related Links

• Results for study 116343 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Respiration Disorders; Lung Injury

Interventions

Infusions, Intravenous

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Lung Diseases; Thoracic Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Infusions, Parenteral

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 14, 2013
• First Posted: March 26, 2013
• Study Start: February 22, 2013
• Primary Completion: October 25, 2013
• Study Completion: October 25, 2013
• Last Updated: May 15, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)