Back to results

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

Primary Purpose

Respiratory Disorders

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Single IV dose of GSK2862277

Matching placebo single dose IV infusion

Single IH dose of GSK2862277

Matching placebo single dose IH

Repeat IV dose of GSK2862277

Matching placebo repeat dose IV infusion

Repeat IH dose selected of GSK2862277 from Part 2

Matching placebo repeat dose IH

About this trial

This is an interventional treatment trial for Respiratory Disorders focused on measuring healthy volunteer, TNFR1, domain antibody, Lung injury

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm Type

Experimental

Arm Label

Part 1: Cohort 1a

Part 1: Cohort 1b

Part 1: Cohort 1c

Part 2: Cohort 2a GSK2862277

Part 2: Cohort 2a Placebo

Part 2: Cohort 2b GSK2862277

Part 2: Cohort 2b Placebo

Part 3: Cohort 3a GSK2862277

Part 3: Cohort 3a Placebo

Part 3: Cohort 3b GSK2862277

Part 3: Cohort 3b Placebo

Arm Description

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

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

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

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

Single IH dose of GSK2862277.

Matching placebo will be administered.

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

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

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

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

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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

Presence of anti GSK2862277 binding antibodies will be evaluated.

Secondary Outcome Measures

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

The blood samples will be collected for plasma concentrations of GSK2862277.

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

The blood samples will be collected for plasma concentrations of GSK2862277.

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

The blood samples will be collected for plasma concentrations of GSK2862277

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

The PK parameters will be compared with historic GSK1995057 PK data in Part 1

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

The pharmacodynamic and immune function biomarkers in serum.

Pharmacodynamic and immune function biomarkers in serum of subjects receiving repeat IV or IH dose of GSK2862277in Part 3

The pharmacodynamic and immune function biomarkers in serum.

Change from baseline in IL-8 expression in ex vivo WBA in subjects receiving single IV 0.05 mg/kg dose of GSK2862277 in Part 1 in Cohort1c

IL-8 expression in ex vivo whole blood essay (WBA).

Composite of urine parameters in subjects receiving single IV 2 mg/kg dose of GSK2862277 in Part 2 in Cohort 2a

The urine samples will be collected for urine concentrations of GSK2862277.

Full Information

NCT ID

NCT01818024

First Posted

February 14, 2013

Last Updated

May 12, 2017

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT01818024

Brief Title

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

Official Title

A Three Part, Randomised, Placebo-controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of Inhaled and Intravenous GSK2862277 in Healthy Volunteers

Study Type

Interventional

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Completed

Study Start Date

February 22, 2013 (Actual)

Primary Completion Date

October 25, 2013 (Actual)

Study Completion Date

October 25, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Respiratory Disorders

Keywords

healthy volunteer, TNFR1, domain antibody, Lung injury

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

Participant

Allocation

Randomized

Enrollment

54 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Cohort 1a

Arm Type

Experimental

Arm Description

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

Arm Title

Part 1: Cohort 1b

Arm Type

Experimental

Arm Description

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

Arm Title

Part 1: Cohort 1c

Arm Type

Experimental

Arm Description

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

Arm Title

Part 2: Cohort 2a GSK2862277

Arm Type

Experimental

Arm Description

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

Arm Title

Part 2: Cohort 2a Placebo

Arm Type

Experimental

Arm Description

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

Arm Title

Part 2: Cohort 2b GSK2862277

Arm Type

Experimental

Arm Description

Single IH dose of GSK2862277.

Arm Title

Part 2: Cohort 2b Placebo

Arm Type

Experimental

Arm Description

Matching placebo will be administered.

Arm Title

Part 3: Cohort 3a GSK2862277

Arm Type

Experimental

Arm Description

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

Arm Title

Part 3: Cohort 3a Placebo

Arm Type

Experimental

Arm Description

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

Arm Title

Part 3: Cohort 3b GSK2862277

Arm Type

Experimental

Arm Description

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

Arm Title

Part 3: Cohort 3b Placebo

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Single IV dose of GSK2862277

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Matching placebo single dose IV infusion

Intervention Description

Matching placebo solution available for IV administration.

Intervention Type

Drug

Intervention Name(s)

Single IH dose of GSK2862277

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Matching placebo single dose IH

Intervention Description

Matching placebo nebulised solution available for IH administration.

Intervention Type

Drug

Intervention Name(s)

Repeat IV dose of GSK2862277

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Matching placebo repeat dose IV infusion

Intervention Description

Matching placebo solution available for IV administration.

Intervention Type

Drug

Intervention Name(s)

Repeat IH dose selected of GSK2862277 from Part 2

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Matching placebo repeat dose IH

Intervention Description

Matching placebo nebulised solution available for IH administration.

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

Up to 42 days

Title

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

Description

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

Time Frame

Up to 42 days

Title

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

Description

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

Time Frame

Up to 42 days

Title

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

Description

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

Time Frame

Up to 42 days

Title

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

Description

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

Time Frame

Up to 42 days

Title

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

Description

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

Time Frame

Up to 42 days

Title

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

Description

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

Time Frame

Up to 42 days

Title

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

Description

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

Time Frame

Up to 42 days

Title

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

Description

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

Time Frame

Up to 42 days

Title

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

Description

Spirometry monitoring will include FEV1 and FVC.

Time Frame

Up to 42 days

Title

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

Description

Blood samples will be collected for assessment of plasma cytokines.

Time Frame

Up to 42 days

Title

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

Description

Presence of anti GSK2862277 binding antibodies will be evaluated.

Time Frame

Up to 60 days

Title

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

Description

Presence of anti GSK2862277 binding antibodies will be evaluated.

Time Frame

Up to 60 days

Secondary Outcome Measure Information:

Title

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

Description

The blood samples will be collected for plasma concentrations of GSK2862277.

Time Frame

Up to 48 hours post dose

Title

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

Description

The blood samples will be collected for plasma concentrations of GSK2862277.

Time Frame

Up to 48 hours post last dose

Title

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

Description

The blood samples will be collected for plasma concentrations of GSK2862277

Time Frame

Up to 48 hours post last dose

Title

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

Description

The PK parameters will be compared with historic GSK1995057 PK data in Part 1

Time Frame

Up to 48 hours post last dose

Title

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

Description

The pharmacodynamic and immune function biomarkers in serum.

Time Frame

Up to 48 hours post last dose

Title

Pharmacodynamic and immune function biomarkers in serum of subjects receiving repeat IV or IH dose of GSK2862277in Part 3

Description

The pharmacodynamic and immune function biomarkers in serum.

Time Frame

Up to 48 hours post last dose

Title

Change from baseline in IL-8 expression in ex vivo WBA in subjects receiving single IV 0.05 mg/kg dose of GSK2862277 in Part 1 in Cohort1c

Description

IL-8 expression in ex vivo whole blood essay (WBA).

Time Frame

Up to 12 hours post dose

Title

Composite of urine parameters in subjects receiving single IV 2 mg/kg dose of GSK2862277 in Part 2 in Cohort 2a

Description

The urine samples will be collected for urine concentrations of GSK2862277.

Time Frame

Up to 48 hours post dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Harrow

State/Province

Middlesex

ZIP/Postal Code

HA13UJ

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Citations:

PubMed Identifier

26178412

Citation

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.

Results Reference

derived

Links:

URL

https://www.clinicalstudydatarequest.com

Description

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Available IPD and Supporting Information:

Available IPD/Information Type

Dataset Specification

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

116343

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Individual Participant Data Set

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

116343

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Clinical Study Report

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

116343

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Annotated Case Report Form

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

116343

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Informed Consent Form

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

116343

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Statistical Analysis Plan

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

116343

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Study Protocol

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

116343

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Learn more about this trial

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

We'll reach out to this number within 24 hrs