AzTrials
AzTrials

Respiratory DisordersPhase 1NCT01818024

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

A Phase 1 study testing Single IV dose of GSK2862277, Single IH dose of GSK2862277 and Repeat IV dose of GSK2862277 in people with Respiratory Disorders, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Respiratory Disorders
What is being tested?
Single IV dose of GSK2862277, Single IH dose of GSK2862277 and Repeat IV dose of GSK2862277
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
54 participants
Where
1 siteUnited Kingdom
Study dates
22 Feb 2013to 25 Oct 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site
  • GSK Investigational Site

    Harrow, Middlesex, HA13UJ

Other trials in United Kingdom

About this study

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

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.

Read more

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.

Being tested
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
Keywords
healthy volunteer, TNFR1, domain antibody, Lung injury
Medical subject headings
Respiration Disorders, Lung Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Single IV dose of GSK2862277Drug

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

  • Matching placebo single dose IV infusionDrug

    Matching placebo solution available for IV administration.

  • Single IH dose of GSK2862277Drug

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

  • Matching placebo single dose IHDrug

    Matching placebo nebulised solution available for IH administration.

  • Repeat IV dose of GSK2862277Drug

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

  • Matching placebo repeat dose IV infusionDrug

    Matching placebo solution available for IV administration.

  • Repeat IH dose selected of GSK2862277 from Part 2Drug

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

  • Matching placebo repeat dose IHDrug

    Matching placebo nebulised solution available for IH administration.

Study groups in NCT01818024
Study groupRoleWhat they receive
Part 1: Cohort 1aExperimentalSingle IV dose of GSK2862277 as a continuous infusion over 2 hours.
Receives: Drug: Single IV dose of GSK2862277
Part 1: Cohort 1bExperimentalSingle IV dose of GSK2862277 as a continuous infusion over 3 hours.
Receives: Drug: Single IV dose of GSK2862277
Part 1: Cohort 1cExperimentalSingle IV dose of GSK2862277 as a continuous infusion over 3 hours.
Receives: Drug: Single IV dose of GSK2862277
Part 2: Cohort 2a GSK2862277ExperimentalSingle IV dose of GSK2862277 as a continuous infusion over 1 hour.
Receives: Drug: Single IV dose of GSK2862277
Part 2: Cohort 2a PlaceboExperimentalMatching placebo will be administered as a continuous IV infusion over 1 hour.
Receives: Drug: Matching placebo single dose IV infusion
Part 2: Cohort 2b GSK2862277ExperimentalSingle IH dose of GSK2862277.
Receives: Drug: Single IH dose of GSK2862277
Part 2: Cohort 2b PlaceboExperimentalMatching placebo will be administered.
Receives: Drug: Matching placebo single dose IH
Part 3: Cohort 3a GSK2862277ExperimentalIV dose of GSK2862277 (decided from Part 2) as a continuous infusion over 1 hour for daily 5 days.
Receives: Drug: Repeat IV dose of GSK2862277
Part 3: Cohort 3a PlaceboExperimentalMatching placebo will be administered as IV infusion over 1 hour daily for 5 days.
Receives: Drug: Matching placebo repeat dose IV infusion
Part 3: Cohort 3b GSK2862277ExperimentalRepeat IH dose of GSK2862277 (decided from Part 2) daily for 5 days.
Receives: Drug: Repeat IH dose selected of GSK2862277 from Part 2
Part 3: Cohort 3b PlaceboExperimentalMatching placebo will be administered as IH daily for 5 days.
Receives: Drug: Matching placebo repeat dose IH

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 42 days

  2. 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.

    Measured: Up to 42 days

  3. 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.

    Measured: Up to 42 days

  4. 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.

    Measured: Up to 42 days

  5. 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.

    Measured: Up to 42 days

  6. 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.

    Measured: Up to 42 days

  7. 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.

    Measured: Up to 42 days

  8. 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.

    Measured: Up to 42 days

  9. 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).

    Measured: Up to 42 days

  10. 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.

    Measured: Up to 42 days

  11. 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.

    Measured: Up to 42 days

  12. 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.

    Measured: Up to 60 days

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

    Presence of anti GSK2862277 binding antibodies will be evaluated.

    Measured: Up to 60 days

Secondary outcomes (8)
  1. 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.

    Measured: Up to 48 hours post dose

  2. 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.

    Measured: Up to 48 hours post last dose

  3. 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

    Measured: Up to 48 hours post last dose

  4. 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

    Measured: Up to 48 hours post last dose

  5. 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.

    Measured: Up to 48 hours post last dose

  6. 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.

    Measured: Up to 48 hours post last dose

  7. 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).

    Measured: Up to 12 hours post dose

  8. 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.

    Measured: Up to 48 hours post dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Mar 2013 (estimated)
  2. Study start22 Feb 2013
  3. Primary completion25 Oct 2013
  4. Study completion25 Oct 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
Single blind
Who is masked
Participant
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01818024
Sponsor's protocol ID
116343
Status last verified
May 2017
First submitted
14 Feb 2013
Last updated
15 May 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • 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.

    PubMed 26178412

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Single IV dose of GSK2862277, Single IH dose of GSK2862277 and Repeat IV dose of GSK2862277 in people with Respiratory Disorders, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Up to 42 days). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01818024, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2017.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in