A Study to Evaluate the Pharmacokinetics (PK), Safety and Tolerability, Immunogenicity, and Pharmacodynamics (PD) of GSK2800528 in Healthy Subjects.

May 10, 2017 updated by: GlaxoSmithKline

A Study to Evaluate the Pharmacokinetics, Safety and Tolerability, Immunogenicity, and Pharmacodynamics of GSK2800528 in Healthy Subjects.

GSK2800528 is being developed as a human anti-tumor necrosis factor (TNF) alpha monoclonal antibody (mAb) for the treatment of immune-inflammatory diseases. The study will be conducted in healthy volunteers and divided into 4 cohorts. Cohorts 1 to 3 will consist of groups of 12 subjects, 9 on active treatment (GSK2800528), and 3 on placebo. Cohort 4 will consist of a group of 9 subjects, all on active treatment (adalimumab).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
45

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, NW10 7EW
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • ALT, alkaline phosphatase and bilirubin <= 1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Average bazett's corrected QT interval (QTcB) < 450 msec, or QTcB < 480 msec in subjects with Bundle Branch Block.
  • 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 at the investigator's discretion provided the finding is unlikely to introduce additional risk factors, jeopardize study integrity, or to interfere with the study procedures.
  • Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • A female subject is eligible to participate if she is of: non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 21.7 international unit/liter (IU/L) and oestradiol <110 picomoles/liter (pmol/L) is confirmatory. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods specified in study protocol.
  • Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods specified in study protocol.
  • Body weight >= 60 kg and body mass index (BMI) within the range 19 to 31 kilogram/meter2 (kg/m2) (inclusive).

Exclusion Criteria:

  • A positive pre-study Quantiferon test, Hepatitis B surface antigen, or positive Hepatitis C antibody result within 3 months of screening.
  • Current or chronic history of liver or kidney disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • A positive pre-study drug/alcohol screen.
  • A positive test for human immunodeficiency virus (HIV) antibody.
  • Previous treatment with adalimumab.
  • Current, or history of, cancer.
  • 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 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • 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: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Travel to regions of high endemic tuberculosis/infection, as judged by the investigator or medical monitor, is prohibited from the start of screening until the final follow up visit.
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • 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.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Subject is mentally or legally incapacitated.
  • Current evidence or history of bacterial, viral, or fungal infection within 7 days before dosing.
  • Subject has received any type of vaccination within 21 days before dosing or will require vaccination prior to the end of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: GSK2800528 Arm
Subjects will be assigned to treatments in accordance with the randomization schedule in Cohorts 1 to 3. Treatments will be randomized with placebo in a 3:1 ratio. The final randomization code will also pre-define the sentinel subjects to ensure that of the first two subjects in each cohort, one will receive GSK2800528 and the other will receive placebo.
Drug: GSK2800528, solution for injection
Drug will be administered at 3 different dose levels by subcutaneous injection.
PLACEBO_COMPARATOR: Placebo Arm
Subjects will be assigned to treatments in accordance with the randomization schedule in Cohorts 1 to 3. Treatments will be randomized with placebo in a 3:1 ratio. The final randomization code will also pre-define the sentinel subjects to ensure that of the first two subjects in each cohort, one will receive GSK2800528 and the other will receive placebo.
Drug: Placebo (0.9% w/v Sodium Chloride), solution for injection
Subcutaneous injection of. 0.8 mL solution will be administered
ACTIVE_COMPARATOR: Adalimumab Arm
In Cohort 4, all subjects will receive adalimumab 40 mg (0.8 mL solution) as subcutaneous injection
Drug: Adalimumab, solution for injection
Subcutaneous injection of 0.8 mL solution will be administered (40mg)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Apparent systemic clearance (CL/F) of GSK2800528
Time Frame: Up to Day 196
Up to Day 196
Apparent systemic clearance (CL/F) of adalimumab
Time Frame: Up to Day 140
Up to Day 140
Adverse event (AE) and Serious Adverse event (SAE) reporting
Time Frame: Up to Day 196
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. An SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function.
Up to Day 196
Laboratory safety assessment for clinical chemistry parameters
Time Frame: Up to Day 196
Safety data for laboratory clinical chemistry parameters including albumin, creatinine, glucose, sodium, potassium, chloride, calcium, total protein, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatise, total and direct bilirubin, and uric acid will be assessed
Up to Day 196
Laboratory safety assessment for hematology parameters
Time Frame: Up to Day 196
Safety data for laboratory hematology parameters including platelet count, red blood cell (RBC) count, absolute white blood cell (WBC) count, reticulocyte count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), mean corpuscular haemoglobin (MCH), neutrophils, lymphocytes, monocytes, eosinophils, and basophils will be assessed.
Up to Day 196
Laboratory safety assessment for urinalysis parameters
Time Frame: Up to Day 196
Safety data for laboratory urinalysis parameters including specific gravity, pH, glucose, protein, blood and ketones by dipstick , and microscopic examination will be assessed
Up to Day 196
Vital signs monitoring (blood pressure, heart rate, body temperature)
Time Frame: Up to Day 196
Safety data for vital signs including blood pressure, heart rate, and body temperature will be measured
Up to Day 196
Electrocardiogram (ECG) monitoring
Time Frame: Up to Day 196
Supine 12-lead ECG data will be monitored
Up to Day 196

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Plasma concentrations of GSK2800528 and derived pharmacokinetic parameters other than CL/F
Time Frame: Up to Day 196
Blood samples for PK analysis of GSK2800528 will be collected to assess plasma concentration and derived PK parameters including maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration time curve [AUC(0-t) and AUC(0-infinity)], and apparent terminal phase half-life (t1/2)
Up to Day 196
Plasma concentrations of adalimumab and derived pharmacokinetic parameters other than CL/F
Time Frame: Up to Day 140
Blood samples for PK analysis of adalimumab will be collected to assess plasma concentration and derived PK parameters including Cmax, tmax, AUC(0-t) and AUC(0-infinity), and t1/2
Up to Day 140
Incidence, titers, and specificity of anti-GSK2800528 antibodies.
Time Frame: Up to Day 196
Up to Day 196
Incidence, titers, and specificity of anti-adalimumab antibodies
Time Frame: Up to Day 140
Up to Day 140
Neutralising activity for samples with confirmed anti-drug antibodies
Time Frame: Up to Day 196
Up to Day 196

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 10, 2013

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 3, 2014

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 3, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 11, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 11, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 15, 2013

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 11, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 10, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 116987

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

Study Data/Documents

  1. Dataset Specification
    Information identifier: 116987
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  2. Annotated Case Report Form
    Information identifier: 116987
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  3. Informed Consent Form
    Information identifier: 116987
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  4. Individual Participant Data Set
    Information identifier: 116987
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  5. Statistical Analysis Plan
    Information identifier: 116987
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  6. Study Protocol
    Information identifier: 116987
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  7. Clinical Study Report
    Information identifier: 116987
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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