Last updated: 11/07/2018 11:17:44
A study to evaluate the pharmacokinetics (PK), safety and tolerability, immunogenicity, and pharmacodynamics (PD) of GSK2800528 in healthy subjects.
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A study to evaluate the pharmacokinetics, safety and tolerability, immunogenicity, and pharmacodynamics of GSK2800528 in healthy subjects.
Trial description: 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).
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Apparent systemic clearance (CL/F) of GSK2800528
Timeframe: Up to Day 196
Apparent systemic clearance (CL/F) of adalimumab
Timeframe: Up to Day 140
Adverse event (AE) and Serious Adverse event (SAE) reporting
Timeframe: Up to Day 196
Laboratory safety assessment for clinical chemistry parameters
Timeframe: Up to Day 196
Laboratory safety assessment for hematology parameters
Timeframe: Up to Day 196
Laboratory safety assessment for urinalysis parameters
Timeframe: Up to Day 196
Vital signs monitoring (blood pressure, heart rate, body temperature)
Timeframe: Up to Day 196
Electrocardiogram (ECG) monitoring
Timeframe: Up to Day 196
Secondary outcomes:
Plasma concentrations of GSK2800528 and derived pharmacokinetic parameters other than CL/F
Timeframe: Up to Day 196
Plasma concentrations of adalimumab and derived pharmacokinetic parameters other than CL/F
Timeframe: Up to Day 140
Incidence, titers, and specificity of anti-GSK2800528 antibodies.
Timeframe: Up to Day 196
Incidence, titers, and specificity of anti-adalimumab antibodies
Timeframe: Up to Day 140
Neutralising activity for samples with confirmed anti-drug antibodies
Timeframe: Up to Day 196
Interventions:
Drug: GSK2800528, solution for injection
Drug: Placebo (0.9% w/v Sodium Chloride), solution for injection
Drug: Adalimumab, solution for injection
Enrollment:
45
Observational study model:
Not applicable
Primary completion date:
2014-03-04
Time perspective:
Not applicable
Clinical publications:
Iain McSherry, Stefano Zamuner, Tarjinder Sahota, Carol Routledge , Katherine Davy, Mary Birchler, Juliet Reid, Bams Abila, Malcolm Boyce, Bettina Cortezi. Safety, Pharmacokinetics, Pharmacodynamics and Immunogenicity of a new anti-TNFa mAb (GSK2800528). Intrinsic Activity. 2015;3(Suppl. 2):A3.2.
Medical condition
Psoriasis
Product
GSK2800528, adalimumab
Collaborators
Not applicable
Study date(s)
July 2013 to April 2014
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 65 years
Accepts healthy volunteers
Yes
- 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.
- 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).
Inclusion and exclusion criteria
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.
Trial location(s)
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
2014-03-04
Actual study completion date
2014-03-04
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 116987 can be found on the GSK Clinical Study Register.
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