Clinical trial NCT01899755: A Study to Evaluate the Pharmacokinetics (PK), Safety and Tolerability, Immunogenicity, and Pharmacodynamics (PD) of GSK2800528 in Healthy Subjects.
Official title: A Study to Evaluate the Pharmacokinetics, Safety and Tolerability, Immunogenicity, and Pharmacodynamics of GSK2800528 in Healthy Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Psoriasis
Keywords: monoclonal antibody
healthy volunteer
TNF alpha
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-07-15
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility 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.

Primary outcomes:
measure: Apparent systemic clearance (CL/F) of GSK2800528
timeFrame: Up to Day 196
measure: Apparent systemic clearance (CL/F) of adalimumab
timeFrame: Up to Day 140
measure: Adverse event (AE) and Serious Adverse event (SAE) reporting
timeFrame: Up to Day 196
measure: Laboratory safety assessment for clinical chemistry parameters
timeFrame: Up to Day 196
measure: Laboratory safety assessment for hematology parameters
timeFrame: Up to Day 196
measure: Laboratory safety assessment for urinalysis parameters
timeFrame: Up to Day 196
measure: Vital signs monitoring (blood pressure, heart rate, body temperature)
timeFrame: Up to Day 196
measure: Electrocardiogram (ECG) monitoring
timeFrame: Up to Day 196
Secondary outcomes:
measure: Plasma concentrations of GSK2800528 and derived pharmacokinetic parameters other than CL/F
timeFrame: Up to Day 196
measure: Plasma concentrations of adalimumab and derived pharmacokinetic parameters other than CL/F
timeFrame: Up to Day 140
measure: Incidence, titers, and specificity of anti-GSK2800528 antibodies.
timeFrame: Up to Day 196
measure: Incidence, titers, and specificity of anti-adalimumab antibodies
timeFrame: Up to Day 140
measure: Neutralising activity for samples with confirmed anti-drug antibodies
timeFrame: Up to Day 196
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: