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

NCT01899755 | Completed Phase 1

• 1 other identifier: 116987
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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).

Conditions

Psoriasis

Keywords

monoclonal antibody; healthy volunteer; TNF alpha

Outcome Measures

Primary Outcomes (8)

• Apparent systemic clearance (CL/F) of GSK2800528

  Up to Day 196

• Apparent systemic clearance (CL/F) of adalimumab

  Up to Day 140

• Adverse event (AE) and Serious Adverse event (SAE) reporting

  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

  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

  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

  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)

  Safety data for vital signs including blood pressure, heart rate, and body temperature will be measured

  Up to Day 196

• Electrocardiogram (ECG) monitoring

  Supine 12-lead ECG data will be monitored

  Up to Day 196

Secondary Outcomes (5)

• Plasma concentrations of GSK2800528 and derived pharmacokinetic parameters other than CL/F

  Up to Day 196

• Plasma concentrations of adalimumab and derived pharmacokinetic parameters other than CL/F

  Up to Day 140

• Incidence, titers, and specificity of anti-GSK2800528 antibodies.

  Up to Day 196

• Incidence, titers, and specificity of anti-adalimumab antibodies

  Up to Day 140

• Neutralising activity for samples with confirmed anti-drug antibodies

  Up to Day 196

Study Arms (3)

GSK2800528 Arm

EXPERIMENTAL

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

Placebo Arm

PLACEBO COMPARATOR

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

Adalimumab Arm

ACTIVE COMPARATOR

In Cohort 4, all subjects will receive adalimumab 40 mg (0.8 mL solution) as subcutaneous injection

Drug: Adalimumab, solution for injection

Interventions

GSK2800528, solution for injection DRUG

Drug will be administered at 3 different dose levels by subcutaneous injection.

GSK2800528 Arm

Placebo (0.9% w/v Sodium Chloride), solution for injection DRUG

Subcutaneous injection of. 0.8 mL solution will be administered

Placebo Arm

Adalimumab, solution for injection DRUG

Subcutaneous injection of 0.8 mL solution will be administered (40mg)

Adalimumab Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

Related Links

• Results for study 116987 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Psoriasis

Interventions

Solutions; Injections; Adalimumab

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2013
• First Posted: July 15, 2013
• Study Start: July 10, 2013
• Primary Completion: April 3, 2014
• Study Completion: April 3, 2014
• Last Updated: May 11, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)