A Phase I Rheumatoid Arthritis Study in Healthy Volunteers

NCT00539760 | Completed Phase 1

• 1 other identifier: 110394
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

GSK182771 is a domain antibody targeting the interleukin (IL)-1 receptor which is being developed for the treatment of rheumatoid arthritis. This study is being done in healthy volunteers to verify the safety and tolerability of GSK182771

Conditions

Arthritis, Rheumatoid

Keywords

domain antibody; Rheumatoid Arthritis,

Outcome Measures

Primary Outcomes (9)

• Number of subjects with abnormal clinical chemistry findings

  Blood samples will be collected at specific time points as a measure of safety

  Up to 29 days

• Number of subjects with abnormal clinical hematology findings

  Blood samples will be collected at specific time points as a measure of safety

  Up to 29 days

• Number of subjects with abnormal urinalysis findings

  Urine samples will be collected at specific time points as a measure of safety

  Up to 29 days

• Number of subjects with abnormal blood pressure values

  Systolic and diastolic blood pressure will be measured in a supine position after at least 5 minutes of rest as a measure of safety.

  Up to 29 days

• Number of subjects with abnormal heart rate values

  Heart rate will be measured in a supine position after at least 5 minutes of rest as a measure of safety.

  Up to 29 days

• Number of subjects with abnormal respiratory rate values

  Respiratory rate will be measured in a supine position after at least 5 minutes of rest as a measure of safety.

  Up to 29 days

• Number of subjects with abnormal body temperature findings

  Body temperature will be measured in a supine position after at least 5 minutes of rest as a measure of safety.

  Up to 29 days

• Number of subjects with abnormal electrocardiogram (ECG) findings

  12-lead ECG measurements will be performed in a supine position after at least 5 minutes of rest as a measure of safety

  Up to 29 days

• Number of subjects with adverse events (AEs)

  An adverse event 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.

  Up to 29 days

Secondary Outcomes (11)

• Plasma concentrations of GSK1827771

  Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28

• Maximum plasma concentration (Cmax) of GSK1827771

  Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28

• Area under the curve (AUC) of GSK1827771

  Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28

• Frequency of anti-GSK1827771

  Up to 29 days

• Titer of anti-GSK1827771

  Up to 29 days

Study Arms (6)

Subjects receiving GSK 1827771 in sub-cohort Xa (Cohort 1-5)

EXPERIMENTAL

Eligible subjects will receive GSK1827771 with the starting dose of 0.3 milligram (mg)

Drug: GSK1827771

Subjects receiving placebo in sub-cohort Xa (Cohort 1-5)

PLACEBO COMPARATOR

Eligible subjects will receive placebo matching to GSK1827771

Drug: Placebo

Subjects receiving GSK 1827771 in sub-cohort Xb (Cohort 1-5)

EXPERIMENTAL

Eligible subjects will receive GSK1827771 via injection

Drug: GSK1827771

Subjects receiving placebo in sub-cohort Xb (Cohort 1-5)

PLACEBO COMPARATOR

Eligible subjects will receive placebo matching to GSK1827771

Drug: Placebo

Subjects receiving GSK 1827771 in sub-cohort Xc (Cohort 1-5)

EXPERIMENTAL

Eligible subjects will receive GSK1827771 via injection

Drug: GSK1827771

Subjects receiving placebo in sub-cohort Xc (Cohort 1-5)

PLACEBO COMPARATOR

Eligible subjects will receive placebo matching to GSK1827771

Drug: Placebo

Interventions

GSK1827771 DRUG

GSK1827771 will be administered using injection via subcutaneous (SC) route.

Subjects receiving GSK 1827771 in sub-cohort Xa (Cohort 1-5); Subjects receiving GSK 1827771 in sub-cohort Xb (Cohort 1-5); Subjects receiving GSK 1827771 in sub-cohort Xc (Cohort 1-5)

Placebo DRUG

Placebo to GSK1827771 for Injection will be administered via SC route

Subjects receiving placebo in sub-cohort Xa (Cohort 1-5); Subjects receiving placebo in sub-cohort Xb (Cohort 1-5); Subjects receiving placebo in sub-cohort Xc (Cohort 1-5)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult men or women as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests and cardiac assessment.
• Female subjects of non-childbearing potential.
• Male subjects must agree to abstain from or agree to use adequate contraception, in addition to having their female partner use another form of contraception. This criterion must be followed from the time of the first dose of study medication until Pharmacokinetic levels are determined to be below the LLQ.
• Men or women who are between 18 and 55 years of age, inclusive.
• Body Mass Index (BMI) within the range of 18-35 kilogram per meter square (kg/m\^2) inclusive.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

You may not qualify if:

• The subject has a positive pre-study urine drug/urine alcohol screen. A minimum list of drugs that will be screened for includes amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
• A history of regular alcohol consumption averaging \>7 drinks/week for females or \>14 drinks/week for males. One drink is equivalent to (12 g alcohol) = 5 ounces \[150 milliliter (mL)\] of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of 80 proof distilled spirits
• The subject is unwilling to abstain from alcohol consumption from 48 hour prior to dosing until discharge from the clinic, and for 48 hour prior to all other out-patient clinic visits.
• Smoked or used tobacco or nicotine-containing products within the previous 6 months prior to the first dose of current study medication.
• The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
• Previous exposure to or treatment with PEGylated molecules.
• Use of anti-Tumor Necrosis Factor (anti-TNF) drugs within 60 days prior to dosing.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days , 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 (including antibiotics) which, in the opinion of the investigator and/or GSK Medical Monitor, contraindicates the subject's participation.
• Positive pregnancy test at Screening or on Day -1 (females only).
• Any clinically significant abnormality identified on the screening medical assessment or examination, or ECG.
• Any white blood cell (WBC) or neutrophil count outside the normal range at screening or on Day -1.
• History of significant cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions that in the opinion of the investigator and/or GSK Medical Monitor, places the subject at an unacceptable risk as participant in this trial.
• History of any autoimmune or current inflammatory conditions including rheumatoid arthritis or any other joint disease.
• History of malignancy, except for surgically cured basal cell carcinoma or cured cervical carcinoma (\> 2 yrs prior to dosing).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Evansville, Indiana, 47714, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: October 4, 2007
• First Posted: October 5, 2007
• Study Start: September 5, 2007
• Primary Completion: April 5, 2008
• Study Completion: April 5, 2008
• Last Updated: August 15, 2017

Record last verified: 2017-08

Locations

US (2)