A Factorial-design, Randomised, Double-blind, Placebo-controlled, Dose Optimisation Study to Investigate the Safety, Efficacy, Immunogenicity and Pharmacokinetics of ART621 Following Multiple Dose Administration in Subjects Diagnosed With Rheumatoid Arthritis Concomitantly Taking Methotrexate
Overview
- Phase
- Phase 2
- Intervention
- ART621
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Arana Therapeutics Ltd
- Enrollment
- 27
- Locations
- 1
- Primary Endpoint
- Safety and tolerability of subcutaneous injections of ART621 (preceded by a single i.v. loading dose) at different dose frequencies
- Status
- Completed
- Last Updated
- 16 years ago
Overview
Brief Summary
The purpose of this clinical trial is to establish what dose level and dosing frequency is optimal in the treatment of rheumatoid arthritis patients with ART621.
Detailed Description
Despite being effective in approximately 60% of subjects, there are limitations to existing anti-TNF therapies especially in relation to immunogenicity, safety and administration. In addition, due to their high molecular weight, currently marketed products are largely confined to the blood stream. ART621 is an anti-TNF molecule that contains 2 identical domain "antibodies" that have the binding activity of a full antibody but with a substantially smaller molecular size. The molecular weight of approximately half that of full size antibodies is predicted to, a) have improved tissue penetration and, b) to be less immunogenic than full size antibodies. This clinical trial is designed to establish the optimal dose level and dose frequency of ART621 in the treatment of patients with rheumatoid arthritis and to obtain data relating to the safety, immunogenicity and pharmacokinetics of ART621 when administered with an intravenous loading dose followed by subcutaneous administration every week compared to every fortnight.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients who are willing to give signed informed consent..
- •Male or female subjects at least 18 years of age and no more than 80 years of age.
- •Women of childbearing potential, or men of reproductive potential, must be using adequate (in the investigator's opinion) birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilisation) during the study. Female subjects of childbearing potential must test negative for pregnancy prior to enrolling in the study. Post menopausal (cessation of menses for more than 2 years) women are eligible for this study.
- •Diagnosis of RA according to the revised (1987) American College of Rheumatology criteria for at least 6 months prior to screening.
- •Meet ACR functional class criteria I, II or III.
- •Have active RA at the time of screening and at baseline, defined as ≥ 6 swollen joints and ≥ 6 tender joints (from 68 joint count) together with at least 2 of the following 3 criteria:
- •CRP level ≥ 1.5 mg/dl;
- •ESR by Westergren method ≥ 28 mm in the first hour; or
- •morning stiffness ≥ 45 minutes.
- •At least one of the following should be present at screening:
Exclusion Criteria
- •Body weight \>98 kg.
- •Pregnant, nursing, or planning a pregnancy (both men and women) within 9 months of enrolment.
- •Screening laboratory tests:
- •haemoglobin ≤ 8.0 gm/dl
- •white blood cells ≤ 3.0 x103 cells/µl
- •neutrophils ≤ 1.5 x 103 cells/µl
- •platelets ≤100 x 103 cells/µl
- •serum transaminase level (AST and ALT) ≥ 2 times upper limit of normal (ULN)
- •serum creatinine ≥ 0.15 mmol/l
- •Subjects with a diagnosis of juvenile arthritis or other inflammatory or autoimmune diseases that might confound the evaluations of benefit from ART621 such as ankylosing spondylitis, systemic lupus erythematosus and Lyme disease.
Arms & Interventions
1
Intervention: ART621
2
Intervention: ART621
3
Intervention: ART621
4
Intervention: ART621
5
Intervention: Placebo
6
Intervention: Placebo
Outcomes
Primary Outcomes
Safety and tolerability of subcutaneous injections of ART621 (preceded by a single i.v. loading dose) at different dose frequencies
Time Frame: 3 months