Rheumatoid arthritis MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Code: ART621
Pharmaceutical Form: Solution for injection
Current Sponsor code: ART621
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Phar
Sponsors
Arana Therapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Valid written informed consent. 2. Male or female subjects = 18 and = 80 years old. 3. Women of childbearing potential, or men of fathering potential, must be using adequate birth control measures during the study. Female subjects of childbearing potential must test negative for pregnancy prior to enrolling in the study. Post menopausal women are eligible for this study. 4. Diagnosis of RA for at least 6 months and no longer than 3 years prior to screening. 5. Meet ACR functional class criteria I, II or III. 6. 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. 7. At least one should be present at screening: -documented history or current presence of positive rheumatoid factor; - presence of serum anti-CCP antibodies; or screening radiographic erosion. 8. Have been tolerating concomitant methotrexate (oral or subcutaneous) for at least 3 months prior to screening and on a stable dose between 10-25 mg per week for at least 6 weeks prior to the first study dose. The route of administration must also be stable. Use of methotrexate dose of 25-50 mg every 2 weeks is also acceptable. (Other DMARDs taken concomitantly with methotrexate are not allowed. Those subjects concomitantly receiving additional DMARDs with methotrexate may enter the study by stopping the additional DMARD at least 4 weeks prior to first study dose). 9. If using the following medication, the subject must be on a stable dose for the 4 weeks prior to the first study dose and maintain that dose throughout the study: -oral corticosteroids, equivalent to = 10 mg of prednisone/day. -one nonsteroidal anti-inflammatory drug (NSAID). -3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) or fibrates (see Protocol Section 7.1 for acceptable doses). 10. Does not have active or latent TB according to eligibility assessment and screening rules 11. Is willing and able to comply with study visits and other protocol requirements. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Pregnant, nursing, or planning a pregnancy (both men and women) within 9 months of enrolment. 2. Subjects weighing > 100 kgs. 3. Screening laboratory tests: -hemoglobin = 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 4. Subjects with 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. 5. Subjects who have previously failed to respond to any oral or injectable anti-TNFa therapy or subjects who have had to stop anti-TNFa therapy for safety reasons. Subjects who have successfully responded to anti-TNF therapy in the past (but discontinued for reasons other than safety or lack of efficacy) > 6 months prior to study day one may enrol. Patients who have participated in a previous anti-TNF therapy study are eligible if they are confirmed to have received placebo. 6. Subjects who have previously received the following anti-rheumatic drugs: interleukin-1 receptor antagonist [anakinra], rituximab, anti-CD4 antibody, abatacept, thalidomide, p38 MAP kinase inhibitor and other agents. 7. Subjects who have undergone plasmapheresis within 6 months prior to randomisation. 8. Have received intraarticular, intramuscular, or intravenous corticosteroids, including intramuscular adrenocorticotropic hormone, during the 4 weeks prior to the first study dose, or non-stable doses of oral steroids. 9. Subjects with a history of any clinically significant adverse reaction to murine or chimeric proteins, including serious allergic reactions. 10. Subjects with Felty’s syndrome or a history of Felty’s syndrome. 11. Subjects who have received or are expecting to receive any live virus or bacterial vaccinations within 1 month before first study dose, during the study, or up to 3 months after the study dose. 12. Subjects with a history of, presence of, or at high risk of serious infection including: -history of active TB, or positive Mantoux test or QuantiFERON Gold test or chest x-ray suggestive of active or healed TB or positive contact history with a subject with active TB within the past 3 months. If patients have a positive Mantoux test but a negative QuantiFERON Gold test, they may be enrolled. -a serious infection during the 3 months prior study entry (hospitalised or received IV antibiotics for an infection). -chronic or recurrent infectious disease. -systemic fungal infections. -opportunistic infection within 3 months prior to screening. -subjects known, or suspected, to be infected with HIV, hepatitis B, or hepatitis C. -subjects with planned joint replacement surgery or a history of infected joint prosthesis or who have received antibiotics for a suspected infection of a joint prosthesis if that prosthesis has not been removed or replaced. 13. Subjects with a known history of demyelinating diseases such as multiple sclerosis or optic neuritis. 14. Subjects with evidence of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, psychiatric, or cerebral disease. 15. Concurrent CHF, including medically controlled, asymptomatic CHF or ECG findings suggestive of CHF. 16. Subjects receiving cytotoxic drugs including cyclophosphamide, cyclospo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of ART621 on the signs and symptoms of moderate to severe RA in patients concomitantly taking methotrexate as assessed by the proportion of subjects achieving an ACR20 response after 12 weeks treatment.;Secondary Objective: Evaluate the dose-response of ART621 against signs and symptoms of moderate to severe RA as assessed by proportion of subjects meeting ACR50 and ACR70 improvement criteria, changes in ACR hybrid score and individual ACR components, DAS28 response rate and DAS28 scores, LDAS analysis, erythrocyte sedimentation rate, C-reactive protein, individual dimensions of the Health Assessment Questionnaire and the patients assessment of fatigue. Evaluate safety, tolerability of ART621 (vital signs, ECG, clinical chemistry, haematology, urinalysis, physical examination and AE reporting). Assess impact of ART621 on quality of life as assessed by SF-36, RAQoL questionnaires. Assess immunogenicity profile of ART621 as assessed by development of human-anti-human antibodies. Investigate plasma concentration versus time profile and PK of ART621 in subjects with RA. Assess the effects of ART621 on immunological parameters and other disease biomarkers. ;Primary end point(s): The primary endpoint will be the proportion of subjects achieving an ACR20 improvement in RA symptoms at Week 12 or study termination, or on withdrawal from the study. A subject will be considered to achieve an ACR20 response if all of the following occur: • An improvement of = 20% in the swollen joint count (66 joints) • An improvement of = 20% in the tender joint count (68 joints) • An improvement of = 20% in at least 3 of the following 5 assessments: - Subject’s assessment of pain - Subject’s global assessment of disease activity - Physician’s global assessment of disease activity - Subject’s assessment of physical function, as measured by the HAQ - CRP. | — |
Countries
Czech Republic
Outcome results
None listed