E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the long-term safety of oral TMI-005 in subjects with RA who have been receiving MTX. |
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E.2.2 | Secondary objectives of the trial |
1. To compare the efficacy of TMI-005 among various dose ranges. 2. To assess health outcome measures. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Screening visit if week 12 visit of study 200 is > 4 weeks from the first visit of this study (201). 1. Have completed 12 weeks of treatment for Protocol 3140A1-200-WW. 2. Negative serum b-human chorionic gonadotropin (b-HCG) pregnancy test at screening for all women of childbearing potential. A woman of childbearing potential is one who is biologically capable of becoming pregnant. This includes women who are using contraceptives, have had a tubal ligation or whose sexual partners are either sterile or using contraceptives. 3. Sexually active women of childbearing potential must agree and commit to use of a medically acceptable form of contraception and for at least 12 weeks after the last dose of test article. Medically acceptable forms of contraception include sexual abstinence, oral contraceptives, injectable or implantable methods, intrauterine devices, or properly used barrier contraception. 4. Sexually active men must agree and commit to use a medically accepted form of contraception during the study and for at least 12 weeks after the last dose of test article. 5. Stable dose of methotrexate (7.5 to 20 mg) 4 weeks prior to baseline visit. 6. Stable dose of 1 NSAID for at least 2 weeks prior to baseline visit. 7. Stable dose of prednisone, or its equivalent (not more than 10 mg/day) for at least 2 weeks prior to the baseline visit. 8. No inta-articular corticosteroid injection or bolus intramuscular or intravenous treatment with corticosteroid (>20 mg prednisone or equivalent). |
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E.4 | Principal exclusion criteria |
1. Subjects who did not complete 12 weeks of test article treatment in the Protocol 3140A1-200-WW trial. 2. Largely or wholly incapacitated with the subject bedridden or confined to a wheelchair, permitting limited or no self-care (ACR Functional Class IV, 1987). 3. Any clinically relevant protocol violation observed during the course of the Protocol 3140A1-200-WW. 4. Abnormal haematology or chemistry profiles: white blood cell count ≤ 3.5 x 109 /L; haemoglobin ≤ 85 g/L or 5.3 mmol/L; haematocrit ≤ 27%; platelet count ≤ 125 x 109 /L or ≥ 1000 x10 9/L; serum creatinine ≥ 175 mmol/L (≥ 2.0mg/dL); total bilirubin > 1.5 times the ULN, aspartate aminotransferase AST/SGOT) and alanine aminotransferase (ALT) ≥ 1.2 times the laboratory’s upper limit of normal at Baseline. 5. Any use of anti-TNF alpha biologics, rituximab, receipt of any anti-CD4 or diphtheria interleukin-2 fusion protein or other immunosuppressive biologics (except for anakinra). 6. Within 4 weeks before baseline, receipt of the following DMARDs: hydroxychloroquine, chloroquine, sulfasalazine, auronofin, and intramuscular gold, cyclosporine, azathioprine, leflunomide,D-penicillamine and anakinra. 7. Within 4 weeks before baseline receipt of any investigational drug (except for test article received in study 3140A1-200-WW) or investigational biological agent. Within 12 weeks before the baseline visit, receipt of an investigational agent that is unknown. 8. Within 8 weeks before baseline, receipt of any live (attenuated) vaccines. 9. Within 24 weeks before baseline, receipt of cyclosphosphamide. 10. Clinically relevant concurrent medical events including: - uncompensated congestive heart failure. - diagnosis of multiple sclerosis or other central demyelinating diseases. - presence or history of confirmed blood dyscrasias. - cancer or history of cancer (other than resected cutaneous basal cell or squamous cell carcinoma). - serious infection (infection association with hospitalization and/or intravenous antibiotics) within 4 weeks of test article administration or active infection at Baseline visit. - any condition that, in the physician’s judgment, might cause this study to be detrimental to the subject. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The following clinical assessment of subject’s response to therapy will be performed at the scheduled study visits: · Complete standardized joint assessment (performed by the same investigator throughout the study): number of painful or tender joints and number of swollen joints (28 joints evaluated). · Duration of morning stiffness in minutes. · CRP/ESR. · Physician global assessments of disease activity · Patient global assessments of disease activity · Pain VAS. Health Outcome measurements: HAQ, patient general health VAS, and Fatigue VAS. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Subjects will continue to participate in this trial until the results of the 3140A1-200-WW interim analysis have been analyzed and an appropriate dose chosen. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |