| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 compare the efficacy and the safety of 3 dose levels of oral TMI-005 in comparison with placebo in subjects with active RA who have been receiving stable doses of MTX. |
|
| E.2.2 | Secondary objectives of the trial |
1. To compare the efficacy and the safety of TMI-005 among 3 dose levels.
2. To assess health outcome measures.
3. To assess ACR 20, ACR 50, and ACR 70 responses at all time points and
components of ACR response criteria.
4. To assess disease activity score-28 (DAS-28).
5. To assess other measures of disease activity.
6. To assess population pharmacokinetics (PK) of TMI-005.
7. To search for biomarkers that may correlate with severity of RA and/or clinical
response to TMI-005 using peripheral blood mononuclear cells (PBMC) gene
expression and, possibly, protein expression profiling in a subset of subjects at
selected sites. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Meet American College of Rheumatology (ACR) criteria for RA.
2. Have active RA consisting of ≥ 5 swollen and ≥ 5 painful joints (28-joint count) and at least 1 of the following 3: erythrocyte sedimentation rate (ESR) (Westergren) ≥ 28 mm/hour; C-reactive protein (CRP) ≥ 15 mg /L; or morning stiffness ≥ 45 minutes at both screening and baseline (CRP value obtained from screening visit may be used to meet this criteria).
3. Disease duration of at least 6 months.
4. Disease onset at > 16 years of age.
5. Age 18 to 75 years.
6. Must be currently treated with a stable, well-tolerated dose of MTX (7.5 to 20 mg) given once weekly for at least 12 weeks before the baseline visit.
7. Women of childbearing potential, who have a negative pregnancy test result, as well as all male subjects, must agree to use a medically acceptable method of birth control during the study and for at least 12 weeks after the last dose of test article.
8. Be able and willing to comply with study visits and procedures specified in this protocol.
9. Understand, sign, and date the written voluntary informed consent form at the screening visit before any protocol-specific procedures are performed. |
|
| E.4 | Principal exclusion criteria |
Screening Visit
1. Any prior use of anti-TNF alpha biologics, rituximab, receipt of anti-CD4 or diphtheria interleukin-2 fusion protein or other immunosuppressive biologics (except for anakinra).
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. Pregnant or breastfeeding women or women planning to become pregnant during the study or within 12 weeks after the last dose of test article.
4. History of poor compliance or history of drug abuse/alcohol abuse, excessive alcohol beverage consumption or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent.
5. Any condition that the physician judges could be detrimental to subjects participating in this study, including any clinically important deviations from normal clinical laboratory values or important concurrent medical events.
Baseline Visit
1. Within 12 weeks before baseline, a change in dose of MTX.
2. Within 4 weeks before baseline, current use of more than 1 nonsteroidal anti-inflammatory drug (NSAID) or change of dose of the NSAID or NSAID use greater than the maximum recommended dose.
3. Within 4 weeks before baseline, use of more than 10 mg/day of prednisone or equivalent or change in the dose of prednisone or equivalent.
4. Within 4 weeks before baseline, receipt of an intra-articular corticosteroid injection or bolus intramuscular or intravenous treatment with corticosteroids (> 20 mg prednisone or equivalent).
5. Within 4 weeks before baseline, receipt of the following DMARDs:
hydroxychloroquine, chloroquine, sulfasalazine, auranofin, and intramuscular gold, cyclosporine, azathioprine, leflunomide, D-penicillamine and anakinra.
6. Within 4 weeks before baseline, receipt of any investigational drug or investigational biological agent. Within 12 weeks before baseline, receipt of an investigational agent that is unknown.
7. Within 8 weeks before baseline, receipt of any live (attenuated) vaccines.
8. Within 24 weeks before baseline, receipt of cyclophosphamide. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy
The primary efficacy variable is the ACR 20 response rate at Week 12.
Safety
Spontaneously reported signs and symptoms.
Scheduled physical examinations (evaluation of shoulder abduction, body weight measurements).
Elicited history reported by subjects.
Vital sign measurements.
12-lead electrocardiogram (ECG).
Posteroanterior (PA) and lateral chest radiographs.
Clinical laboratory evaluations.
More frequent safety evaluations may be performed if clinically indicated, or at the discretion of the investigator.
Monitor all adverse events (AEs). |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | Yes |
| 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 |
|
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
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