E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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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 |
The primary objectives of this study are to: 1. Determine the efficacy of oral CF101 when administered daily for 12 weeks when added to weekly methotrexate in patients with active rheumatoid arthritis (RA) despite ≥6 months treatment with methotrexate; 2. Determine the safety of chronically-administered daily oral CF101 when administered in combination with weekly methotrexate in patients with active RA; and 3. Select the most appropriate dose of CF101 to advance into definitive efficacy trials in RA patients.
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this trial is an exploratory evaluation of the relationship between biomarkers (peripheral blood mononuclear cell adenosine 3 receptor (A3R) mRNA expression and serum cytokine profiles) and clinical response to CF101 in patients with RA. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria: 1. Males and females ages 18-75 years 2. Meet the criteria of the American College of Rheumatology for RA (Arnett FC et al. Arthritis Rheum 1988;31:315-324, Appendix 1) 3. Not bed- or wheelchair-bound 4. Active RA, as indicated by the presence of (a) ≥6 swollen joints (28 joint count); AND (b) ≥6 tender joints (28 joint count); AND either: (c) Westergren ESR of ≥28 mm/hour; OR (d) CRP level above the upper limit of normal for the central reference laboratory 5. Treatment with weekly oral or parenteral methotrexate for ≥6 months prior to baseline 6. Methotrexate route of administration has been unchanged for ≥2 months prior to baseline 7. Dose of methotrexate has been stable at 15-25 mg/week for ≥2 months, and is expected to remain stable throughout the study; the stable dose of methotrexate may alternatively be 10-12.5 mg/week if documented toxicity has precluded a higher dose 8. If taking hydroxychloroquine or chloroquine, administration duration has been ≥3 months and dose has been stable for ≥2 months prior to baseline 9. If taking a nonsteroidal anti-inflammatory agent (NSAID), dose has been stable for at least 1 month prior to baseline, and will remain unchanged during protocol participation 10. If taking an oral corticosteroid, dose is ≤10 mg/day prednisone or equivalent, has been stable for at least 1 month prior to the stabilization period, and will remain stable through the stabilization and entire treatment and follow-up period 11. Absence of clinically significant findings, such as interstitial pneumonitis or active pulmonary infection, on chest X-ray taken within 6 months prior to screening 12. In the Investigator’s opinion, the ability to understand the nature of the study and any hazards of participation, and to communicate satisfactorily with the Investigator and to participate in, and to comply with, the requirements of the entire protocol 13. Negative screening serum pregnancy test for female patients of childbearing potential 14. Females of childbearing potential must utilize, throughout the course of the trial, 2 methods of contraception deemed adequate by the Investigator (for example, oral contraceptive pills plus a barrier method) 15. All aspects of the protocol explained and written informed consent obtained |
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E.4 | Principal exclusion criteria |
Exclusion Criteria: 1. Receipt of any of the following for at least a 1 month stabilization period prior to dosing: sulfasalazine, oral or injectable gold, azathioprine, minocycline, penicillamine, anakinra 2. Receipt of etanercept for at least a 6 week period prior to dosing 3. Receipt of cyclosporine, infliximab or adalimumab for at least a 2 month period prior to dosing 4. Receipt of leflunomide for at least a 2 month period prior to screening, unless patient has undergone cholestyramine washout at least 1 month prior to dosing 5. Receipt of cyclophosphamide for at least a 6 month period prior to dosing 6. Receipt of rituximab at any previous time 7. Participation in a previous trial CF101 trial 8. Use of oral corticosteroids >10 mg of prednisone, or equivalent, per day 9. Change in NSAID dose level for 1 month prior to dosing 10. Change in oral corticosteroid dose level during the 1 month prior to, or during, the stabilization period 11. Change in hydroxychloroquine or chloroquine dose level during the 2 months prior to, or during, the stabilization period 12. Receipt of parenteral or intra-articular corticosteroids during the 1 month prior to, or during, the stabilization period 13. Presence or history of uncontrolled asthma 14. Presence or history of uncontrolled arterial hypertension or symptomatic hypotension 15. Significant cardiac arrhythmia or conduction block, congestive heart failure, or any other evidence of clinically significant heart disease; other clinically significant findings on screening electrocardiogram (ECG) 16. Hemoglobin level <9.0 gm/dL at the screening visit 17. Platelet count <125,000/mm3 at the screening visit 18. White blood cell count <3000/mm3 at the screening visit 19. Serum creatinine level outside the central laboratory’s normal limits at the screening visit 20. Liver aminotransferase (ALT and/or AST) levels greater than 1.25 times the central laboratory’s upper limit of normal at the screening visit 21. Known or suspected immunodeficiency or human immunodeficiency virus positivity 22. Pregnancy, lactation, or inadequate contraception as judged by the Investigator 23. Participation in another investigational drug or vaccine trial concurrently or within 30 days prior to screening 24. History of drug or alcohol dependence 25. History of serious drug or iodine allergy or sensitivity 26. History of malignancy within the past 5 years (excluding excised basal or squamous cell carcinoma of the skin) 27. Diagnosis of Parkinson’s Disease 28. Significant acute or chronic medical or psychiatric illness that, in the judgment of the Investigator, could compromise patient safety, limit thepatient’s ability to complete the study, and/or compromise the objectives of the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy parameteris the ACR 20 response rate (binary composite endpoint). The patient must show at least: 20% improvement in tender joint count and 20% improvement in swollen joint count AND 20% improvement in 3 of following 5: a) patient pain assessment b) patient global assessment c) Physician global assessment d) Patient self-assessed disability e)Acute-phase reactant (ESR or CRP). The primary efficacy assessment of treatment group differences will be based on the proportion of patients in each treatment group who have achieved an ACR 20 response at endpoint, defined as Week 12. Patients who discontinue prior to reaching the 12-week endpoint will be considered nonresponders. |
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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 | No |
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 | Yes |
E.6.10 | Pharmacogenetic | No |
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 | 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.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |