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 document the long-term safety and tolerability of teriflunomide when added to treatment with interferon-beta or glatiramer acetate in patients with multiple sclerosis with relapses |
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E.2.2 | Secondary objectives of the trial |
To document the long-term effect on relapse rate, disability rate and MRI variables |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Multiple Sclerosis patients who have completed the last study visit (visit 14) at week 24 of either study PDY6045 or PDY6046, and who are still meeting eligibility criteria for receiving treatment in the previous study and with a signed informed consent to extend their participation.
An informed consent must be obtained in writing from the subject for this extension study prior enrollment. Subjects must be willing to continue their current interferon or glatiramer acetate therapy and continue their double-blind treatment. For those subjects who have not had HIV testing the in core studies (PDY6045 or PDY6046) an informed consent for HIV testing must be signed for LTS6047. |
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E.4 | Principal exclusion criteria |
1. Significantly impaired bone marrow function or significant anemia, leukopenia, or thrombocytopenia • Hematocrit <24% and/or • Absolute white blood cell count <4,000 cells/mm3 (µL) and/or • Platelet count <150,000 cells/mm3 (µL) and/or • Absolute neutrophil ≤ 1,500 cells/mm3 (µL) 2. Congenital or acquired severe immunodeficiency, a history of cancer (except for basal or squamous cell skin lesions which have been surgically excised, with no evidence of metastasis), lymphoproliferative disease, or any subject who has received lymphoid irradiation 3. Known history of active tuberculosis not adequately treated 4. Persistent significant or severe infection or HIV positive 5. Pregnancy 6. Breastfeeding 7. Wishing to parent children during the course of the trial 8. Therapies, which are disallowed: phenytoin, warfarin, tolbutamine, or cholestyramine 9. Prior or concomitant use of cladribine, mitoxantrone, or the immunosuppressant agents azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate 10. Liver function impairment or persisting elevations of serum glutamic pyruvic transaminase (SGPT)/ alanine transaminase (ALT), or serum glutamic oxaloacetic transaminase (SGOT)/ aspartate transaminase (AST), or direct bilirubin >1.5-fold the upper limit of normal (ULN) 11. Persisting elevations of serum amylase or lipase greater than 2-fold the upper limit of normal 12. Known history of chronic active hepatitis 13. Known history of chronic pancreatic disease or pancreatitis 14. Hypoproteinemia (e.g., in case of severe liver disease or nephrotic syndrome) with serum albumin <3.0 g/dL 15. Moderate to severe impairment of renal function, as shown by serum creatinine >133 µmol/L (or >1.5 mg/dL) 16. Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol 17. Clinically relevant cardiovascular, hypertensive (defined as blood pressure [BP] ≥160/100 mm/Hg), hepatic, neurological, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult or that would put the subject at risk by participating in the study 18. Severe depressive disorder and/or suicidality 19. Unlikely to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study 20. Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety ( Adverse event reports,laboratory parameters,ECG,CT of MRI image of pancreas and vitals signs) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 | Yes |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
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 | 5 |