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 | 10028245 |
E.1.2 | Term | Multiple sclerosis |
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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 |
To assess the efficacy, of 0.6 mg daily dose of laquinimod as compared to placebo in RRMS subjects, as measured by the number of confirmed relapses during the study period. |
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E.2.2 | Secondary objectives of the trial |
 Accumulation of physical disability measured by the time to confirmed progression of EDSS during the study period (A confirmed progression of EDSS is defined as a 1 point increase from baseline on EDSS score if baseline EDSS was between 0 and 5.0, or a 0.5 point increase if baseline EDSS was 5.5, confirmed 3 months later. Progression can not be confirmed during a relapse).  The cumulative number of enhancing lesions on T1-weighted images taken on months 12 and 24 (and 30 in case of extending the study for 6 months).  The cumulative number of new hypointense lesions on enhanced T1 scans at months 12and 24 (and 30 in case of extending the study for 6 months).  The cumulative number of new T2 lesions on scans taken on months 12 and 24(and 30 in case of extending the study for 6 months). |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOGENETICA
FARMACOCINETICA/FARMACODINAMICA
ALTRI SOTTOSTUDI: Risonanza magnetica frequente Risonanza magnetica MT Risonanza magetica MRS Risposta immunologica Potenziale meccanismo d'azione del farmaco
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E.3 | Principal inclusion criteria |
1. Subjects must have a confirmed and documented MS diagnosis as defined by the Revised McDonald criteria [Ann Neurol 2005: 58:840-846], with a relapsing-remitting disease course. 2. Subjects must be ambulatory with converted Kurtzke EDSS score of 0-5.5. 3. Subjects must be in a stable neurological condition and free of corticosteroid treatment [intravenous (iv), intramuscular (im) and/or per os (po)] 30 days prior to screening (month -1). 4. Subjects must have had experienced one of the following:  At least one documented relapse in the 12 months prior to screening  At least two documented relapses in the 24 months prior to screening  One documented relapse between 12 and 24 months prior to screening with at least one documented T1-Gd enhancing lesion in an MRI performed within 12 months prior to screening. 5. Subjects must be between 18 and 55 years of age, inclusive. 6. Subjects must have disease duration of at least 6 months (from the first symptom) prior to screening. 7. Women of child-bearing potential must practice an acceptable method of birth control [acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partners vasectomy or double-barrier method (condom or diaphragm with spermicide). 8. Subjects must be able to sign and date a written informed consent prior to entering the study |
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E.4 | Principal exclusion criteria |
1. Subjects with progressive forms of MS 2. An onset of relapse, unstable neurological condition or any treatment with corticosteroids [intravenous (iv), intramuscular (im) and/or per os (po)] or ACTH between month -1 (screening) and 0 (baseline). 3. Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening. 4. Use of immunosuppressive including Mitoxantrone (Novantrone) or cytotoxic agents within 6 months prior to the screening visit. 5. Previous use of either of the following: natalizumab (Tysabri), cladribine, laquinimod. 6. Previous treatment with glatiramer acetate (Copaxone) Interferon-β (either 1a or 1b) or IVIG within 2 months prior to screening visit. 7. Systemic corticosteroid treatment of ≥30 consecutive days duration within 2 months prior to screening visit. 8. Previous total body irradiation or total lymphoid irradiation. 9. Previous stem cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation. 10. A known history of tuberculosis. 11. Acute infection two weeks prior to baseline visit. 12. Major trauma or surgery two weeks prior to baseline 13. A history of vascular thrombosis (excluding catheter-site superficial venous thrombophlebitis). 14. A carrier state of factor V Leiden mutation (either homo- or heterozygous) as disclosed at screening. 15. Positive screening test for Hepatitis B surface antigen, Hepatitis C antibody, or HIV antibody as disclosed at screening visit. 16. Use of potent inhibitors of CYP3A4 within 2 weeks prior to baseline visit (1 month for fluoxetine) see detailed list in Appendix 5 17. Use of amiodarone within 2 years prior to screening visit. 18. Pregnancy or breastfeeding. 19. Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation, as determined by medical history, physical examinations, ECG, laboratory tests or chest X-ray. Such conditions may include:  A cardiovascular or pulmonary disorder that cannot be well-controlled by standard treatment permitted by the study protocol.  A gastrointestinal disorder that may affect the absorption of study medication.  Renal or metabolic diseases.  Any form of chronic liver disease, including known non-alcoholic steatohepatitis.  A ≥2xULN serum elevation of either of the following at screening: ALT, AST or direct bilirubin  A QTC interval (obtained from either 2 ECG recordings at screening or from the mean value calculated from 3 measurements at baseline visit) which is >450msec.  A family history of Long- QT syndrome.  A history of drug and/or alcohol abuse.  Major psychiatric disorder. 20. A known history of sensitivity to Gd. 21. Inability to successfully undergo MRI scanning. 22. Known drug hypersensitivity that would preclude administration of laquinimod, such as hypersensitivity to: mannitol, meglumine or sodium stearyl fumarate. |
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E.5 End points |
E.5.1 | Primary end point(s) |
 The number of confirmed relapses during the double blind study period |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
e' prevista una fase di estensione in aperto |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
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 | 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 | 4 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |