E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Laquinimod is developed for the treatment of relapsing remitting multiple sclerosis.
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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 | PT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting 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 make laquinimod 0.6 mg available for all subjects who completed the placebo-controlled MS-LAQ-301 study according to the protocol and to evaluate the long-term safety, tolerability and effect on disease course of daily oral laquinimod 0.6 mg in subjects with relapsing multiple sclerosis |
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E.2.2 | Secondary objectives of the trial |
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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 |
The following ancillary studies (to be performed in a subset of subjects) and their objectives are listed below:
MRI: Subjects who participated in the Frequent MRI ancillary study during the MS-LAQ-301 study will be offered to continue to undergo MRI scans during the open-label extension study.
-MRI is one of the most acceptable ways to follow-up on subjects with Multiple Sclerosis, the frequent MRI may provide a closer follow-up on the disease status.
Magnetization Transfer (MT): Subjects who participated in the MT ancillary study during the MS-LAQ-301 study will be offered to continue to undergo MT scans during the open-label extension study.
-The MT scanning is performed following a regular MRI procedure and provides a different parameter for the assessment of axonal integrity or axonal loss.
Magnetic Resonance Spectroscopy (MRS): Subjects who participated in the MRS ancillary study during the MS-LAQ-301 study will be offered to continue to undergo MRS scans during the open-label extension study.
-The MRS scanning is performed following a regular MRI procedure and provides a different parameter for the assessment of axonal integrity or axonal loss.
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E.3 | Principal inclusion criteria |
1.Subjects must have completed the Termination visit of MS-LAQ-301 (completion of all Termination visit activities) according to the MS-LAQ-301 protocol. 2.Women of child-bearing potential must practice an acceptable method of birth control during the study and up to 30 days after the last dose of the study drug. Hormonal contraception must be accompanied by an additional barrier method of birth control (male or female condom, diaphragm with spermicide). 3.Subjects must be willing and able to comply with the protocol requirements for the duration of the study. 4.Subjects must be able to comprehend, sign and date a written informed consent prior to entering the MS-LAQ-301E study.
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E.4 | Principal exclusion criteria |
Exclusion Criteria: 1.Premature discontinuation from the MS-LAQ-301 study, for any reason. 2.Pregnancy [according to urine dipstick β-HCG test performed at Baseline (Month 0E) visit] or breastfeeding. 3.Subjects with clinically significant or unstable medical or surgical condition detected or worsened during the MS-LAQ-301 study, which preclude safe participation and completion of the MS-LAQ-301E study. Acute exacerbation of MS will not exclude participation in the MS-LAQ-301E study. 4.Use of inhibitors of CYP3A4 within 2 weeks prior to baseline visit (V0E, Month 0E).
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E.5 End points |
E.5.1 | Primary end point(s) |
There is no primary endpoint in this study. The statistical analyses of this study will be exploratory in nature. The outcome measures are as follows:
1.To assess the long-term safety and tolerability of daily oral laquinimod 0.6 mg in subjects with relapsing multiple sclerosis. Safety and Tolerability Outcome Measures: Safety: Adverse events Vital signs ECG findings Clinical laboratory parameters
Tolerability: Proportion of subjects (%) who prematurely discontinued from the study, reason of discontinuation and the time to withdrawal. Proportion of subjects (%) who prematurely discontinued from the study due to AEs and the time to withdrawal
2.To assess the long-term effect of laquinimod 0.6 mg on disease course, as assessed by several parameters: Number of confirmed relapses Progression of disability as measured by the EDSS score (including FS and AI) Progression of disability as measured by the MSFC score Binocular low-contrast visual acuity using the 100%, 2.5% and 1.25% contrast level charts [Sloan letter (Appendix 9) or Tumbling-E (Appendix 10)] Subject-reported fatigue as assessed by the Modified Fatigue Impact Scale (MFIS)
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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 | No |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.6.13.1 | Other scope of the trial description |
long-term effect on disease course |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 85 |
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 | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |