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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E.1.1.1 | Medical condition in easily understood language |
Relapsing-remitting multiple sclerosis is a chronic inflammatory disease that affects the central nervous system. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
ancillary studies described within the core protocol will be performed in a subset of subjects: 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. During the MS-LAQ-301E study, these scans will be performed at Months 0E [Baseline (This is the Termination scan of the MS-LAQ-301 study)] and then every 12 months thereafter, until Termination/Early discontinuation. 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. During the MS-LAQ-301E study, these scans will be performed at Months 0E [Baseline (Termination visit of the MS-LAQ-301 study)] (this scan is a part of the MT ancillary study under the MS-LAQ-301 protocol) and then every 12 months thereafter until Termination/Early discontinuation. 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. During the MS-LAQ-301E study, these scans will be performed at Months 0E [Baseline (Termination visit of the MS-LAQ-301 study)] (this scan is a part of the MRS ancillary study under the MS-LAQ-301 protocol) and then every 24 months thereafter, until Termination/Early discontinuation. |
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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 (for example women who are not postmenopausal or surgically sterilized) must practice two acceptable methods of birth control for the duration of the study and until 30 days after the last dose of study medication [acceptable methods of birth control in this open label extension phase include: intrauterine devices, barrier methods (condom or diaphragm with spermicide), and hormonal methods of birth control (e.g. oral contraceptive, contraceptive patch, and long-acting injectable contraceptive)]. 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.5.1.1 | Timepoint(s) of evaluation of this end point |
Number of confirmed relapses: -On-Study Relapse Evaluation throughout the treatment duration Subjects will be instructed to telephone their study site within 48 hours should any symptoms suggestive of a relapse appear. The Treating Neurologist/ Physician will evaluate the subject once any symptom suggestive of a relapse occurs. All other parameters: -At Months 0 Baseline [(Termination visit of the MS-LAQ-301 study)], and month 6 and every 6 months thereafter. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 78 |
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 |
Georgia |
Israel |
Russian Federation |
Serbia |
Ukraine |
United States |
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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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In this open-label study, the subjects will be treated with Laquinimod 0.6 mg as long as the Sponsor continues the development of laquinimod 0.6 mg for RRMS. |
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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 | 9 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |