E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-remitting Multiple Sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
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 assess the safety of extended treatment with DAC HYP monotherapy in subjects with RRMS. |
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E.2.2 | Secondary objectives of the trial |
To assess the long-term immunogenicity of DAC HYP and to assess the durability of response to DAC HYP in preventing MS relapse, slowing disability progression, and reducing new MS lesion formation in this study population. |
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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 |
2013-2014 Influenza Vaccine Substudy
The objective of the optional administration of the of the 2013-2014 trivalent seasonal influenza vaccine is to assess the effect of DAC HYP treatment on the immune response to licensed trivalent seasonal influenza vaccine, as defined by HI titer. |
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E.3 | Principal inclusion criteria |
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use PHI in accordance with national and local subject privacy regulations. 2. Must be a subject from Study 205MS202 who completed at least 52 weeks and must have been compliant with the 205MS202 protocol in the opinion of the Investigator. 3. Women of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 4 months after their last dose of study treatment.
Inclusion criteria for the 2013-2014 Influenza Vaccine Substudy: 1. Subjects must provide specific informed consent for the 2013-2014 Influenza Vaccine Substudy 2. Subjects must have completed at least 3 months of uninterrupted therapy with DAC HYP prior to entering the 2013-2014 Influenza Vaccine Substudy |
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E.4 | Principal exclusion criteria |
1. Subjects with any significant change in their medical status from the previous study that would preclude administration of DAC HYP, including laboratory tests or a current clinically-significant condition that, in the opinion of the Investigator, would have excluded the subject’s participation in the 205MS201 or 205MS202 studies. The Investigator must re review the subject’s medical fitness for participation and must consider any diseases that would preclude treatment. 2. Any subject who has permanently discontinued study treatment in Study 205MS202 due to an AE. 3. Current enrollment in any investigational drug study other than 205MS202. 4. Ongoing treatment with any approved or experimental disease-modifying treatment for MS. 5.For subjects currently taking valproic acid, carbamazepine, lamotrigine, or phenytoin: Subjects treated with any of these agents for fewer than 6 months prior to study entry are excluded from study participation unless they discontinue the agent(s) prior to study entry.* - Subjects treated with 2 or more of these agents for more than 6 months prior to study entry are excluded from study participation unless they reduce to ≤1 agent prior to study entry.* - Subjects who have had dose escalations of one of these agents within the 6 months prior to study entry are excluded from study participation unless they revert to a previous dose that had been used for at least 6 months prior to study entry or unless they discontinue the agent prior to study entry.* *Subjects may use an alternative medication allowed by the protocol as needed. Note: Subjects who have been taking 1 of these medications at a stable dose for at least 6 consecutive months prior to study entry may continue to receive the medication without alteration and are eligible for study participation. 6. Subjects who are currently receiving treatment with isoniazid, propylthiouracil, or nimesulide at the time of study entry and are not able to discontinue the agent or change to an alternative medication allowed by the protocol prior to initiation of study treatment in this study. 7. Unwillingness or inability to comply with the requirements of the protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject’s ability to comply with the protocol.
Exclusion Criteria for the 2013-2014 Influenza Vaccine Substudy: 1. Subject has had a severe allergic reaction (e.g., anaphylaxis) to eggs, egg proteins (a vaccine component), or any other component of the trivalent seasonal influenza vaccine. 2. Subject has had a serious reaction to previous influenza vaccination. 3. Subject has a known latex allergy. 4. Subject was previously vaccinated for the 2013-2014 influenza season strain. 5. Subject had a respiratory illness in the 2 weeks preceding the planned vaccination with the 2013-2014 trivalent seasonal influenza vaccine. 6. Subject has any ongoing adverse event or laboratory abnormality in SELECTED that has resulted in suspension of DAC HYP treatment at the time of enrollment into the 2013-2014 Influenza Vaccine Substudy. 7. Subject has received in the last 3 months: blood products oral or intravenous corticosteroids intravenous immunoglobulins 8. Subject has received any vaccination in the last 4 weeks. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints of the study are AEs, including SAEs, discontinuation of DAC HYP due to AEs, and withdrawals due to AEs. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Clinical Adverse Events: All treatment-emergent events during 205MS203 will be included in the evaluation of safety. Treatment emergent includes any event that either occurs or worsens in severity after the onset of study treatment in 205MS203. Clinical Adverse Events over Time: In order to assess whether the incidence of events changes over time, the incidence will also be summarized by time period. |
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E.5.2 | Secondary end point(s) |
• Immunogenicity • Sustained disability progression defined by at least a 1.0-point increase on the EDSS from a baseline EDSS ≥1.0 that is sustained for 12 weeks, or at least a 1.5-point increase on the EDSS from a baseline EDSS <1.0 that is sustained for 12 weeks • Annual change in total number and volume of new or newly enlarging T2 hyperintense lesions, Gd-enhancing lesions, T1 hypointense lesions, and brain atrophy on brain MRI • Annualized Relapse Rate (ARR) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Immunogenicity -at baseline, every 12 weeks through week 48, at week 96, at week 144, at week 192, at week 240, at week 288, at final study visit, at relapse assessment if applicable, and at early termination visit if applicable. EDSS- at baseline, every 24 weeks, and at early termination visit if applicable MRI - at baseline, week 48, 96, 192, 240, and 288. ARR- annually
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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 | Yes |
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 |
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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) | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
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 | No |
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 |
India |
Russian Federation |
Ukraine |
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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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As stated in the Protocol |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |