E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary progressive multiple sclerosis |
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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 compare the clinical efficacy of 500 mg MBP8298 given intravenously every six months for a period of two years, to placebo, in subjects diagnosed with SPMS who are positive for the HLA DR2 and/or DR4 haplotype. Clinical efficacy is defined as a statistically and clinically significant increase in the time to confirmed worsening of disability as measured by EDSS.
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E.2.2 | Secondary objectives of the trial |
•To assess safety of MBP8298 synthetic peptide in all subjects irrespective of genotype. •To compare the clinical efficacy of 500 mg MBP8298 given intravenously every six months for a period of two years, to placebo, in subjects diagnosed with SPMS who are negative for the HLA DR2 and/or DR4 haplotype. •To assess the effects of MBP8298 on MRI parameters. •To confirm that treatment with MBP8298 induces immunological tolerance or shift in functional response profile to MBP peptide (82-98) and determine whether this is dependent on HLA subtype •To determine whether MBP8298 induces immunological tolerance or shift in functional response profile to other MBP epitopes and other myelin antigens (e.g. PLP, MOG) indicating the stop of epitope spreading and whether this too is dependent on HLA subtype. •To confirm the ratio of HLA DR2/4 positive to HLA DR2/4 negative subjects in the SPMS population. •To determine whether MBP8298 improves the quality of life of SPMS patients.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male or female subjects, 18-65 years of age,
2. Documented history of SPMS. SPMS is defined as an MS patient who has been diagnosed with MS for at least 3 years, and in the 3 year period prior to enrolment must have documented progression of their pyramidal or cerebellar Kurtzke functional subscores (FSS). (In the absence of documented FSS changes, clinical notes documenting changes consistent with these changes will be acceptable). The subject must also have experienced at least 1 acute relapse as part of their diagnosis of RRMS. Only one relapse prior to diagnosis of MS can be in accordance with the McDonald diagnostic criteria as long as cranial MRI findings consistent with the diagnosis of MS are also present. 3. Absence of relapse in the 3 months prior to baseline.
4. EDSS of 3 . 5 – 6 . 5.
5. Pyramidal or Cerebellar FSS ≥ 3
6. A cohort of 100 HLA DR2/4 negative patients is required. Once enrollment to this cohort is complete, all further patients are required to be HLA DR2/4 positive.
7. Subject must be able and willing to give meaningful, written informed consent prior to participation in the trial, in accordance with regulatory requirements,
8. In the Investigator’s opinion, subjects must be reliable, compliant, and agree to cooperate with all trial evaluations.
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E.4 | Principal exclusion criteria |
1. Diagnosis of Primary Progressive MS.
2. Subjects have previously received MBP8298.
3. A recent history of malignancy, with the exclusion of basal cell carcinoma. All patients with a history of malignancy must be discussed, approved, and a waiver issued by the Sponsor’ Medical Monitor prior to randomization
4. Steroid therapy within 30 days prior to first study specific procedure, or any other treatment known to be used for putative or experimental MS treatment.
5. Therapy with ß-interferon, glatiramer acetate within 3 months or mitoxantrone, cyclophosphamide, methotrexate, azathioprine, or any other immuno-modulating (e.g. IVIG) or immunosuppressive drugs including recombinant or non-recombinant cytokines or plasma exchange within 6 months prior to performance of the first study-specific test, with the exception of corticosteroids or ACTH for relapse treatment.
6. Initiation or discontinuation of therapy with 4-AP or 3,4-DAP at any time during the study period.
7. History of anaphylactic/anaphylactoid reactions to glatiramer acetate.
8. Abnormal laboratory values at the Baseline Visit deemed by the Investigator to be clinically significant.
9. Known allergy to Gadolinium-DTPA.
10. Treatment at any time with Cladribine, total lymphoid irradiation, monoclonal antibody treatment e.g. anti-CD4, anti-CD52, anti-VLA4, Anti-CD20.
11. Treatment at any time with an altered peptide ligand.
12. Any conditions that could interfere with the performance of study specific procedures e.g. MRI.
13. Previous randomization to this study.
14. Known positivity for HIV, Hepatitis B, or Hepatitis C.
15. Participation in any other non-MS clinical trial within 30 days prior to performance of the first study specific test (the screening/baseline visit), or any investigational therapy in the past 6 months.
16. Females who are breast feeding, pregnant (pregnancy test at Screening), or not using a medically approved method of contraception regularly.
17. Known or suspected current or past alcohol or drug abuse (within the last year).
18. Any medical, psychiatric or other condition that could result in a subject not being able to give fully informed consent, or to comply with the protocol requirements.
19. Any other condition that, in the Investigator’s opinion, makes the subject unsuitable for participation in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is a statistically and clinically significant increase in the time to confirmed worsening of disability as measured by EDSS. |
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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 | Yes |
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 | Information not present in EudraCT |
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 |
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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) | 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 | No |
E.8.1.7.1 | Other trial design description |
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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.8.5 | 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 | Information not present in EudraCT |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |