E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Progression of patients with Multiple System Atrophy (MSA) |
fortgeschrittene Erkrankung bei Patienten mit Multi-System-Atrophie (MSA) |
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E.1.1.1 | Medical condition in easily understood language |
patients with progressive neurodegenerative disorder |
Patienten mit fortgeschrittener neurodegenerative Erkrankung |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of EGCG vs. Placebo to reduce the progression in the motor examination (ME) of the Unified MSA Rating Scale (UMSARS-ME) from V1 to V7, (80% power, 5% P-level, 50% effect size, i.e. an expected mean yearly UMSARS-ME increase of 3.9 under verum treatment compared to 7.8 ± 6.8 (mean ± standard deviation) under Placebo-treatment.
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E.2.2 | Secondary objectives of the trial |
Clinical safety and tolerability of EGCG (physical and neurological examination, laboratory parameters, adverse events, vital signs, drop-out rates, survival rates and survival time).
To assess the efficacy of EGCG vs. Placebo to reduce the progression from V1 to V7 the following parameters are of interest:
- UMSARS total score
- clinical global impression (CGI)
- global and regional cerebral atrophy (3D MPRAGE MRI volumetry).
- global and regional cerebral iron deposition in pons and striatum (T2* MRI).
To assess any effect of ECGC vs. Placebo on the evolution of the above men-tioned parameters during the wash-out phase (from V6 to V7) to explore pos-sible symptomatic effects
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Clinical signs of MSA. Diagnosis will be made for patients with „clinical possible“ or „clinical prob-able“ Multiple System Atrophy (MSA) according to the diagnostic criteria of Gilman et al. (Neurology 2008).
2. Stadium Hoehn & Yahr I – III
3. A stable regimen for at least 1 month prior to V1 and willingness / no foreseeable need to change the regimen throughout the the 52 week follow-up period for
a. drugs acting against Parkinsonism (e.g. Levodopa, Dopamine-Agonists, Amantadine and MAO-B-Inhibitors)
b. other CNS-active substances including antidepressants and antidementive drugs.
c. drugs acting against autonomic dysfunction (e.g. ephedrin, midodrin, fludrucortison, octreo-tide, desmopresin, oxybutinine).
4.Capability and willingness to give written signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study
5. No regular consumption of green tea or EGCG
6. Not more than maximum of two cups black tea /day
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E.4 | Principal exclusion criteria |
1. Clinical signs of MSA exceeding Stadium Hoehn and Yahr III (loss of postural reflexes, no independent walking possible, inability to stand unassisted, wheelchair-bound)
2. Neurodegenerative diseases other than MSA
3. Severe liver disease with elevation of transaminases above 5folds of the upper normal level or the in-take of hepatotoxic drugs
4. Known hypersensitivity to EGCG or substances with a similar chemical structure
5. Participation in another clinical trial involving administration of an investigational medicinal product within 30 days prior to V0.
6. Known or persistent abuse of medication, drugs or alcohol
7. Subjects with a physical or psychiatric condition that may put the subject at risk, confound trial results or may interfere with the subject’s participation in this clinical trial
8. Consumption of more than 500ml grapefruit juice/day (leading to inhibition of cytochrome P-450 isoen-zyme 3A4, which may be involved in degradation of EGCG)
9. Intake of COMT-Inhibitors (e.g. Entacapone, Tolcapone)
12. Current or planned therapy with bortezomib and/ or history of plasmocytoma
13. Anemia at Screening Visit (Hb < 10g/dl)
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E.5 End points |
E.5.1 | Primary end point(s) |
The change from V1 to V7 in UMSARS-ME comparing placebo vs. verum-treated patients |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints:
• Changes from V1 to V7 in the total UMSARS score comparing placebo vs. verum treated patients
• Changes from V1 to V7 in CGI comparing placebo vs. verum treated patients
• Changes from V1 to V7 in MRI parameters (global and regional atrophy / iron deposition) comparing placebo- vs. verum treated patients
• Changes in UMSARS-ME, total UMSARS, GCI score, and MRI parameters (global and regional at-rophy / iron-deposition) from V6 to V7 comparing placebo- vs. verum-treated patients, to identify possible symptomatic effects.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Changes from V1 to V7 in the total UMSARS score comparing placebo vs. verum treated patients
• Changes from V1 to V7 in CGI comparing placebo vs. verum treated patients
• Changes from V1 to V7 in MRI parameters (global and regional atrophy / iron deposition) comparing placebo- vs. verum treated patients
• Changes in UMSARS-ME, total UMSARS, GCI score, and MRI parameters (global and regional at-rophy / iron-deposition) from V6 to V7 comparing placebo- vs. verum-treated patients, to identify possible symptomatic effects.
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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 | 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.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 | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | |
E.8.9.1 | In the Member State concerned months | 32 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 29 |