E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients suffereing from Amytrophic Lateral 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.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate efficacy and safety of the combination therapy penicilline G / Hydrocortisone in ALS patients |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients must be over 18 years of age.
2. Patients diagnosed with laboratory supported, clinically probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria (Brooks, 1994).
3. Disease duration from symptoms onset no longer than 24 months at the screening visit.
4. Patient with a FVC (Forced Vital Capacity) equal to or more than 80% predicted normal value for gender, height, and age at the screening visit
5. Patients must have bulbar involvement (defined as clinically evident dysarthria or a ≥1 point drop on questions 1-3 of the revised version of the ALS functional rating scale (ALS-FRS-R).
6. Patient treated with a stable dose of riluzole (100 mg/day) for at least 30 days prior to screening.
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E.4 | Principal exclusion criteria |
1. Patients with concomitant frontotemporal dementia (FTD).
2. Patients on non-invasive ventilation (NIV) or who underwent tracheotomy.
3. Patients with syphilis or a medical history of syphilis.
4. Patients with known penicillin allergy or patients with a positive penicillin allergy skin test.
5. Patients with a contra-indication for using penicillin (use of methotrexate, renal insufficiency).
6. Patients with a medical history of epilepsy.
7. Patients with a contra-indication for using hydrocortisone (uncontrolled hypertension or diabetes mellitus, ulcus ventriculi or ulcus duodeni, patients with acute infections)
8. In the case of a female with childbearing potential, the patient must not be pregnant or breast-feeding. Women of childbearing potential should use adequate contraception.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to week 45 in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change from baseline to Week 45. |
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E.5.2 | Secondary end point(s) |
1. Survival defined as the time from randomization to the date of documented death or date of tracheotomy.
2. Change of slow Vital Capacity (sVC) from baseline to each time point (week 3, 11, 15, 23, 27, 35, 39 and 45).
3. Change in muscle strength from baseline to each time point
4. Change in plasma creatine level from baseline to each time point.
5. Time to next stage of the King’s staging system.
6. Time to gastrostomy defined as the time from randomization to the time of the gastrostomy.
7. Changes in score on the EQ-5D-5L. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Survival defined as the time from randomization to the date of documented death or date of tracheotomy.
2. Change of slow Vital Capacity (sVC) from baseline to each time point (week 3, 11, 15, 23, 27, 35, 39 and 45).
3. Change in muscle strength from baseline to each time point
4. Change in plasma creatine level from baseline to each time point.
5. Time to next stage of the King’s staging system.
6. Time to gastrostomy defined as the time from randomization to the time of the gastrostomy.
7. Changes in score on the EQ-5D-5L.
8. Safety: Number of Serious Adverse Events (SAEs), changes on clinical examination including vital signs and weight, laboratory exams (biochemistry and hematology).
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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 | 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) | 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 | 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 | 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 | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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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LVLS, or any earlier if DSMB advises to prematurely stop 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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |