E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Proximal spinal muscular atrophy (SMA) is characterized by weakness of predominantly axial and proximal muscle groups and is caused by homozygous deletion of the survival motor neuron 1 (SMN1)-gene. There are 4 SMA types (type 1-4), with a descending order of severity. Age at onset and achieved motor milestones are the characteristics to define severity. Treatment of SMA is exclusively supportive. |
Spinale spieratrofie (SMA) is een aandoening gekenmerkt door proximale spierzwakte door degeneratie van motorneuronen in de voorhoorncellen van het ruggenmerg. SMA wordt veroorzaakt door een homzygote deletie van het SMN1-gen. Er zijn 4 types SMA, geclassificeerd op basis van behaalde motorische mijlpalen en leeftijd van eerste symtpomen. De behandeling van SMA is ondersteunend. |
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E.1.1.1 | Medical condition in easily understood language |
Spinal muscular atrophy (SMA) is a disorder characterized by muscle weakness caused by loss of motor cells of the spinal cord. SMA is a genentic disease. Treatment of SMA is supportive. |
Spinale spieratrofie (SMA) is een aandoening met proximale spierzwakte door verlies van motorische cellen in het ruggenmerg. SMA is een genetische aandoening. De behandeling van SMA is ondersteunend. |
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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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068209 |
E.1.2 | Term | Spinal muscular atrophy adult onset |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051203 |
E.1.2 | Term | Spinal muscular atrophy congenital |
E.1.2 | System Organ Class | 100000004850 |
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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 |
The main objective of this placebo-controlled cross-over trial in adult patients with SMA type 2, 3 and 4 is to investigate the effect and efficacy of pyridostigmine on muscle strength and fatiquabillity in patients with SMA. |
Het hoofddoel van deze placebo-controlled cross-over trial bij volwassen patienten met SMA type 2, 3 en 4 is het onderzoeken van effect en doeltreffendheid van pyridostigmine op de spierkracht en het uithoudingsvermogen bij patiënten met SMA. |
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E.2.2 | Secondary objectives of the trial |
Secondary outcome measures are the effect of pyridostigmine on neurofysiologic parameters and subjective scales |
Secundaire doelen van deze studies zijn het effect van pyridostigmine op neurofysiologische parameters en subjectieve scorelijsten. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with SMA will be included following the predefined criteria: 1) a clinical diagnosis of SMA type 2, 3a, 3b or 4 and a genetically confirmed homozygous SMN1 deletion 2) ability to complete visits during trial period; 3) given oral and written informed consent when ≥18 years old; 4) given informed consent by the parents or legal representative in case of patients aged <18 years old; 5) ability of performing the Nine Hole Peg test within 50 seconds |
1) diagnose SMA type 2, 3a, 3b of 4 op basis van het klinisch beeld en bevestigd met een homozygote deletie van het SMN1-gen; 2) mogelijkheid tot het afleggen van alle visits en procedures gedurende de trialperiode; 3) schriftelijk en mondeling informed consent ≥18 jaar leeftijd; 4) schriftelijk en mondeling informed consent door ouders en/of voogd bij <18 jaar leeftijd; 5) Nine Hole Peg test binnen 50 seconden
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E.4 | Principal exclusion criteria |
Exclusion criteria for patients are 1) known concomitant disorders of the NMJ (Lambert Eaton myasthenic syndrome, myasthenia gravis); 2) use of drugs that may alter NMJ function; 3) SMA type 1; 4) apprehension against participation in EMG; 5) inability to meet study visits; 6) mechanical gastro-intestinal, urinary or biliary obstruction; 6) clinical significant alterations of laboratory tests (electrolytes, liver function, kidney function, thyroid function or blood dysplasia) drawn within 14 days prior to start of study entry; 7) electrocardiofysiology abnormalities known as a contraindication for pyridostigmine use; 8) pregnancy 9) allergy to bromides 10) bronchial astma |
1) bewezen aandoening van de neuromusculaire overgang (lambert eaton myastheen syndroom, myasthenia gravis) naast SMA; 2) gebruik van medicatie die de neuromusculaire overgang beïnvloeden; 3) SMA type 1; 4) weerstand tegen het ondergaan van repetitieve zenuwstimualtie; 5) onvermogen tot afleggen van alle visits; 6) mechanicshe obstructie gastro-intestinaal, urogenitaal of galwegen; 7) klinisch significante laboratoriumveranderingen (elektrolyten, leverfunctie, nierfunctie, schildklierfucntie of bloedbeeld); 7) afwijkend elektrocardiogram; 8) zwangerschap; 9) allergie voor bromiden; 10) bronchiale astma |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in Nine Hole Peg test and Motor Function Measure |
Verandering in Nine Hole Peg test and Motor Function Measure |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients will be screened. Clinical evaluation in patients will take place 2 times in de treatmentperiod of 8 weeks; at te start and at the end. |
Patienten worden gescreend. Tijdens de 8weekse- behandelperiode worden patienten op twee tijdsstippen ge-evalueerd, aan het begin (week1) en aan het eind (week 8) |
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E.5.2 | Secondary end point(s) |
Secondary outcome measures are scores on Vigori Measurement, scales on daily activities and presence of decrement upon repetitive nerve stimulation, quality of and activity in life scores, and adverse events. |
Secundaire uitkomsten zijn veranderingen in de uitkomst van de Vigori Meter, MRC sumscore, scorelijsten over dagelijkse activiteiten, de aanwezigheid en verandering in decrementie bij repetitieve zenuwstimulatie en bijwerkingen. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Clinical evaluation in patients will take place 2 times in de treatmentperiod of 8 weeks; at te start and at the end. |
Tijdens de 8weekse- behandelperiode worden patienten op twee tijdsstippen ge-evalueerd, aan het begin (week1) en aan het eind (week 8) |
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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) | 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 | 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 | Yes |
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
| 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 | No |
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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Last visit of last subject undergoing the trial |
Laatste bezoek van laatste participerende patient |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |