E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Spinal Muscular Atrophy (SMA) |
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E.1.1.1 | Medical condition in easily understood language |
Spinal Muscular Atrophy (SMA) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041582 |
E.1.2 | Term | Spinal muscular atrophy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 examine the clinical efficacy of ISIS 396443 administered intrathecally to patients with infantile-onset SMA. |
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E.2.2 | Secondary objectives of the trial |
To examine the safety and tolerability of ISIS 396443 administered intrathecally to patients with infantile-onset SMA. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
∙ Be 7 months (210 days) of age or younger at screening
∙ Be born between 37 and 42 weeks
∙ Be medically diagnosed with spinal muscular atrophy (SMA) and have SMN2 Copy # of 2
∙ Be able to follow all study procedures
∙ Reside within 9 hours ground travel each way, for the duration of the study
∙ Meet additional study-related criteria
. Body weight ≥ 3rd percentile for age using appropriate country-specific guidelines
. Genetic documentation of 5q SMA homozygous gene deletion, homozygous mutation, or compound heterozygote |
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E.4 | Principal exclusion criteria |
. Hypoxemia (O2 saturation awake <96% or O2 saturation asleep <96%, without ventilation support) during screening evaluation
. Signs or symptoms of SMA present at birth or within the first week after birth
.Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period
.History of brain or spinal cord disease that would interfere with the LP procedures, CSF circulation, or safety assessments
.Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter
.Subject’s caregiver is not willing to continue to meet standard of care guidelines for care (including vaccinations and RSV prophylaxis if available), nutritional and respiratory support throughout the duration of the study
.Clinically significant abnormalities in hematology or clinical chemistry parameters, as assessed by the Site Investigator, at screening that would render the subject unsuitable for inclusion |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to death or permanent ventilation [≥16 hours ventilation/day continuously for >21 days in the absence of an acute reversible event OR tracheostomy] |
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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) |
• Change from baseline in CHOP-INTEND infant motor function scale at 13 months
• Change from baseline in motor milestones at 13 months
• Percent of subjects not requiring permanent ventilation over 13 months
• Survival rate over 13 months
• Time to death or permanent ventilation in the subgroups of subjects below the study median disease duration
• Time to death or permanent ventilation in the subgroups of subjects above the study median disease duration |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
Sham-Procedure Controlled |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 |
Australia |
Canada |
France |
Germany |
Hong Kong |
Italy |
Japan |
Korea, Republic of |
Spain |
Sweden |
Taiwan |
United Kingdom |
United States |
|
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 | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |