E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
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 evaluate the safety and tolerability of multiple ascending doses of BIIB115 administered via IT bolus injection participants with SMA who previously received onasemnogene abeparvovec |
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E.2.2 | Secondary objectives of the trial |
To evaluate the PK of multiple ascending doses of BIIB115 administered via IT bolus injection to pediatric SMA participants who previously received onasemnogene abeparvovec |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age 0.5 to 12 years old, inclusive, at the time of informed consent - Weight ≥7 kg at the time of informed consent - Genetic diagnosis of SMA (5q SMA homozygous survival motor neuron 1 (SMN1)gene deletion or mutation or compound heterozygous mutation)- Survival motor neuron 2 (SMN2) copy number ≥1 - Must have received IV onasemnogene abeparvovec per the approved label or per guidelines including the steroid regimen and monitoring specified therein - Treatment with onasemnogene abeparvovec ≥180 days prior to first BIIB115 dose - Potential for improvement due to suboptimal clinical status secondary to SMA, as determined by the Investigator |
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E.4 | Principal exclusion criteria |
- Severe or serious AEs related to onasemnogene abeparvovec therapy that are ongoing during Screening - Interval of <180 days between onasemnogene abeparvovec therapy and first BIIB115 dose - Ongoing steroid treatment following onasemnogene abeparvovec at time of screening - History of drug induced liver injury or liver failure per Hy's law definition - History of thrombotic micrangiopathy - Treatment with any SMN2-splicing modifier (nusinersen or risdiplam) after receiving onasemnogene abeparvovec. Treatment with nusinersen <12 months from the first dose of BIIB115. - Any reason, anatomical or otherwise (including abnormal hematology/coagulation),that presents increase of risk of complication from the LP procedures, CSF circulation, or safety assessments, including a history of hydrocephalus or implanted shunt for CSF drainage - Permanent ventilation, defined as tracheostomy or ≥16 hours ventilation/day continuously for ≥21 days in the absence of an acute reversible event
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) |
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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) |
1. Concentration of BIIB115 in Cerebral Spinal Fluid (CSF) 2. Concentration of BIIB115 in Serum 3. Terminal Elimination Half-Life (t½) of BIIB115 in Serum 4. Area Under the Concentration-Time Curve from Time 0 to Last Measurable Concentration (AUC0-last) of BIIB115 in Serum 5. Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of BIIB115 in Serum 6. Maximum Observed Concentration (Cmax) of BIIB115 in Serum 7. Time to Reach Maximum Observed Concentration (Tmax) of BIIB115 in Serum |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Days 1 and 360 2. Day 1 to Day 720 3. Day 1 to Day 720 4. Day 1 to Day 720 5. Day 1 to Day 720 6. Day 1 to Day 720 7. Day 1 to Day 720 |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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 | No |
E.8.1.7 | Other | Yes |
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 | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 |
Israel |
United Kingdom |
Belgium |
France |
Germany |
Italy |
Netherlands |
Poland |
Portugal |
Spain |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 3 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 3 |