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 | 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 efficacy of taldefgrobep alfa in participants who are already taking a stable dose of nusinersen or risdiplam or have a history of onasemnogene abeparvovec-xioi, compared to placebo, measured by change in the 32 item Motor Function Measure (MFM-32) total score between Baseline and Week 48 |
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E.2.2 | Secondary objectives of the trial |
- To compare the efficacy of taldefgrobep alfa to placebo using the Revised Upper Limb Module (RULM). -To compare the efficacy of taldefgrobep alfa to placebo using the Revised Hammersmith Scale (RHS). - To assess the safety and tolerability of taldefgrobep alfa as reflected byincluding change from baseline in lean body mass and bone mineral density on DXA scan at Week 48, Tanner staging for puberty monitoring, new or worsening lab abnormalities, injection acceptability assessments, treatment-related adverse events (AEs), serious AEs, and AEs leading to discontinuation. - To assess pharmacokinetic (PK) parameters of taldefgrobep as estimated with population PK modeling.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
● Spinal Muscular Atrophy confirmed by genetic diagnosis of 5qautosomal recessive SMA as well as SMN2 copy number ● Ambulant or non-ambulant ● Treated with an SMA disease-modifying therapy and anticipated to remain on that same treatment regimen and dose throughout the trial, including the following: i. a stable regimen of nusinersen for 6 months prior to Screening; and/or ii. a stable regimen of risdiplam, for 6 months prior to Screening; and/or iii. a single dose of onasemnogene abeparvovec, received at least 2 years prior to Screening. |
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E.4 | Principal exclusion criteria |
● Receiving or have received previous administration of anti-myostatin therapies ● Weight <15 kg ● Respiratory insufficiency, defined by the medical necessity for invasive or non-invasive ventilation for daytime treatment while awake (use overnight or during daytime naps is acceptable) ● History of spinal fusion or major surgeries within 6 months prior to screening or planned during the study. Non-surgical adjustments are allowed during the study (such as MAGEC rods). ● Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in the MFM-32 at Week 48
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Double blind phase: Baseline, visit 5, visit 6, visit 7, visit 8
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E.5.2 | Secondary end point(s) |
- Change from baseline in the RULM at Week 48 - Change from baseline in the RHS at Week 48 - Frequency of unique subjects with: new or worsening lab abnormalities, treatment related adverse events, serious adverse events, and adverse events leading to discontinuation.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Double blind phase: RULM: Baseline, visit 5, visit 6, visit 7, visit 8 RHS: Baseline, visit 5, visit 6, visit 7, visit 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) | 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 | 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 |
Double blind phase, followed by open-label extension phase |
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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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
United Kingdom |
United States |
Belgium |
Czechia |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
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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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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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 18 |