E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | Spinal Muscular Atrophy (SMA) | |
E.1.1.1 | Medical condition in easily understood language | Spinal Muscular Atrophy (SMA) | |
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 | E.1.2 | Level | LLT | E.1.2 | Classification code | 10041583 | E.1.2 | Term | Spinal muscular atrophy, unspecified | E.1.2 | System Organ Class | 100000004850 | |
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 | Evaluate the long-term safety and tolerability of apitegromab in patients with Type 2 and Type 3 SMA | |
E.2.2 | Secondary objectives of the trial | Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points Further evaluate the immunogenicity of apitegromab | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | 1. Informed consent document signed by the patient if the patient is legally an adult. If the patient is legally a minor, informed consent document signed by the patient’s parent or legal guardian and patient’s oral or written assent obtained, if applicable and in accordance with the regulatory and legal requirements of the participating location. 2. Patients who have completed the Phase 2 TOPAZ (Study SRK-015-002) trial or the Phase 3 SAPPHIRE (Study SRK-015-003) trial. 3. Estimated life expectancy >2 years from Baseline (Day 1). 4. Able to receive study drug infusions and provide blood samples through the use of a peripheral IV or a long-term IV access device that the patient has placed for reasons independent from the trial (i.e., for background medical care and not for the purpose of receiving apitegromab in the trial), throughout the trial. 5. Able to adhere to the requirements of the protocol. 6. Females of childbearing potential must have a negative pregnancy test at Baseline and agree to use at least 1 acceptable method of contraception throughout the trial and for 20 weeks after the last dose of apitegromab. Female patients who are expected to have reached reproductive maturity by the end of the trial must agree to adhere to trial-specific contraception requirements. | |
E.4 | Principal exclusion criteria | 1. Patient permanently discontinued study treatment during the feeder trial (i.e., TOPAZ or SAPPHIRE). 2. Nutritional status that was not stable over the past 6 months and is not anticipated to be stable throughout the trial or medical necessity for a gastric/nasogastric feeding tube, where the majority of feeds are given by this route, as assessed by the investigator. 3. Patient is currently enrolled in any investigational drug trial other than TOPAZ or SAPPHIRE. 4. Prior history of severe hypersensitivity reaction or intolerance to SMN-targeted therapies. 5. Prior history of severe hypersensitivity reaction or intolerance to apitegromab. 6. Use of chronic daytime noninvasive ventilatory support for >16 hours daily in the 2 weeks before dosing, or anticipated to regularly receive such daytime ventilator support chronically throughout the trial. 7. Any acute or comorbid condition interfering with the well-being of the patient at the patient’s last visit in TOPAZ or SAPPHIRE, including active systemic infection, the need for acute treatment, or inpatient observation due to any reason. 8. Pregnant or breastfeeding. 9. Any other condition or clinically significant laboratory result or ECG value that, in the opinion of the Investigator, may compromise safety or compliance, would preclude the patient from successful completion of the trial, or interfere with the interpretation of the results. | |
E.5 End points |
E.5.1 | Primary end point(s) | Incidence of TEAEs and SAEs by severity | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | Evaluted at timepoints as described in the protocol | |
E.5.2 | Secondary end point(s) | - HFMSE total score at prespecified time points (excludes TOPAZ Cohort 1 patients) - RULM total score at prespecified time points (excludes TOPAZ Cohort 1 patients) - Number of WHO motor development milestones attained at prespecified time points (excludes TOPAZ Cohort 1 patients) - RHS total score and results for 6-Minute Walk Test, 30-Second Sit-to-Stand, 10-Meter Walk/Run (from the RHS), and timed rise from floor (from the RHS) at prespecified time points (TOPAZ Cohort 1 patients only) | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | Evaluted at timepoints as described in the protocol | |
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 | 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 | Immunogenicity, tolerability | |
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 | 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 | 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 | 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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 States | France | Poland | Netherlands | Spain | Germany | Italy | Belgium | United Kingdom | |
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 | |
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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |