E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Amyotrophic Lateral Sclerosis (ALS) |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10077024 |
E.1.2 | Term | Familial amyotrophic lateral sclerosis |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002026 |
E.1.2 | Term | Amyotrophic lateral sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 primary objective of the study is to evaluate the long-term safety and tolerability of BIIB067 in participants with ALS and confirmed superoxide dismutase 1 (SOD-1) mutation. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate the pharmacokinetic (PK), pharmacodynamic (PD) and efficacy of BIIB067 administered to subjects with ALS and confirmed SOD1 mutation. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Must have diagnosis of SOD1-ALS, and must have completed the End of Study Visit for either Parts A, B and/or C of Study 233AS101 (i.e., were not withdrawn). - If taking riluzole, must be receiving a stable dose for ≥30 days prior to Day 1 - For female participants of childbearing potential must agree to practice effective contraception during the study and for 5 months after their last dose of study treatment. - Medically able to undergo the study procedures, and to adhere to the visit schedule at the time of study entry, as determined by the Investigator. - Participants from Study 233AS101 Parts A and B must have a washout ≥16 weeks between the last dose of study treatment received in Study 233AS101 and the first dose of BIIB067 received in the current Study 233AS102. - If taking edaravone, participant must have initiated edaravone ≥ 60 days (2 treatment cycles) prior to Day 1. Edaravone may not be administered on dosing days. |
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria: - History of allergies to a broad range of anaesthetics. - Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally and could place a participant at an increased risk for bleeding during or after an LP procedure. These risks could include, but are not limited to, anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities) and underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, Von Willebrand’s disease, liver disease). - Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter. - Prior or current treatment with small interfering ribonucleic acid (RNA), stem cell therapy, or gene therapy. - Treatment with another investigational drug, biological agent (excluding BIIB067), or device within 1 month or 5 half-lives of study agent, whichever is longer. - Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system (DPS) during the study period. - Female subjects who are pregnant or currently breastfeeding. - Current enrollment in any other interventional study. - Current or recent (within 1 month) use, or anticipated need, in the opinion of the Investigator, of copper (II) (diacetyl-bis (N4-methylthiosemicarbazone)) or pyrimethamine.
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 experiencing 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) |
- Levels of BIIB067 in Plasma - Levels of BIIB067 in Cerebral Spinal Fluid (CSF) - Change from baseline in Total SOD1 Protein in CSF - Change from Baseline in Neurofilament Light Chain (NfL) Concentration in Plasma - Change from Baseline in ALS Functional Rating Scale - Revised (ALSFRS-R) Score - Change from Baseline in Slow Vital Capacity (SVC) - Change from Baseline in Handheld Dynamometry (HHD) MegaScore and Individual Muscle Strength - Time to death or Permanent Ventilation - Time to death
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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 | 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 | 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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
New Zealand |
Australia |
Canada |
Israel |
Japan |
United Kingdom |
United States |
European Union |
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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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The end of study is last participant, last visit (approximately 4 weeks after their last dose). The last Maintenance Dose Visit for a participant will occur when the last participant enrolled has had the opportunity to have their Week 152 Maintenance Dose Visit |
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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 | 3 |
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 | 7 |
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 | 7 |