Amyotrophic Lateral Sclerosis (ALS) MedDRA version: 20.0 Level: PT Classification code 10077024 Term: Familial amyotrophic lateral sclerosis System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: PT Classification code 10052653 Term: Amyotrophic lateral sclerosis gene carrier System Organ Class: 1
Conditions
Interventions
Product Code: BIIB067 (ISIS666853)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: tofersen
CAS Number: 2088232-70-4
Current Sponsor code: BIIB067 (ISIS 666853)
Other descriptive nam
Sponsors
Biogen Idec Research Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key Part A Inclusion Criteria: - Participants should have a protocol-defined rapidly progressive SOD1 mutation, confirmed by a central reader, or a SOD1 mutation that is adjudicated for inclusion by an external mutation adjudication committee. - Participants with plasma NfL level less than the protocol-defined threshold. - Participants who are clinically presymptomatic for ALS (i.e., must not have clinically manifested ALS). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 105 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: Key Part A Exclusion Criteria: - History or positive test result at screening for human immunodeficiency virus (HIV). The requirement for testing at Screening may be omitted if it is not permitted by local regulations. - Current hepatitis C infection (defined as positive Hepatitis C Virus (HCV) antibody and detectable HCV RNA). Participants with positive HCV antibody and undetectable HCV Ribonucleic Acid (RNA) are eligible to participate in the study (United States Centers for Disease Control and Prevention). - Current hepatitis B infection (defined as positive for hepatitis B surface antigen (HBsAg) and/or anti-Hepatitis B Core antibody (HBc)). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive anti-hepatitis B surface antibody (HBs) or vaccination (defined asnegative HBsAg, negative anti-HBc, and positive anti- HBs) are eligible to participate in the study. - History of systemic hypersensitivity reaction to tofersen, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study. - History of confounding neuromuscular or neurological disorder that is expected to have a progressive (i.e., worsening) course during the study, and/or is expected to be associated with elevations in NF, in the opinion of the Investigator. - Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that if not managed optimally could place a participant at an increased risk for intraoperative or postoperative bleeding. - Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression = 90 days of Screening, which in the opinion of the Investigator would interfere with the study procedures. - Anticipated need, in the opinion of the Investigator, for administration of any antiplatelet or anticoagulant medication (e.g., clopidogrel) that cannot be safely continued or held for an LP procedure, if necessary, according to local or institutional guidelines and/or Investigator determination. - Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs), biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering RNA, stem cell therapy, or gene therapy is allowed. - Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment, biological agent, device, or approved therapy for investigational use. Participation in a noninterventional study focused on ALS natural history may be allowed at the discretion of the Investigator. NOTE: Other protocol defined Inclusion/Exclusion criteria will apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the efficacy of BIIB067 when initiated in presymptomatic adult carriers of a superoxide dismutase 1 (SOD1) mutation with elevated neurofilament (NF). ;Secondary Objective: The secondary objectives of this study are to evaluate the safety and tolerability of BIIB067 and to evaluate the effect of BIIB067 on pharmacodynamics (PD)/treatment response biomarkers.;Primary end point(s): Parts B and C: Percentage of Participants with Emergence of Clinically Manifested ALS Within 12 Months of Part B Baseline ;Timepoint(s) of evaluation of this end point: Up to 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Parts B and C: Percentage of Participants with Emergence of Clinically Manifested ALS Within 2 Years of Part B Baseline 2. Parts B and C: Time to Emergence of Clinically Manifested ALS 3. Parts B and C: Change in Revised ALS Functional Rating Scale (ALSFRS-R) Total Score 4. Parts B and C: Change from Baseline in Percent Predicted Slow Vital Capacity (SVC) 5. Parts B and C: Percentage of Participants with Ventilation Assistance-free Survival (VAFS) 6. Parts B and C: Percentage of Participants with Overall Survival 7. Parts B, C and D: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during the Treatment Period 8. Parts B, C and D: Change from Baseline in Plasma NfL Concentrations 9. Parts B, C and D: Change in Total Cerebrospinal Fluid (CFL) SOD1 Concentrations;Timepoint(s) of evaluation of this end point: Part B, C and D: Up to 2 years | — |
Countries
Australia, Belgium, Brazil, Bulgaria, Canada, France, Germany, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactMedical Director
Biogen
Outcome results
None listed