SMA Spinal muscular atrophy
Conditions
Interventions
Part A:
Approximately 38 participants will be assigned to receive a single dose of
either BIIB115 (10 mg, 20 mg, 40 mg, or 80 mg) or placebo (6:2 ratio for Cohort
1
8:2 ratio for Cohorts 2 to 4).
Part B:
Approximately 24 children will be assigned to receive two doses of BIIB115 (up
to 40mg or up to 80 mg)
Sponsors
Biogen Idec Research Limited
Eligibility
Age
No minimum to 64 Years
Inclusion criteria
Inclusion criteria: Part A: 1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with applicable privacy regulations. 2. Males aged 18 to 55 years, inclusive, at the time of informed consent. 3. Have a body mass index of 18 to 30 kg/m2, inclusive. 4. All participants must practice highly effective contraception as described in Section 12.5 of the protocol. 5. Must be in good health as determined by the Investigator, based on medical history and Screening evaluations. Part B: - 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
Exclusion criteria
Exclusion criteria: Part A: 1. Any reason, anatomical or otherwise (including abnormal hematology/coagulation), that presents increase of risk of complication from multiple LP procedures required for dosing and CSF collection, per the investigator discretion. 2. History of any clinically significant cardiac, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal disease, or other major disease, as determined by the Investigator. 3. History of severe allergic or anaphylactic reactions, or of any allergic reactions that in the opinion of the Investigator are likely to be exacerbated by any component of the study treatment, including LP procedures. 4. History of, or ongoing malignancy, carcinoma in situ, or high-grade dysplasia (with the exception of no more than 1 basal cell carcinoma or squamous cell carcinoma that was completely excised and cured at least 12 months prior to randomization). Participants with cancers in remission for greater than 5 years prior to Day -1 may be included after discussion with the Sponsor. 5. Systolic blood pressure > 150 mmHg or < 90 mmHg after resting in a sitting position for at least 5 minutes at screening or prior to dosing. If out of range, testing may be repeated once at screening and once prior to dosing. 6. Clinically significant (as determined by the Investigator) 12-lead ECG abnormalities. 7. Confirmed demonstration of corrected QT interval, using Fridericia*s correction method, of > 450 ms. 8. Plans to undergo elective procedures or surgeries at any time after signing the ICF through the follow-up visit. 9. History of a suicide attempt within 5 years prior to screening or suicidal ideation in the past 6 months as indicated by a positive response (*Yes*) to either Question 4 or Question 5 of the Screening/Baseline version of the C-SSRS at screening. Participants with a history of a suicide attempt spanning more than 5 years should be evaluated by a mental health care practitioner before enrollment in the study. 10. History of, or positive test result at Screening for, HIV. 11. History of hepatitis C infection or positive test result at Screening for HCV antibody. 12. Current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or total hepatitis B core antibody [anti-HBc]). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive hepatitis B surface antibody [anti-HBs]) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti-HBs) are eligible to participate in the study. 13. Chronic, recurrent, or serious infection (e.g., pneumonia, septicemia), as determined by the Investigator, within 90 days prior to Screening or between Screening and Day -1 14. For the following parameters, if a participant has an out-of-range result that is not clinically significant (as determined by the Investigator), the test may be repeated once during the Screening period. The participant may be enrolled if the repeated result is within the reference range. • Any value for ALT, AST, bilirubin, or serum creatinine that is above the ULN at Screening or Baseline. • Any value of hemoglobin that is < 7.45 mmol/L (approx. < 12 g/dL) at Scre
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of AEs/ SAEs | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A: • CSF BIIB115 concentration • CSF PK Parameters: t* • Serum BIIB115 concentration • Serum PK parameters: t*, AUC0-last, AUC*, Cmax, Tmax Part B: 1. Concentration of BIIB115 in Cerebral Spinal Fluid (CSF) 2. Concentration of BIIB115 in Serum 3. Terminal Elimination Half-Life (t*) 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 | — |
Countries
Netherlands
Outcome results
None listed