A Randomized, Blinded, Placebo-Controlled, Phase 1 Single Ascending Dose Study in Healthy Adult Male Volunteers and an Open-Label Multiple Ascending Dose Study in Pediatric SMA Participants Previously Treated with Onasemnogene Abeparvovec (Zolgensma*) to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB115
- Conditions
- SMASpinal muscular atrophy10029317
- Registration Number
- NL-OMON53796
- Lead Sponsor
- Biogen Idec Research Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 42
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Incidence of AEs/ SAEs</p><br>
- Secondary Outcome Measures
Name Time Method <p>Part A:<br /><br>• CSF BIIB115 concentration<br /><br>• CSF PK Parameters: t*<br /><br>• Serum BIIB115 concentration<br /><br>• Serum PK parameters: t*, AUC0-last, AUC*, Cmax, Tmax<br /><br><br /><br>Part B:<br /><br>1. Concentration of BIIB115 in Cerebral Spinal Fluid (CSF)<br /><br>2. Concentration of BIIB115 in Serum<br /><br>3. Terminal Elimination Half-Life (t*) of BIIB115 in Serum<br /><br>4. Area Under the Concentration-Time Curve from Time 0 to Last<br /><br>Measurable Concentration (AUC0-last) of BIIB115 in Serum<br /><br>5. Area Under the Concentration-Time Curve from Time 0 to Infinity<br /><br>(AUCinf) of BIIB115 in Serum<br /><br>6. Maximum Observed Concentration (Cmax) of BIIB115 in Serum<br /><br>7. Time to Reach Maximum Observed Concentration (Tmax) of BIIB115<br /><br>in Serum</p><br>