In this study, researchers will learn about a study drug called BIIB115 in healthy adult male volunteers and in participants with spinal muscular atrophy (SMA). This study will focus on children with SMA. The main objective of the study is to learn about the safety of BIIB115 and how participants respond to different doses of BIIB115. The main question researchers want to answer is: • How many participants have adverse events and serious adverse events during the study? Adverse events are unwanted health problems that may or may not be caused by the study drug. Researchers will also learn about how the body processes BIIB115. They will do this by measuring the levels of BIIB115 in both the blood and the cerebrospinal fluid, also known as the CSF. This is the fluid around the brain and spinal cord. The study will be split into 2 parts - Part A and Part B. During Part A: * After screening, healthy volunteers will be randomly placed into 1 of 4 groups to receive either BIIB115 or a placebo. A placebo looks like the study drug but contains no real medicine. * Participants will receive a single dose of either BIIB115 or the placebo as an injection directly into the spinal canal on Day 1. * Neither the researchers nor the participants will know if the participants will receive BIIB115 or the placebo. * The Part A treatment and follow-up period will last for 13 months. * Participants will have up to 6 clinic visits and 4 phone calls. During Part B: * After screening, children with SMA will be placed into 1 of 2 groups to receive BIIB115. * The doses of each group will be decided based on the results of Part A. * Both researchers and participants will know they are receiving BIIB115. * Participants will first receive 2 total doses of BIIB115 given at 2 different times. * The Part B treatment and follow-up period will last for 24 months. * Participants will have up to 14 clinic visits and 6 phone calls. Part B Long-Term Extension: * After completing the 25 months in Part B, participants may move onto the long-term extension (LTE). * They will receive 5 more doses of BIIB115 at different times. * The Part B LTE treatment and follow-up will last for 60 months. * Participants will have up to 12 more clinic visits and 19 phone calls. In both Part A and Part B, participants will stay in the clinic for 24 hours after each dose so that researchers can check on their health. This 24-hour stay will not be required for the Part B LTE period.
The primary objective of the study is to assess the safety and tolerability of BIIB115 administered via intrathecal (IT) bolus injection to healthy participants in Part A, pediatric participants with spinal muscular atrophy who have previously received onasemnogene abeparvovec in Part B, and to participants who complete Part B in Part B LTE. The secondary objectives of the study is to evaluate the pharmacokinetics (PK) of BIIB115 in Parts A, B, and B LTE.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
62
Administered as specified in the treatment arm
Administered as specified in the treatment arm
Universitair Ziekenhuis Gent
Ghent, Belgium
Children's Hospital of Eastern Ontario
Ontario, Canada
Hôpital Armand Trousseau
Paris, France
Universitatsklinikum Essen
Essen, Germany
Universitaetsklinikum Freiburg
Freiburg im Breisgau, Germany
Universitaetsklinikum Heidelberg
Heidelberg, Germany
Fondazione Serena Onlus - Centro Clinico Nemo
Milan, Italy
Pediatric Neurology Unit, Catholic University
Rome, Italy
Centre For Human Drug Research
Leiden, Netherlands
UMC Utrecht
Utrecht, Netherlands
...and 7 more locations
Parts A, B, and B Long Term Extension (LTE): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or is a medically important event.
Time frame: Part A: Up to Day 393, Part B: Up to Day 720; Part B LTE: Up to Day 2520
Parts A, B, and B LTE: Concentration of BIIB115 in Cerebral Spinal Fluid (CSF)
Time frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720; Part B LTE: Day 720 to Day 2520
Part A: Terminal Elimination Half-Life (t½) of BIIB115 in CSF
Time frame: Day 1 to Day 180
Parts A, B, and B LTE: Concentration of BIIB115 in Serum
Time frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720; Part B LTE: Day 720 to Day 2520
Parts A and B: Terminal Elimination Half-Life (t½) of BIIB115 in Serum
Time frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
Parts A and B: Area Under the Concentration-Time Curve from Time 0 to Last Measurable Concentration (AUC0-last) of BIIB115 in Serum
Time frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
Parts A and B: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of BIIB115 in Serum
Time frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
Parts A and B: Maximum Observed Concentration (Cmax) of BIIB115 in Serum
Time frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
Parts A and B: Time to Reach Maximum Observed Concentration (Tmax) of BIIB115 in Serum
Time frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.