A Study to Learn About the Safety of BIIB115 Injections and How BIIB115 is Processed in the Bodies of Healthy Adult Male Volunteers and of Pediatric Participants With Spinal Muscular Atrophy Who Previously Took Onasemnogene Abeparvovec

NCT05575011 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 277HV1012022-000956-122023-505643-39
• Study Type: interventional
• Target: 62
• Locations: 9 countries
• Sites: 17

Brief Summary

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.

Conditions

Healthy Volunteer; Muscular Atrophy, Spinal

Outcome Measures

Primary Outcomes (1)

• 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.

  Part A: Up to Day 393, Part B: Up to Day 720; Part B LTE: Up to Day 2520

Secondary Outcomes (8)

• Parts A, B, and B LTE: Concentration of BIIB115 in Cerebral Spinal Fluid (CSF)

  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

  Day 1 to Day 180

• Parts A, B, and B LTE: Concentration of BIIB115 in Serum

  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

  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

  Part A: Day 1 to Day 180, Part B: Day 1 to Day 720

Study Arms (8)

Part A: Cohort 1: BIIB115 Dose 1

EXPERIMENTAL

Participants will receive a single dose of BIIB115, Dose 1, via IT bolus injection, on Day 1.

Drug: BIIB115

Part A: Cohort 2: BIIB115 Dose 2

EXPERIMENTAL

Participants will receive a single dose of BIIB115, Dose 2, via IT bolus injection, on Day 1.

Drug: BIIB115

Part A: Cohort 3:BIIB115 Dose 3

EXPERIMENTAL

Participants will receive a single dose of BIIB115, Dose 3, via IT bolus injection, on Day 1.

Drug: BIIB115

Part A: Cohort 4: BIIB115 Dose 4

EXPERIMENTAL

Participants will receive a single dose of BIIB115, Dose 4, via IT bolus injection, on Day 1.

Drug: BIIB115

Part A: Cohorts 1-4: BIIB115-Matching Placebo

PLACEBO COMPARATOR

Participants will receive a single dose of BIIB115-matching placebo, via IT bolus injection, on Day 1.

Drug: BIIB115-Matching Placebo

Part B: Cohort 5: BIIB115 Dose 3

EXPERIMENTAL

Pediatric SMA participants previously treated with onasemnogene abeparvovec will receive two doses of BIIB115, Dose 3, via IT bolus injection at two separate time points.

Drug: BIIB115

Part B: Cohort 6: BIIB115 Dose 4

EXPERIMENTAL

Pediatric SMA participants previously treated with onasemnogene abeparvovec will receive two doses of BIIB115, Dose 4, via IT bolus injectionat two separate time points.

Drug: BIIB115

Part B: Long Term Extension (LTE): BIIB115 Dose 4

EXPERIMENTAL

Pediatric SMA participants previously treated with onasemnogene abeparvovec who have completed Part B and are eligible will receive five doses of BIIB115, Dose 4, via IT bolus injection at separate time points for up to 60-month duration.

Drug: BIIB115

Interventions

BIIB115 DRUG

Administered as specified in the treatment arm

Part A: Cohort 1: BIIB115 Dose 1; Part A: Cohort 2: BIIB115 Dose 2; Part A: Cohort 3:BIIB115 Dose 3; Part A: Cohort 4: BIIB115 Dose 4; Part B: Cohort 5: BIIB115 Dose 3; Part B: Cohort 6: BIIB115 Dose 4; Part B: Long Term Extension (LTE): BIIB115 Dose 4

BIIB115-Matching Placebo DRUG

Administered as specified in the treatment arm

Part A: Cohorts 1-4: BIIB115-Matching Placebo

Eligibility Criteria

• Age: 6 Months - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Part A:
• Male healthy participants aged 18 to 55 years, inclusive
• Have a body mass index of 18 to 30 kilograms per meter square (kg/m\^2), inclusive
• 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 intravenous (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 B LTE
• Completion of the assessments in Part B
• Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is planned for study procedures (as assessed by the Investigator and either anesthesiologist or pulmonologist).

You may not qualify if:

• Part A:
• Any reason, anatomical or otherwise (including abnormal hematology/coagulation), that presents increase of risk of complication from multiple lumbar puncture (LP) procedures required for dosing and CSF collection, per the investigator discretion
• 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
• Chronic, recurrent, or serious infection, as determined by the investigator, within 90 days prior to screening or between screening and Day -1
• Current enrollment or a plan to enroll in any interventional clinical study of a drug, biologic, or device, in which an investigational treatment or approved therapy for investigational use is administered within 3 months (or 5 half-lives of the agent, whichever is longer) prior to randomization
• Part B:
• Severe or serious AEs related to onasemnogene abeparvovec therapy that are ongoing during Screening
• Interval of \<180 days between onasemnogene abeparvovec therapy and first BIIB115 dose
• Ongoing steroid treatment following onasemnogene abeparvovec at time of screening
• History of drug induced liver injury or liver failure per Hy's law definition
• History of thrombotic micrangiopathy
• Treatment with any SMN2-splicing modifier (nusinersen or risdiplam) after receiving onasemnogene abeparvovec. Treatment with nusinersen \<12 months from the first dose of BIIB115.
• Any reason, anatomical or otherwise (including abnormal hematology/coagulation), that presents increase of risk of complication from the LP procedures, CSF circulation, or safety assessments, including a history of hydrocephalus or implanted shunt for CSF drainage.
• Permanent ventilation, defined as tracheostomy or ≥16 hours ventilation /day continuously for \>21 days in the absence of an acute reversible event
• Part B LTE:

Sponsors & Collaborators

• Biogen: lead

Study Sites (17)

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Children's Hospital of Eastern Ontario

Ontario, K1H 8L1, Canada

Location

Hôpital Armand Trousseau

Paris, 75012, France

Location

Universitatsklinikum Essen

Essen, 45147, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Fondazione Serena Onlus - Centro Clinico Nemo

Milan, 20162, Italy

Location

Pediatric Neurology Unit, Catholic University

Rome, 00168, Italy

Location

Centre For Human Drug Research

Leiden, 2333, Netherlands

Location

UMC Utrecht

Utrecht, 3584 CX, Netherlands

Location

Instytut Centrum Zdrowia Matki Polki Dept of Neurology

Lodz, 93-338, Poland

Location

PRATIA S.A. MTZ Clinical Research Powered by Pratia

Warsaw, 02-172, Poland

Location

Instytut "Pomnik - Centrum Zdrowia Dziecka

Warsaw, 04-730, Poland

Location

Kyungpook National University Hospital

Daegu, 700-721, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Great Ormond Street Hospital for Children

Bloomsbury, WC1N 3JH, United Kingdom

Location

Sheffield Childrens Hospital

Sheffield, S10 2TH, United Kingdom

Location

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinded for Part A and open-label for Part B of the study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sequential for Parts A, B, and B LTE parallel for Cohorts 1-4 within Part A, parallel for Cohorts 5-6 within Part B

Study Record Dates

• First Submitted: October 7, 2022
• First Posted: October 12, 2022
• Study Start: October 10, 2022
• Primary Completion (Estimated): November 14, 2031
• Study Completion (Estimated): November 14, 2031
• Last Updated: July 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

IT (2); CA (1); DE (3); PL (3); NL (2); KR (2); GB (2); BE (1); FR (1)