Healthy VolunteerPhase 1NCT05575011
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
A Phase 1 study testing BIIB115 in people with Healthy Volunteer and Muscular Atrophy, Spinal, run by Biogen at 16 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteer, Muscular Atrophy, Spinal
- What is being tested?
- BIIB115
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 16 sitesin 9 countries
- Study dates
- 10 Oct 2022to 14 Nov 2031
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 55 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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
Show all 15Show fewer
- 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).
Who cannot join
- 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:
Show all 19Show fewer
- 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:
- Any new condition or worsening of an existing condition that, according to the Investigator, would make the participant unsuitable for inclusion, could interfere with the assessment of safety, or would compromise the ability of the participant to undergo study procedures.
- Clinically significant abnormalities in hematology, blood chemistry parameters, or electrocardiograms (ECGs) prior to first LTE visit that would make the participant unsuitable for inclusion as assessed by the Investigator.
- Treatment with an approved SMN2-splicing modifier (nusinersen or risdiplam).
- NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
16 sites in 9 countries.
16 sites in 9 countries
Germany3 sites
Universitatsklinikum Essen
Essen, 45147
Universitaetsklinikum Freiburg
Freiburg im Breisgau, 79106
Universitaetsklinikum Heidelberg
Heidelberg, 69120
Poland3 sites
Instytut Centrum Zdrowia Matki Polki Dept of Neurology
Lodz, 93-338
PRATIA S.A. MTZ Clinical Research Powered by Pratia
Warsaw, 02-172
Instytut "Pomnik - Centrum Zdrowia Dziecka
Warsaw, 04-730
Italy2 sites
Fondazione Serena Onlus - Centro Clinico Nemo
Milan, 20162
Pediatric Neurology Unit, Catholic University
Rome, 00168
Netherlands2 sites
Centre For Human Drug Research
Leiden, 2333
UMC Utrecht
Utrecht, 3584 CX
United Kingdom2 sites
Great Ormond Street Hospital for Children
Bloomsbury, WC1N 3JH
Sheffield Childrens Hospital
Sheffield, S10 2TH
About this study
Official title: A Randomized, Blinded, Placebo-Controlled, Phase 1 Single Ascending Dose Study in Healthy Adult Male Volunteers and an Open-Label Multiple Ascending Dose Study With Long-Term Extension in Pediatric SMA Participants Previously Treated With Onasemnogene Abeparvovec (Zolgensma™) to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB115
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:
Read more
- 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.
Read the detailed description
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.
- Conditions
- Healthy Volunteer, Muscular Atrophy, Spinal
- Being tested
- BIIB115, BIIB115-Matching Placebo
- Medical subject headings
- Muscular Atrophy, Spinal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIIB115Drug
Administered as specified in the treatment arm
BIIB115-Matching PlaceboDrug
Administered as specified in the treatment arm
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: BIIB115 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: 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
Measured: Day 1 to Day 180
Parts A, B, and B LTE: Concentration of BIIB115 in Serum
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2022
- Study start10 Oct 2022
- Primary completion14 Nov 2031 (estimated)
- Study completion14 Nov 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteerStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Sequential for Parts A, B, and B LTE parallel for Cohorts 1-4 within Part A, parallel for Cohorts 5-6 within Part B
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05575011
- Sponsor's protocol ID
- 277HV101
- Other IDs
- 2022-000956-12, 2023-505643-39, 2023
- Status last verified
- Oct 2026
- First submitted
- 7 Oct 2022
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/