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

Biogen

Status and phase: Enrolling; Phase 1

Conditions: Muscular Atrophy, Spinal; Healthy Volunteer

Treatments: Drug: BIIB115-Matching Placebo; Drug: BIIB115

Study type: Interventional

Funder types: Industry

Identifiers

NCT05575011

277HV101

2022-000956-12 (EudraCT Number)

Details and patient eligibility

About

In this study, researchers will learn about a study drug called BIIB115 in healthy 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 more 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 more 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 treatment and follow up period will last for 13 months.
• Participants will have up to 6 clinic visits and 4 telephone calls.

During Part B:

• In Part B, children with SMA will receive BIIB115. Both researchers and participants will know they are receiving BIIB115.
• Participants will receive 2 total doses of BIIB115 given at 2 different times.
• The treatment and follow up period will last for 25 months.
• Participants will have up to 14 clinic visits and 6 telephone calls.

In both parts, participants will stay in the clinic for 24 hours after each dose for so that researchers can check on their health and any medical problems they might have.

Enrollment: 62 estimated patients

Sex: All

Ages: 6 months to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

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

Key Exclusion Criteria:

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

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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62 participants in 7 patient groups, including a placebo group

Part A: Cohort 1: BIIB115 Dose 1

Experimental group

Description:

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

Treatment:

Drug: BIIB115

Part A: Cohort 2: BIIB115 Dose 2

Experimental group

Description:

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

Treatment:

Drug: BIIB115

Part A: Cohort 3: BIIB115 Dose 3

Experimental group

Description:

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

Treatment:

Drug: BIIB115

Part A: Cohort 4: BIIB115 Dose 4

Experimental group

Description:

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

Treatment:

Drug: BIIB115

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

Placebo Comparator group

Description:

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

Treatment:

Drug: BIIB115-Matching Placebo

Part B: Cohort 5: BIIB115 Dose 3

Experimental group

Description:

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.

Treatment:

Drug: BIIB115

Part B: Cohort 6: BIIB115 Dose 4

Experimental group

Description:

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

Treatment:

Drug: BIIB115