Clinical trial NCT05575011: A Study to Learn About the Safety of Salanersen (BIIB115) Injections and How Salanersen is Processed in the Bodies of Healthy Adult Male Volunteers and of Pediatric Participants With Spinal Muscular Atrophy Who Previously Took Onasemnogene Abeparvovec
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 in Pediatric SMA Participants Previously Treated With Onasemnogene Abeparvovec (Zolgensma™) to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB115
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteer
Muscular Atrophy, Spinal
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2022-10-12
Enrollment: 62
Sex: ALL
Minimum age (years): 6
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Sequential for Parts A and B, parallel for Cohorts 1-4 within Part A, parallel for Cohorts 5-6 within Part B
Primary purpose: TREATMENT

Brief summary: In this study, researchers will learn about a study drug called salanersen (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 salanersen and how participants respond to different doses of salanersen. 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 salanersen. They will do this by measuring the levels of salanersen 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 salanersen or a placebo. A placebo looks like the study drug but contains no real medicine.
* Participants will receive a single dose of either salanersen 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 salanersen 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 salanersen. Both researchers and participants will know they are receiving salanersen.
* Participants will receive 2 total doses of salanersen 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.


Eligibility 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 salanersen 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 salanersen 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 salanersen.
* 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.

Primary outcomes:
measure: Parts A and B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Part A: Up to Day 393, Part B: Up to Day 720
Secondary outcomes:
measure: Parts A and B: Concentration of Salanersen in Cerebral Spinal Fluid (CSF)
timeFrame: Part A: Day 1 to Day 180, Part B: Days 1 and 360
measure: Part A: Terminal Elimination Half-Life (t½) of Salanersen in CSF
timeFrame: Day 1 to Day 180
measure: Parts A and B: Concentration of Salanersen in Serum
timeFrame: Part A: Day 1 to Day 180, Part B: Day 1 to 720
measure: Parts A and B: Terminal Elimination Half-Life (t½) of Salanersen in Serum
timeFrame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
measure: Parts A and B: Area Under the Concentration-Time Curve from Time 0 to Last Measurable Concentration (AUC0-last) of Salanersen in Serum
timeFrame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
measure: Parts A and B: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of Salanersen in Serum
timeFrame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
measure: Parts A and B: Maximum Observed Concentration (Cmax) of Salanersen in Serum
timeFrame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
measure: Parts A and B: Time to Reach Maximum Observed Concentration (Tmax) of Salanersen in Serum
timeFrame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Ontario
country: Canada
facility: Children's Hospital of Eastern Ontario
city: Paris
country: France
facility: Hôpital Armand Trousseau
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Milano
country: Italy
facility: Fondazione Serena Onlus - Centro Clinico Nemo
city: Rome
country: Italy
facility: Pediatric Neurology Unit, Catholic University
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Leiden
country: Netherlands
facility: Centre For Human Drug Research
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki Dept of Neurology
city: Warsaw
country: Poland
facility: Instytut "Pomnik - Centrum Zdrowia Dziecka
city: Warszawa
country: Poland
facility: PRATIA S.A. MTZ Clinical Research Powered by Pratia
city: Bloomsbury
country: United Kingdom
facility: Great Ormond Street Hospital for Children
city: Sheffield
country: United Kingdom
facility: Sheffield Childrens Hospital
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: