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
- Conditions
- Healthy VolunteerMuscular Atrophy, Spinal
- Interventions
- Drug: Salanersen-Matching Placebo
- Registration Number
- NCT05575011
- Lead Sponsor
- Biogen
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 62
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
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: Cohort 1: Salanersen Dose 1 Salanersen Participants will receive a single dose of salanersen, Dose 1, via IT bolus injection, on Day 1. Part A: Cohort 2: Salanersen Dose 2 Salanersen Participants will receive a single dose of salanersen, Dose 2, via IT bolus injection, on Day 1. Part A: Cohort 3: Salanersen Dose 3 Salanersen Participants will receive a single dose of salanersen, Dose 3, via IT bolus injection, on Day 1. Part A: Cohort 4: Salanersen Dose 4 Salanersen Participants will receive a single dose of salanersen, Dose 4, via IT bolus injection, on Day 1. Part A: Cohorts 1-4: Salanersen-Matching Placebo Salanersen-Matching Placebo Participants will receive a single dose of salanersen-matching placebo, via IT bolus injection, on Day 1. Part B: Cohort 5: Salanersen Dose 3 Salanersen Pediatric SMA participants previously treated with onasemnogene abeparvovec will receive two doses of salanersen, Dose 3, via IT bolus injection at two separate time points. Part B: Cohort 6: Salanersen Dose 4 Salanersen Pediatric SMA participants previously treated with onasemnogene abeparvovec will receive two doses of salanersen, Dose 4, via IT bolus injectionat two separate time points.
- Primary Outcome Measures
Name Time Method Parts A and B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) Part A: Up to Day 393, Part B: Up to Day 720 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.
- Secondary Outcome Measures
Name Time Method Parts A and B: Concentration of Salanersen in Cerebral Spinal Fluid (CSF) Part A: Day 1 to Day 180, Part B: Days 1 and 360 Part A: Terminal Elimination Half-Life (t½) of Salanersen in CSF Day 1 to Day 180 Parts A and B: Concentration of Salanersen in Serum Part A: Day 1 to Day 180, Part B: Day 1 to 720 Parts A and B: Terminal Elimination Half-Life (t½) of Salanersen 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 Salanersen 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 Infinity (AUCinf) of Salanersen in Serum Part A: Day 1 to Day 180, Part B: Day 1 to Day 720 Parts A and B: Maximum Observed Concentration (Cmax) of Salanersen in Serum 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 Salanersen in Serum Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
Trial Locations
- Locations (17)
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Children's Hospital of Eastern Ontario
🇨🇦Ontario, Canada
Hôpital Armand Trousseau
🇫🇷Paris, France
Universitatsklinikum Essen
🇩🇪Essen, Germany
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Fondazione Serena Onlus - Centro Clinico Nemo
🇮🇹Milano, Italy
Pediatric Neurology Unit, Catholic University
🇮🇹Rome, Italy
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Centre For Human Drug Research
🇳🇱Leiden, Netherlands
UMC Utrecht
🇳🇱Utrecht, Netherlands
Instytut Centrum Zdrowia Matki Polki Dept of Neurology
🇵🇱Lodz, Poland
Instytut "Pomnik - Centrum Zdrowia Dziecka
🇵🇱Warsaw, Poland
PRATIA S.A. MTZ Clinical Research Powered by Pratia
🇵🇱Warszawa, Poland
Sheffield Childrens Hospital
🇬🇧Sheffield, United Kingdom
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Great Ormond Street Hospital for Children
🇬🇧Bloomsbury, United Kingdom