In short
Researchers are currently studying a medication called BIIB115 for potential use in treating spinal muscular atrophy (SMA), particularly in children who have previously received gene therapy. This clinical trial is designed to evaluate the safety, tolerability, and how the drug moves through the body in both healthy adult males and children with SMA. The study is divided into two parts: Part A involves healthy volunteers receiving a single dose of either BIIB115 or placebo, while Part B focuses on children with SMA who previously received onasemnogene abeparvovec (Zolgensma™) gene therapy. This research aims to provide important insights into how BIIB115 might benefit patients with SMA and establish appropriate dosing guidelines for potential future treatments.
Key points
- BIIB115 is being studied in a clinical trial for potential use in treating spinal muscular atrophy (SMA), particularly in children who previously received gene therapy with Zolgensma. The study includes both healthy adult males receiving a single dose and children with SMA receiving two doses, with the medication administered directly into the spinal canal. Researchers are primarily assessing the safety profile of BIIB115 by monitoring adverse events, while also studying how the drug moves through the body by measuring its concentration in cerebrospinal fluid and blood. The trial is designed to help determine appropriate dosing and evaluate potential benefits for patients with SMA who might need additional treatment options beyond gene therapy. This research represents an important step in developing new therapeutic approaches for SMA patients.
At a glance
- Study Drug
- BIIB115
- Study Population
- Healthy adult male volunteers (Part A) and children with SMA previously treated with onasemnogene abeparvovec (Part B)
- Administration Method
- Intrathecal (IT) bolus injection directly into the spinal canal
- Study Design: Part A
- Randomized, blinded, placebo-controlled with single ascending doses; 13-month duration with 6 clinic visits and 4 phone calls
- Study Design: Part B
- Open-label with multiple ascending doses; 25-month duration with 14 clinic visits and 6 phone calls
- Primary Outcome
- Number of participants with adverse events and serious adverse events
- Secondary Outcomes
- Concentration of BIIB115 in CSF and serum, half-life, area under the concentration-time curve, maximum concentration, and time to reach maximum concentration
- Post-dose Monitoring
- 24-hour observation in clinic after each dose
- Study Identifier
- NCT05575011
What is BIIB115?
BIIB115 is an investigational drug currently being studied for the treatment of Spinal Muscular Atrophy (SMA). This medication is particularly being evaluated in children with SMA who have previously been treated with another therapy called onasemnogene abeparvovec (also known by its brand name Zolgensma™). BIIB115 is administered as an injection directly into the spinal canal, which is called an intrathecal (IT) bolus injection. This delivery method allows the medication to reach the cerebrospinal fluid (CSF), which surrounds the brain and spinal cord.
What is Spinal Muscular Atrophy (SMA)?
Spinal Muscular Atrophy is a rare genetic disease that affects the motor neurons in the spinal cord and brainstem. These neurons are responsible for controlling muscle movement throughout the body. When these neurons don't function properly, muscles become weak and may waste away (atrophy). SMA can affect a person's ability to walk, eat, and even breathe. It is a serious condition that often appears in infancy or early childhood, though there are varying types with different levels of severity.
Current Clinical Study of BIIB115
BIIB115 is currently being investigated in a Phase 1 clinical trial. This trial aims to evaluate the safety, tolerability, and how the body processes the drug (pharmacokinetics) in both healthy adult males and children with SMA who have previously received onasemnogene abeparvovec treatment.
The main objectives of this study are:
- To assess the safety of BIIB115 by monitoring for adverse events (unwanted health problems that may or may not be caused by the study drug)
- To understand how the body processes BIIB115 by measuring drug levels in both the blood (serum) and cerebrospinal fluid (CSF)
- To determine appropriate dosing for future studies
Study Design and Structure
The clinical trial for BIIB115 is divided into two parts:
Part A: Single Dose in Healthy Adult Males
This part involves healthy adult male volunteers who will receive a single dose of either BIIB115 or a placebo. Important features of Part A include:
- Participants will be randomly assigned to one of four different dose groups (Dose 1, 2, 3, or 4) or a placebo group
- Neither the researchers nor the participants will know whether they're receiving BIIB115 or placebo (this is called "blinding" or "masking")
- Each participant will receive a single injection into the spinal canal (intrathecal injection)
- The treatment and follow-up period will last for 13 months
- Participants will have up to 6 clinic visits and 4 telephone calls during this period
Part B: Multiple Doses in Children with SMA
This part focuses specifically on children with SMA who have previously been treated with onasemnogene abeparvovec. Key aspects include:
- Children will be assigned to receive either Dose 3 or Dose 4 of BIIB115
- Each participant will receive two doses of BIIB115 at different time points
- Both researchers and participants will know they are receiving BIIB115 (this is called "open-label")
- 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 of the study, participants will remain under medical supervision for 24 hours after each dose to monitor for any immediate health issues or side effects.
Who Can Participate in the Study?
The study includes two distinct groups of participants:
- Healthy Adult Male Volunteers: These participants do not have SMA and will participate in Part A of the study.
- Pediatric SMA Patients: Children who have been diagnosed with Spinal Muscular Atrophy and have previously received treatment with onasemnogene abeparvovec (Zolgensma™). These participants will take part in Part B of the study.
How is BIIB115 Administered?
BIIB115 is given as an intrathecal (IT) bolus injection. This means the medication is injected directly into the spinal canal, where it can enter the cerebrospinal fluid surrounding the brain and spinal cord.
For healthy volunteers in Part A, this is a one-time injection. For children with SMA in Part B, they will receive two separate injections at different time points during the study.
What Outcomes Are Being Measured?
The study is collecting several types of data to evaluate BIIB115:
Primary Outcome:
- Safety assessment: The number of participants who experience adverse events (AEs) or serious adverse events (SAEs). An adverse event is any unwanted medical occurrence during the study, while a serious adverse event is one that results in death, is life-threatening, requires hospitalization, causes disability, or is otherwise medically significant.
Secondary Outcomes:
- How BIIB115 moves through the body, including:
- Concentration levels of BIIB115 in the cerebrospinal fluid and blood
- How long BIIB115 stays in the body (terminal elimination half-life)
- The total amount of drug exposure over time (area under the curve or AUC)
- The highest concentration reached (maximum observed concentration or Cmax)
- How long it takes to reach the highest concentration (time to maximum concentration or Tmax)
Safety Monitoring During the Study
Throughout the study, participants will be closely monitored for any side effects or adverse events. Safety is the primary concern, which is why:
- Participants stay in the clinic for 24 hours after receiving each dose
- Multiple follow-up visits and phone calls are scheduled throughout the study period
- Any adverse events are thoroughly documented and evaluated
- Blood and cerebrospinal fluid samples are collected to monitor drug levels and body responses
The extensive follow-up periods (13 months for Part A and 25 months for Part B) allow researchers to identify both short-term and long-term effects of BIIB115 treatment.