BIIB115 for Spinal Muscular Atrophy

Not currently recruiting at 24 trial locations

Overseen By Global Biogen Clinical Trial Center

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Biogen

Must be taking: Onasemnogene abeparvovec

Must not be taking: Nusinersen, Risdiplam

Disqualifiers: Liver injury, Thrombotic microangiopathy, others

Compensation: Varies

Number of Visits: 23

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of BIIB115, a potential treatment for spinal muscular atrophy (SMA). Researchers seek to understand how people react to the drug and how the body processes it. The trial consists of two parts: the first involves healthy adult males receiving either the drug or a placebo (a substance with no active ingredients), while the second focuses on children with SMA who have received another treatment called onasemnogene abeparvovec. Children with SMA who have had this prior treatment might be suitable candidates for the trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, if you are in Part B and have been treated with nusinersen, you must wait at least 12 months from your last dose before starting BIIB115. Also, ongoing steroid treatment following onasemnogene abeparvovec is not allowed at the time of screening.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking certain medications like nusinersen, you must have stopped at least 12 months before the first dose of BIIB115. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that BIIB115 is likely to be safe for humans?

Research shows that BIIB115, also known as salanersen, is being tested for safety in both healthy volunteers and children with spinal muscular atrophy (SMA). Early results suggest that children with SMA who previously tried gene therapy experienced a noticeable slowdown in nerve damage when taking BIIB115. This is promising, but it's important to remember that these studies are still in the early stages, focusing mainly on safety and tolerability.

The current study aims to understand how the body processes BIIB115 and to identify any unwanted health problems. As an early-phase study, it specifically tests the safety of BIIB115. Researchers closely monitor participants for any side effects after treatment. While detailed safety information is not yet fully available, this ongoing research is crucial for understanding how well people tolerate BIIB115 and whether it is safe for wider use.

In summary, while the initial data is promising, the complete safety profile of BIIB115 is still being developed. Researchers carefully monitor participants to quickly identify and manage any potential side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about BIIB115 for Spinal Muscular Atrophy (SMA) because it offers a potential new way to address this condition. Unlike current treatments like Spinraza, Zolgensma, and Evrysdi, which have varying mechanisms and delivery methods, BIIB115 is delivered via an IT bolus injection and is being tested across multiple dosing regimens. This treatment's experimental design explores different dose levels and combinations, potentially offering insights into optimizing efficacy and safety. The possibility of a new dosing strategy or mechanism of action could make BIIB115 a game-changer in SMA therapy.

What evidence suggests that BIIB115 might be an effective treatment for spinal muscular atrophy?

Research has shown that BIIB115, also known as salanersen, may help treat spinal muscular atrophy (SMA). In earlier studies, children with SMA who had already received gene therapy experienced a significant slowing of nerve damage when given BIIB115. This trial will explore different dosages of BIIB115, with some participants receiving a single dose and others receiving multiple doses. Early evidence suggests that BIIB115 could effectively manage SMA symptoms and slow the disease's progression, offering a new option for patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Biogen

Are You a Good Fit for This Trial?

This trial is for healthy males aged 18-55 and children aged 0.5 to 12 with Spinal Muscular Atrophy (SMA) who've been treated with onasemnogene abeparvovec. Adults must have a BMI of 18-30 kg/m^2 and be in good health, while children need to weigh at least 7 kg and may benefit from treatment due to SMA.

Inclusion Criteria

Part A: Must be in good health as determined by the investigator, based on medical history and screening evaluations

Part A: Have a body mass index of 18 to 30 kg/m^2, inclusive

I weigh at least 7 kg.

Exclusion Criteria

I have a history of blood clotting disorders.

Part A: 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

Part A: 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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Part A)

Healthy volunteers receive a single dose of BIIB115 or placebo via IT bolus injection

1 day

1 clinic visit, 24-hour stay

Follow-up (Part A)

Participants are monitored for safety and effectiveness after treatment

13 months

Up to 6 clinic visits, 4 telephone calls

Treatment (Part B)

Pediatric SMA participants receive two doses of BIIB115 at two different times

2 days

2 clinic visits, 24-hour stay after each dose

Follow-up (Part B)

Participants are monitored for safety and effectiveness after treatment

25 months

Up to 14 clinic visits, 6 telephone calls

What Are the Treatments Tested in This Trial?

Interventions

• BIIB115

Trial Overview The study tests the safety and tolerability of BIIB115, given through spinal injection, comparing it with a placebo. It's conducted in two parts: one-time dosing for healthy adults (Part A), and multiple doses for pediatric SMA patients previously treated with gene therapy (Part B).

How Is the Trial Designed?

Group I: Part B: Long Term Extension (LTE): BIIB115 Dose 4 Experimental Treatment 1 Intervention

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.

Group II: Part B: Cohort 6: BIIB115 Dose 4 Experimental Treatment 1 Intervention

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

Group III: Part B: Cohort 5: BIIB115 Dose 3 Experimental Treatment 1 Intervention

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.

Group IV: Part A: Cohort 4: BIIB115 Dose 4 Experimental Treatment 1 Intervention

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

Group V: Part A: Cohort 3:BIIB115 Dose 3 Experimental Treatment 1 Intervention

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

Group VI: Part A: Cohort 2: BIIB115 Dose 2 Experimental Treatment 1 Intervention

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

Group VII: Part A: Cohort 1: BIIB115 Dose 1 Experimental Treatment 1 Intervention

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

Group VIII: Part A: Cohorts 1-4: BIIB115-Matching Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Biogen

Lead Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

Graduated from Queen's University, Kingston, Ontario, Canada

Published Research Related to This Trial

Nusinersen treatment in adults with spinal muscular atrophy (SMA) type 2 and 3 showed modest improvements in muscle strength over 26 months, with significant increases in strength observed at 6 and 14 months, but not thereafter.

The treatment was found to be safe, with the only reported side effect being post-lumbar puncture headache, and it stabilized motor function without significant changes in respiratory function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longer-term follow-up of nusinersen efficacy and safety in adult patients with spinal muscular atrophy types 2 and 3. Fainmesser, Y., Drory, VE., Ben-Shushan, S., et al.[2022]

Oral administration of sodium 4-phenylbutyrate (PB) significantly increases survival motor neuron (SMN) protein expression in leukocytes of patients with spinal muscular atrophy (SMA), suggesting a potential therapeutic benefit.

This study provides the first evidence of PB's effect in SMA patients and supports further investigation into its efficacy, backed by preliminary clinical data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phenylbutyrate increases SMN gene expression in spinal muscular atrophy patients. Brahe, C., Vitali, T., Tiziano, FD., et al.[2022]

A systematic review and meta-analysis of 42 studies involving 606 patients with spinal muscular atrophy (SMA) found that traditional biomarkers like lung function and serum levels do not effectively track disease progression over time.

However, potential biomarkers such as the SMA functional rating scale, compound muscle action potential (CMAP), and motor unit number estimation (MUNE) showed significant differences between SMA patients and controls, indicating they may be useful for further research into disease activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers of disease progression in adolescents and adults with 5q spinal muscular atrophy: a systematic review and meta-analysis. Gavriilaki, M., Moschou, M., Papaliagkas, V., et al.[2022]

Spinal muscular atrophy (SMA) is caused by a deletion of the SMN1 gene, leading to reduced SMN protein levels and resulting in muscle weakness and paralysis; early diagnosis and supportive care are crucial for improving patient outcomes.

Current treatments can help delay disease progression and improve quality of life, but they cannot reverse the damage already done to motor neurons or muscle cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal muscular atrophy: diagnosis, treatment and future prospects. Baioni, MT., Ambiel, CR.[2020]

In a phase 2 study involving 20 infants with infantile-onset spinal muscular atrophy, nusinersen treatment led to significant improvements in motor milestones, with 63% of participants showing incremental gains over 3 years.

The study also reported a favorable safety profile, with 75% of participants alive at the end of the study, although serious adverse events were common, primarily related to disease progression rather than the treatment itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of infantile-onset spinal muscular atrophy with nusinersen: final report of a phase 2, open-label, multicentre, dose-escalation study. Finkel, RS., Chiriboga, CA., Vajsar, J., et al.[2021]

Infantile-onset spinal muscular atrophy (SMA) is primarily caused by low levels of the Survival Motor Neuron (SMN) protein, which leads to the selective degeneration of spinal motor neurons, although the exact reasons for this selectivity are still unclear.

Recent advances in SMA research have led to the development of promising new therapies that focus on increasing SMN protein levels, marking significant progress in treatment options for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor neuron biology and disease: A current perspective on infantile-onset spinal muscular atrophy. Jha, NN., Kim, JK., Monani, UR.[2020]

Spinal muscular atrophy (SMA) is a severe childhood neurological disease caused by the degeneration of lower motor neurons, leading to significant muscle weakness.

There is a need for standardized and sensitive clinical outcome measures to effectively assess the impact of new treatments for SMA, as current assessments vary and their ability to detect changes is not well established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome measures in spinal muscular atrophy. Montes, J., Gordon, AM., Pandya, S., et al.[2009]

In a review of 15 studies involving 967 children, Nusinersen was found to have a low rate of definite adverse events (0.57%) and a higher rate of probable adverse events (7.76%), indicating it is generally safe for treating spinal muscular atrophy.

Nusinersen significantly reduced the incidence of serious and fatal adverse events compared to placebo, suggesting it not only has a favorable safety profile but also contributes to better overall health outcomes in children and adolescents with spinal muscular atrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in the treatment of spinal muscular atrophy in children and adolescents with nusinersen: A systematic review and meta-analysis. Zhong, ZJ., Zheng, PM., Dou, HH., et al.[2023]

In a 12-week trial involving 27 patients with spinal and bulbar muscular atrophy, the IGF-1 mimetic BVS857 was found to be generally safe, with no serious adverse events reported, although a high incidence of immunogenicity was observed in 72% of participants.

BVS857 treatment helped maintain thigh muscle volume (TMV) compared to a decrease in the placebo group, indicating potential efficacy in stabilizing muscle mass, but did not lead to improvements in muscle strength or function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and preliminary efficacy of an IGF-1 mimetic in patients with spinal and bulbar muscular atrophy: a randomised, placebo-controlled trial. Grunseich, C., Miller, R., Swan, T., et al.[2021]

Spinal muscular atrophy (SMA) is a genetic disorder caused by mutations in the SMN1 gene, affecting approximately 1 in 6000-10,000 newborns, with a carrier frequency of 1 in 40-60, highlighting the importance of genetic screening for early detection.

While there is currently no effective treatment for SMA, several promising strategies are being developed, including targeting the SMN2 gene, introducing functional SMN1, and exploring non-SMN targeting approaches, based on the disease's molecular mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal muscular atrophy: from gene discovery to clinical trials. Nurputra, DK., Lai, PS., Harahap, NI., et al.[2014]

This study identified mutations in the BICD2 gene as a cause of non-5q spinal muscular atrophy (SMA) in a Bulgarian family, highlighting the genetic diversity of SMA beyond the common SMN1 mutations.

The identified BICD2 mutations lead to altered protein interactions that disrupt dynein-mediated transport, which is crucial for motor neuron function, suggesting a potential mechanism for the disease's progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular defects in the motor adaptor BICD2 cause proximal spinal muscular atrophy with autosomal-dominant inheritance. Peeters, K., Litvinenko, I., Asselbergh, B., et al.[2021]

In a study of 95 non-ambulatory children with later-onset spinal muscular atrophy (SMA) treated with nusinersen, improvements in motor function were observed, particularly in those with no or mild scoliosis, as measured by the Hammersmith Functional Motor Score-Expanded (HFMSE) and the Revised Upper Limb Module (RULM).

A significant relationship was found between baseline scoliosis severity and motor function outcomes, with greater scoliosis (measured by Cobb angle) correlating with lower improvements in motor function, indicating that scoliosis severity may impact the efficacy of nusinersen treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nusinersen Treatment of Children with Later-Onset Spinal Muscular Atrophy and Scoliosis Is Associated with Improvements or Stabilization of Motor Function. Dunaway Young, S., Montes, J., Glanzman, AM., et al.[2023]

Induced pluripotent stem cells (iPSCs) derived from a family with chronic spinal muscular atrophy (SMA) were differentiated into motor neurons, revealing significant differences in neurite length and number among family members, which highlights the variability in disease manifestation.

The study found that levels of SMN protein and PLS3 decreased progressively during the differentiation of iPSC-derived motor neurons, suggesting that this decline may contribute to the increased vulnerability of motor neurons in SMA, although these levels have limited value as biomarkers for the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decay in survival motor neuron and plastin 3 levels during differentiation of iPSC-derived human motor neurons. Boza-Morán, MG., Martínez-Hernández, R., Bernal, S., et al.[2018]

New treatments for Spinal Muscular Atrophy (SMA), including gene therapy and splicing modulation, can significantly alter the disease's progression if started early, highlighting the importance of newborn screening for early detection.

Current evidence for these therapies is limited to a narrow range of patients, emphasizing the need for real-world data collection to better understand treatment effects across all SMA subtypes and improve clinical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Treatment of Spinal Muscular Atrophy - New Phenotypes, New Challenges, New Implications for Care. Schorling, DC., Pechmann, A., Kirschner, J.[2020]

Citations

1. ir.ionis.com ir.ionis.com/news-releases/news-release-details/ionis-announces-biogen-advance-salanersen-sma-registrational

Ionis announces Biogen to advance salanersen into SMA ... Interim Phase 1 data show children with SMA previously treated with gene therapy experienced a substantial slowing of neurodegeneration.

2. investors.biogen.com investors.biogen.com/news-releases/news-release-details/biogen-advance-investigational-spinal-muscular-atrophy-asset

Biogen to Advance Investigational Spinal Muscular Atrophy ... Salanersen (BIIB115/ION306) is a novel antisense oligonucleotide (ASO) with the potential to achieve high efficacy and once yearly dosing in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07221669

A Study to Learn About Salanersen's (BIIB115) Effects on ... In this study, researchers will learn more about the effects and safety of BIIB115, also known as salanersen.

4. curesma.org curesma.org/biogen-announces-advancement-of-investigational-sma-drug-salanersen-to-registrational-trials-based-on-positive-phase-1-results/

Biogen Announces Advancement of Investigational ... Biogen Inc. announced today that it will advance its investigational spinal muscular atrophy (SMA) treatment, salanersen (BIIB115/ION306), into registrational ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05575011

NCT05575011 | A Study to Learn About the Safety of ... In this study, researchers will learn about a study drug called BIIB115 in healthy adult male volunteers and in participants with spinal muscular atrophy ...

6. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-tolerability-of-biib115-for-children-with-spinal-muscular-atrophy-previously-treated-with-gene-therapy/

Study on the Safety and Tolerability of BIIB115 for Children ... This clinical trial tests the safety and tolerability of BIIB115, an injectable treatment for children with Spinal Muscular Atrophy who have ...