A Study to Learn About Salanersen's (BIIB115) Effects on Movement and Its Safety When Given Before Symptoms Appear in Babies With Genetically Diagnosed Spinal Muscular Atrophy (SMA)

Official title

An Open-Label Study to Assess the Efficacy and Safety of Multiple Doses of Salanersen (BIIB115) Delivered Intrathecally to Treatment-Naïve, Presymptomatic Infants With Genetically Diagnosed Spinal Muscular Atrophy

Overview

In this study, researchers will learn more about the effects and safety of BIIB115, also known as salanersen. Specifically, researchers will learn more about how salanersen works in babies who have been diagnosed with SMA through genetic testing but have not yet started showing signs or symptoms. Most people with SMA have changes in a gene called survival motor neuron 1, also known as SMN1. These changes lower the amount of SMN protein in their bodies. Without enough of this protein, motor neurons and muscles cannot work properly. A similar gene called SMN2 can help replace some of the lost SMN protein in the body. Salanersen works by helping the SMN2 gene to make more SMN protein. In this study, participants will have either 2 SMN2 copies or 3 SMN2 copies. The higher the copy number, the less severe the participant's SMA is. The main goal of this study is to see if starting salanersen before signs or symptoms appear can prevent signs or symptoms of SMA or make them less severe. Researchers will use different tests to learn if motor symptoms are changing, including the World Health Organization (WHO) motor milestones. The main questions researchers want to answer in this study are: * How many participants with 2 copies of the SMN2 gene can sit without support at 12 months? * How many participants with 3 copies of the SMN2 gene can walk alone at 18 months? Researchers will also learn more about: * The effects on participants' motor symptoms and how many new movement milestones participants achieve. * How many participants stay free of SMA symptoms * How much salanersen gets into the fluid surrounding the brain and spinal cord. * How much salanersen gets into the blood. * How many participants have adverse events or serious adverse events. Adverse events are health problems that may or may not be caused by the study drug. This study will be done as follows: * First, participants will be screened to check if they can join the study. The screening period will be up to 28 days. * This is an "open label" study. This is a study in which the participants, study doctor, and site staff know which study drug participants are receiving. In this study, all participants will receive salanersen through an intrathecal injection, or one that is given into the fluid surrounding the brain and spinal cord. * There will be 2 parts in this study. During Part 1, participants will receive 2 doses of salanersen, about 12 months apart from each other. Part 1 will last up to 25 months. * During Part 2, participants will continue to receive salanersen. They will receive up to 3 doses, 12 months apart from each other. Part 2 will last up to 36 months. * During Part 1, participants will have up to 11 clinic visits and up to 3 phone calls. During Part 2, participants will have up to 7 clinic visits and up to 12 phone calls.

Detailed description

For Part 1 of the study, the primary objective is to evaluate the clinical efficacy of salanersen in participants with genetically diagnosed SMA, and the secondary objective is to evaluate safety and tolerability, pharmacokinetics (PK), and effect on biomarkers after treatment with salanersen in participants with genetically diagnosed SMA.

For Part 2 of the study, the primary objective is to evaluate the long-term clinical efficacy of salanersen in participants with genetically diagnosed SMA, and the secondary objective is to evaluate the long-term safety and tolerability, PK, and effect on biomarkers after treatment with salanersen in participants with genetically diagnosed SMA.

Interventions

• Drug Salanersen
  Administered intrathecally

Primary outcome measures

• Part 1: Percentage of Participants with 2 Survival Motor Neuron 2 (SMN2) Copies Sitting Without Support (for at Least 10 Seconds) [Time frame: At Month 12]
• Part 1: Percentage of Participants with 3 SMN2 Copies Walking Alone (for at Least 5 Steps) [Time frame: At Month 18]
• Part 2: Percentage of Participants Attaining and Maintaining World Health Organization (WHO) Motor Milestones [Time frame: Up to Day 1825]

Secondary outcome measures (12)

• Part 1: Percentage of Participants Attaining World Health Organization (WHO) Motor Milestones [Time frame: Up to Day 730]
• Parts 1 and 2: Percentage of Participants Attaining Hammersmith Infant Neurological Examination Section 2 (HINE-2) Motor Milestones [Time frame: Up to Day 1825]
• Parts 1 and 2: Change From Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale [Time frame: Up to Day 1825]
• Parts 1 and 2: Change From Baseline in Compound Muscle Action Potential (CMAP) Amplitudes [Time frame: Up to Day 1825]
• Part 1: Percentage of Participants who Remain Free of Clinically Manifested Spinal Muscular Atrophy (SMA) [Time frame: Up to Day 730]
• Part 2: Hammersmith Functional Motor Scale Expanded (HFMSE) Total Score [Time frame: Up to Day 1825]
• Part 2: Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) [Time frame: Up to Day 1825]
• Part 2: Revised Upper Limb Module (RULM) Total Score [Time frame: Up to Day 1825]
• Part 2: Change From Baseline in Revised Upper Limb Module (RULM) [Time frame: Up to Day 1825]
• Part 2: Percentage of Participants who Develop Spinal Muscular Atrophy (SMA) Subtypes (Type 1, 2,3a and 3b) As Assessed by the Investigator [Time frame: Up to Day 1825]
• Parts 1 and 2: Time to Death (Overall Survival) [Time frame: Up to Day 1825]
• Parts 1 and 2: Time to Death or Permanent Ventilation [Time frame: Up to Day 1825]

Eligibility criteria

Inclusion criteria

-≤42 days of age at first dose of salanersen.

• Genetic documentation of 5q SMA homozygous gene deletion or mutation or compound heterozygous mutation.
• Two or three copies of the survival motor neuron 2 (SMN2) gene.
• Ulnar compound muscle action potential (CMAP) amplitude ≥2 millivolt (mV) at Screening and Day 1 predose.
• Body weight ≥3rd percentile for age based on World Health Organization (WHO) Child Growth Standards at the time of informed consent.

Exclusion criteria

• Any clinical signs or symptoms at Screening or Day 1 predose that are, in the opinion of the Investigator, strongly suggestive of SMA.
• Areflexia on neurologic examination at biceps, knee, or ankle at Screening or Day 1 Predose.
• Hypoxemia (oxygen saturation <96% awake or asleep without any supplemental oxygen or respiratory support, or for altitudes >1000 meters (m), oxygen saturation of <92% awake or asleep without any supplemental oxygen or respiratory support).
• Diagnosis of neonatal respiratory distress syndrome necessitating surfactant replacement therapy or invasive ventilatory support.
• Any reason, anatomical or otherwise (including hematology/coagulation laboratory results), that presents increased risk of complication from the LP procedures or safety assessments.
• Any prior treatment with an approved SMA disease-modifying therapy (e.g., nusinersen, onasemnogene abeparvovec-xioi \[OA\], and/or risdiplam), a myostatin inhibitor therapy, or an investigational drug given for the treatment of SMA.

Note: Other protocol-defined inclusion/exclusion criteria will apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• Ann and Robert H Lurie Childrens Hospital of Chicago — Chicago
• Neurology Rare Disease Center — Flower Mound
• Childrens Hospital of the Kings Daughter Norfolk — Norfolk

China · 2 centers

• Guangzhou Woman and Children's Medical Center_Guangzhou — Guangzhou
• Childrens Hospital of Fudan University_Shanghai — Shanghai

Brazil · 1 center

• Hospital da Crianca de Brasilia — Distrito Federal

Japan · 1 center

• Japan Institute for Health Security National Center for Global Health and Medicine — Tokyo

Identifiers

NCT: NCT07221669 · 277SM302 · 2025-523116-37

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗