A Study to Learn About Salanersen's (BIIB115) Effects on Movement and Its Safety in Participants Aged 15 to 60 Years With Spinal Muscular Atrophy (SMA) Who Are Either New to SMA Treatment or Were Previously Treated With Risdiplam

Официальное название

An Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of Salanersen (BIIB115) in Participants Aged 15-60 Years With Spinal Muscular Atrophy Who Are Either Treatment-Naïve or Have Previously Been Treated With Risdiplam

Обзор

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 individuals with SMA who are between the ages of 15 and 60 years old. In most people living with SMA, changes to or a lack of a gene called survival motor neuron 1 (SMN1) - often referred to as gene mutations or variants - affect how this gene works. As a result, their bodies produce less SMN protein. Without enough of this protein, motor neurons and muscles cannot work properly. There is a similar gene called SMN2 that produces SMN protein, but it usually does not produce enough SMN protein on its own to make up for the changes in the SMN1 gene. Salanersen is a drug designed to help the SMN2 gene to make more working SMN protein. In this study, there will be 2 groups of participants: a group who has never received treatment for SMA before joining this study, and a group who has been treated with risdiplam, an approved drug for SMA . Those participants must not have received any other SMA treatments before and will need to stop their risdiplam treatment for the duration of the study. The main goal of this study is to learn more about how salanersen affects the participants' motor function. Researchers will use different tests and questionnaires to learn if motor function is changing over the study duration. The main question researchers want to answer in this study is: • For the group who has never been treated for SMA, how much do scores on the HFMSE movement test change at 12 months compared to the beginning of the study? The Hammersmith Functional Motor Scale - Expanded (HFMSE) has 33 activities that are scored which include sitting, lying down, walking, jumping, and more. Researchers will also learn more about: * The effects on participants' motor function and how well their nerves and muscles function. * The effects on participants' overall sense of change and how they perform daily activities. * 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. * How much salanersen gets into the fluid surrounding the brain and spinal cord. * How much salanersen gets into the blood. This study will be done as follows: * First, participants will be screened to check if they can join the study. The screening period may be up to 4 weeks. * This is an "open-label" study. This is a study in which the participants, study doctor, and site staff will know that participants are receiving salanersen. * All participants will receive salanersen through an intrathecal injection, or one that is given into the fluid surrounding the brain and spinal cord. * Participants will receive salanersen once every year for a total of 5 times throughout the study. * Including screening, participants will have 17 study visits and 9 telephone calls during this study, which will last up to 61 months in total.

Подробное описание

The primary objective of the SOLAR study is to evaluate the clinical efficacy of salanersen in participants with SMA who are treatment-naïve or previously treated with risdiplam. The secondary objective of the study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of salanersen.

Вмешательства

• Препарат Salanersen
  Administered Intrathecally

Первичные конечные точки

• Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Total Score in Treatment-Naïve Cohort [Срок оценки: At Month 12]

Вторичные конечные точки (12)

• Percentage of Participants With ≥ 3-Point Change From Baseline in HFMSE Total Score [Срок оценки: Up to Day 1825]
• Percentage of Participants With ≥ 2-Point Change From Baseline in Revised Upper Limb Module (RULM) Total Score [Срок оценки: Up to Day 1825]
• Percentage of Participants With ≥ 30-Meter Change From Baseline in 6-Minute Walk Test (6MWT) Distance (Ambulatory Participants Only) [Срок оценки: Up to Day 1825]
• Change From Baseline in HFMSE Total Score [Срок оценки: Up to Day 1825]
• Change From Baseline in RULM Total Score [Срок оценки: Up to Day 1825]
• Change From Baseline in Total 6MWT Distance (Ambulatory Participants Only) [Срок оценки: Up to Day 1825]
• Change From Baseline in Compound Muscle Action Potential (CMAP) Amplitudes [Срок оценки: Up to Day 1825]
• Patient Global Impression of Change (PGI-C) Score [Срок оценки: Up to Day 1825]
• Change From Baseline in SMA Independence Scale - Upper Limb Module (SMAIS-ULM) [Срок оценки: Up to Day 1825]
• Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Up to Day 1825]
• Concentration of Salanersen in Cerebrospinal Fluid (CSF) [Срок оценки: Up to Day 1460]
• Concentration of Salanersen in Serum [Срок оценки: Up to Day 1825]

Критерии участия

Критерии включения

• Participants aged 15 to 60 years, inclusive, at the time of informed consent
• Participants with genetic documentation of 5q Spinal Muscular Atrophy (SMA) (homozygous gene deletion or mutation or compound heterozygous mutation).
• Participants with clinical signs and symptoms consistent with SMA.
• Survival motor neuron 2 (SMN2) copy number ≥ 1.
• Participants with baseline Hammersmith Functional Motor Scale - Expanded (HFMSE) total score of ≥ 10 to ≤ 54.
• Participants who are able to sit without using support for at least 10 seconds.
• Participants with no prior treatment with myostatin inhibitors and a willingness to remain off concurrent myostatin inhibitor therapy for the duration of the study.
• Ambulatory and nonambulatory participants:

• Ambulatory participants must be able to walk at least 10 meters independently without assistance and are willing and able to complete the 6 Minute Walk Test (6MWT) at Screening.
• For participants in the treatment-naïve cohort:

• No prior treatment with an approved SMA Disease Modifying Therapy (DMT) or an investigational drug given for the treatment of SMA.
• For participants in the risdiplam-treated cohort:

• Currently receiving risdiplam treatment and have been on once-daily 5 milligrams (mg) risdiplam treatment for at least 6 months prior to Screening.
• Willing to stop risdiplam therapy for the duration of the study. The last dose of risdiplam must be taken the day before the first dose of salanersen.
• No prior treatment with nusinersen, onasemnogene abeparvovec-xioi/onasemnogene abeparvovec-brve (OA), other approved DMTs for SMA or investigational drugs given for the treatment of SMA apart from risdiplam.

Критерии исключения

• Respiratory insufficiency at Screening, defined by the medical necessity for invasive or noninvasive ventilation for > 6 hours during a 24-hour period (except for nocturnal bilevel positive airway pressure).
• Medical necessity for a gastric feeding tube, where the majority of nutrition is provided by this route, as assessed by the site Investigator at Screening.
• History of brain or spinal cord disease or other contraindications (e.g., severe scoliosis) that would interfere with the lumbar puncture (LP) procedures, Cerebrospinal fluid (CSF) circulation, efficacy assessments, or safety assessments (including a history of hydrocephalus or implanted shunt for CSF drainage), as assessed by the Investigator.
• Hospitalization for surgery, a pulmonary event, or nutritional support within 2 months prior to Screening or plans to undergo elective procedures or surgeries at any time after signing the Informed Consent Form (ICF) through the end of the study. Note: If prior scoliosis surgery has been performed, it must be done at least 1 year prior to Screening.
• Presence of an active medical issue (e.g., infection, recent fracture) that would make the participant unsuitable for inclusion, as assessed by the Investigator.
• Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 90 days or 5 half-lives of the treatment (if known), whichever is longer, prior to Screening. This includes neuromodulation therapy such as spinal cord stimulation.

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Childrens Hospital of the Kings Daughter Norfolk — Norfolk

Идентификаторы

NCT: NCT07444476 · 277SM303 · 2025-524054-34

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗