Une étude pour en apprendre davantage sur les effets du salanersen (BIIB115) sur le mouvement et sa sécurité chez des participants âgés de 15 à 60 ans atteints d'amyotrophie spinale (SMA) qui sont soit nouveaux au traitement de la SMA, soit ont été précédemment traités par le risdiplam (SOLAR)
Étude en ouvert de phase 3 évaluant l'efficacité et la tolérance du salanersen (BIIB115) chez des participants âgés de 15 à 60 ans atteints d'amyotrophie spinale, naïfs de traitement ou ayant été préalablement traités par le risdiplam
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.
Aperçu de l'étude
Statut
Statut
Les conditions
Les conditions
Intervention / Traitement
Intervention / Traitement
Description détaillée
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.
Type d'étude
Type d'étude
Inscription (Estimé)
Inscription
Phase
Phase
- Phase 3
Contacts et emplacements
Coordonnées de l'étude
Coordonnées de l'étude
- Nom: US Biogen Clinical Trial Center
- Numéro de téléphone: 866-633-4636
- E-mail: clinicaltrials@biogen.com
Sauvegarde des contacts de l'étude
- Nom: Global Biogen Clinical Trial Center
- E-mail: clinicaltrials@biogen.com
Lieux d'étude
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Beijing, Chine, 100730
- Recrutement
- Peking Union Medical College Hospital
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California
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Palo Alto, California, États-Unis, 94304
- Recrutement
- Stanford University Medical Center
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Contact:
- Numéro de téléphone: 650-725-7622
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Chercheur principal:
- John Day
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Virginia
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Norfolk, Virginia, États-Unis, 23507
- Recrutement
- Childrens Hospital of the Kings Daughter Norfolk
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Chercheur principal:
- Crystal Proud
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Contact:
- Numéro de téléphone: 757-668-6981
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Critères de participation
Critère d'éligibilité
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Key Inclusion Criteria:
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Participants aged 15 to 60 years, inclusive, at the time of informed consent
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Participants with genetic documentation of 5q Spinal Muscular Atrophy (SMA) (homozygous gene deletion or mutation or compound heterozygous mutation).
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Participants with clinical signs and symptoms consistent with SMA.
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Survival motor neuron 2 (SMN2) copy number ≥ 1.
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Participants with baseline Hammersmith Functional Motor Scale - Expanded (HFMSE) total score of ≥ 10 to ≤ 54.
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Participants who are able to sit without using support for at least 10 seconds.
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Participants with no prior treatment with myostatin inhibitors and a willingness to remain off concurrent myostatin inhibitor therapy for the duration of the study.
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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.
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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.
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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.
Key Exclusion Criteria:
- 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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Nombre de bras
Armes et Interventions
Groupe de participants / BrasGroupe de participants / Bras |
Intervention / TraitementIntervention / Traitement |
|---|---|
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Expérimental: Treatment-Naïve Cohort
Treatment-naïve participants will receive salanersen 80 milligrams (mg) by intrathecal (IT) lumbar puncture (LP) every 12 months for a total of five doses. |
Administered Intrathecally
Autres noms:
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Expérimental: Risdiplam-Treated Cohort
Risdiplam-treated participants will receive salanersen 80 mg by IT LP every 12 months for a total of five doses. |
Administered Intrathecally
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Total Score in Treatment-Naïve Cohort
Délai: At Month 12
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The HFMSE is a tool used to assess motor function in individuals with SMA. Participants will be asked to complete a specific movement and are then graded on the quality and execution of that movement. Higher scores indicate higher levels of motor ability. The overall score is the sum of the scores for all 33 items, with a maximum score of 66 with higher scores depicting better ability to perform activities. |
At Month 12
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Mesures de résultats secondaires
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Nombre de participants avec des événements indésirables (EI) et des événements indésirables graves (EIG)
Délai: Jusqu'au jour 1825
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Jusqu'au jour 1825
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Concentration de Salanersen dans le liquide céphalo-rachidien (LCR)
Délai: Jusqu'au jour 1460
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Jusqu'au jour 1460
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Concentration de Salanersen dans le sérum
Délai: Jusqu'au jour 1825
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Jusqu'au jour 1825
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Percentage of Participants With ≥ 3-Point Change From Baseline in HFMSE Total Score
Délai: Up to Day 1825
|
The HFMSE is a tool used to assess motor function in individuals with SMA. Participants will be asked to complete a specific movement and are then graded on the quality and execution of that movement. Higher scores indicate higher levels of motor ability. The overall score is the sum of the scores for all 33 items, with a maximum score of 66 with higher scores depicting better ability to perform activities. |
Up to Day 1825
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Percentage of Participants With ≥ 2-Point Change From Baseline in Revised Upper Limb Module (RULM) Total Score
Délai: Up to Day 1825
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The RULM is developed to assess upper limb functional abilities of participants with SMA. This test consists of a total of 20 upper limb performance items that are reflective of activities of daily living. The RULM is scored from 0 to 37 points, with higher scores indicating better function. |
Up to Day 1825
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Percentage of Participants With ≥ 30-Meter Change From Baseline in 6-Minute Walk Test (6MWT) Distance (Ambulatory Participants Only)
Délai: Up to Day 1825
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The 6MWT is a submaximal exercise test used to assess an individual's functional exercise capacity. It measures the distance covered in 6 minutes on a flat, hard surface, providing valuable information about aerobic capacity and endurance. |
Up to Day 1825
|
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Change From Baseline in HFMSE Total Score
Délai: Up to Day 1825
|
The HFMSE is a tool used to assess motor function in individuals with SMA. Participants will be asked to complete a specific movement and are then graded on the quality and execution of that movement. Higher scores indicate higher levels of motor ability. The overall score is the sum of the scores for all 33 items, with a maximum score of 66 with higher scores depicting better ability to perform activities. |
Up to Day 1825
|
|
Change From Baseline in RULM Total Score
Délai: Up to Day 1825
|
The RULM is developed to assess upper limb functional abilities of participants with SMA. This test consists of a total of 20 upper limb performance items that are reflective of activities of daily living. The RULM is scored from 0 to 37 points, with higher scores indicating better function. |
Up to Day 1825
|
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Change From Baseline in Total 6MWT Distance (Ambulatory Participants Only)
Délai: Up to Day 1825
|
The 6MWT is a submaximal exercise test used to assess an individual's functional exercise capacity. It measures the distance covered in 6 minutes on a flat, hard surface, providing valuable information about aerobic capacity and endurance. |
Up to Day 1825
|
|
Change From Baseline in Compound Muscle Action Potential (CMAP) Amplitudes
Délai: Up to Day 1825
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CMAP is a well validated method for tracking disease progression in neuromuscular disorders such as SMA and amyotrophic lateral sclerosis and has been proposed as a potential biomarker of a therapeutic effect in SMA. CMAPs will be performed for the following nerve-muscle pairs: ulnar-abductor digiti minimi and peroneal-tibialis anterior. |
Up to Day 1825
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Patient Global Impression of Change (PGI-C) Score
Délai: Up to Day 1825
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PGI-C is a self-reported 7-point scale evaluating the participant's perception of change in disease state since baseline. The scale ranges from 1 to 7, where 1= very much improved; 2= much improved; 3= minimally improved; 4= no change; 5= minimally worse; 6= much worse; or 7= very much worse. Lower scores indicate clinical improvement, and higher scores indicate disease worsening. |
Up to Day 1825
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Change From Baseline in SMA Independence Scale - Upper Limb Module (SMAIS-ULM)
Délai: Up to Day 1825
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The SMAIS-ULM is a validated tool designed to assess the level of independence in daily activities related to upper limb functionality for individuals with Type II and nonambulant Type III SMA. The 22 items assess upper limb focused tasks across 5 domains of typical daily activities (bathing/hygiene, dressing, eating/drinking, picking up/moving objects, and other tasks) scored on a 3-point scale (0 = I cannot do this at all without help; 1 = I need some help; and 2 = I do not need help). Higher scores indicate greater independence. |
Up to Day 1825
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Collaborateurs et enquêteurs
Parrainer
Parrainer
Les enquêteurs
Les enquêteurs
- Directeur d'études: Medical Director, Biogen
Publications et liens utiles
Liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Début de l'étude
Achèvement primaire (Estimé)
Achèvement primaire
Achèvement de l'étude (Estimé)
Achèvement de l'étude
Dates d'inscription aux études
Première soumission
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Première publication
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour publiée
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
Autres numéros d'identification d'étude
- 277SM303
- 2025-524054-34 (Autre identifiant: EU Trial (CTIS) Number)
- 2025 (Subvention/contrat des NIH des États-Unis)
Plan pour les données individuelles des participants (IPD)
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Description du régime IPD
In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
Informations sur les médicaments et les dispositifs, documents d'étude
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