Et studie til at undersøge Salanersen's (BIIB115) virkning på bevægelse og dets sikkerhed hos deltagere i alderen 15 til 60 år med spinal muskelatrofi (SMA), som enten er nye til SMA-behandling eller tidligere er behandlet med risdiplam (SOLAR)
Et åbent, fase 3-studie til evaluering af effekt og sikkerhed af salanersen (BIIB115) hos deltagere i alderen 15-60 år med spinal muskelatrofi, der enten er behandlingsnaive eller tidligere har fået behandling med 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.
Studieoversigt
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 3
Kontakter og lokationer
Studiekontakt
- Navn: US Biogen Clinical Trial Center
- Telefonnummer: 866-633-4636
- E-mail: clinicaltrials@biogen.com
Undersøgelse Kontakt Backup
- Navn: Global Biogen Clinical Trial Center
- E-mail: clinicaltrials@biogen.com
Studiesteder
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California
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Palo Alto, California, Forenede Stater, 94304
- Rekruttering
- Stanford University Medical Center
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Kontakt:
- Telefonnummer: 650-725-7622
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Ledende efterforsker:
- John Day
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Virginia
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Norfolk, Virginia, Forenede Stater, 23507
- Rekruttering
- Childrens Hospital of the Kings Daughter Norfolk
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Ledende efterforsker:
- Crystal Proud
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Kontakt:
- Telefonnummer: 757-668-6981
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Beijing, Kina, 100730
- Rekruttering
- Peking Union Medical College Hospital
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: 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
Andre navne:
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Eksperimentel: 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
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Total Score in Treatment-Naïve Cohort
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Antal deltagere med bivirkninger (AEs) og alvorlige bivirkninger (SAEs)
Tidsramme: Op til dag 1825
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Op til dag 1825
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Koncentrationen af Salanersen i Cerebrospinalvæske (CSF)
Tidsramme: Op til dag 1460
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Op til dag 1460
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Koncentration af Salanersen i serum
Tidsramme: Op til dag 1825
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Op til dag 1825
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Percentage of Participants With ≥ 3-Point Change From Baseline in HFMSE Total Score
Tidsramme: Up to Day 1825
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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. |
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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: Up to Day 1825
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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. |
Up to Day 1825
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Change From Baseline in RULM Total Score
Tidsramme: 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)
Tidsramme: 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 Compound Muscle Action Potential (CMAP) Amplitudes
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Studieleder: Medical Director, Biogen
Publikationer og nyttige links
Hjælpsomme links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 277SM303
- 2025-524054-34 (Anden identifikator: EU Trial (CTIS) Number)
- 2025 (U.S. NIH-bevilling/kontrakt)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
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