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Trial record 1 of 65 for:    STRENGTH | Spinal Muscular Atrophy
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Phase IIIb, Open-label, Multi-center Study to Evaluate Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally to Participants With SMA Who Discontinued Treatment With Nusinersen or Risdiplam (STRENGTH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT05386680
Recruitment Status : Active, not recruiting
First Posted : May 23, 2022
Last Update Posted : January 19, 2024
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This is an open-label, single arm, multi-center study. Approximately 28 participants aged 2 to <18 years will be enrolled stratified as 2 to 5 years and 6 to < 18 years. The study is comprised of 3 periods, Screening (up to 45 days), Treatment (1 day), and Follow-up (52 weeks).

Condition or disease Intervention/treatment Phase
Spinal Muscular Atrophy Genetic: OAV101 Phase 3

Detailed Description:

During the Screening period and on Day -1 (Baseline), eligibility will be assessed, including confirmation that nusinersen (Spinraza®) or risdiplam (Evrysdi®) have not been used for the defined period (4 month and 15 days prior to Day -1 respectively). On Day - 1 (Baseline) participants will be admitted to the hospital for pre-treatment baseline procedures. Prednisolone (or equivalent) will be given and continued as per the study protocol.

Participants who meet eligibility criteria at Screening and Baseline will receive a single dose of OAV101 (1.2 x 10^14 vector genomes) by lumbar intrathecal injection on Day 1 (Treatment) and will then undergo in-patient safety monitoring atleast the next 48 hours, after which the participant may be discharged according to Investigator judgement.

During Follow-up, safety monitoring will continue as per the visits defined in the Assessment Schedule. Safety for participants enrolled will be evaluated by the study team together with the Data Monitoring Committee (DMC).

Final analysis will be performed after all participants have completed Week 52 or discontinued prior to Week 52. At the end of study, participants will be invited to enroll in a Novartis-sponsored long-term follow-up study to monitor long-term safety and efficacy.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase IIIb, Open-label, Single-arm, Multi-center Study to Evaluate the Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally (1.2 x 10^14 Vector Genomes) to Participants 2 to < 18 Years of Age With Spinal Muscular Atrophy (SMA) Who Have Discontinued Treatment With Nusinersen (Spinraza®) or Risdiplam (Evrysdi®)
Actual Study Start Date : January 12, 2023
Estimated Primary Completion Date : December 3, 2024
Estimated Study Completion Date : December 3, 2024

Arm Intervention/treatment
Experimental: OAV-101
Intrathecal administration of OAV101 at a dose of 1.2 x 10^14 vector genomes, one time dose
Genetic: OAV101
Intrathecal administration of OAV101 at a dose of 1.2 x 10^14 vector genomes, one time dose
Other Names:
  • AVXS-101
  • Zolgensma

Primary Outcome Measures :
  1. Number and percentage of participants reporting AEs, related AEs, SAEs, and AESIs [ Time Frame: 52 weeks ]

    An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments.

    An AESI is primarily defined by using standard Medical Dictionary for Regulatory Activities (MedDRA) queries, and identified as follows: Hepatotoxicity, Thrombocytopenia, Thrombotic microangiopathy, Cardiac adverse events, and Dorsal root ganglia toxicity

Secondary Outcome Measures :
  1. Change from baseline to Week 52 visit in the HFMSE total score [ Time Frame: 52 weeks ]
    The Hammersmith Functional Motor Scale Expanded (HFMSE) is a SMA-specific 33-item assessment that is administered by clinical evaluators in a short period of time, requires minimal equipment, and is designed to factor in patient fatigue. Each motor skill item is scored on a 3-point Likert scale from 0 (no response) to 2 (full response), with a total score range of 0 to 66. A higher score indicates a higher ability level.

  2. Change from baseline to Week 52 visit in the RULM total Score [ Time Frame: 52 weeks ]
    The Revised Upper Limb Model (RULM) is a validated, SMA-specific assessment that measures motor performance in the upper limbs from childhood through adulthood in ambulatory and never ambulatory individuals with SMA. The revised version of the test consists of 19 scorable items: 18 items scored on a 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). These item scores are summed to give a total score ranging from 0 to 37 points with lower scores reflecting poorer ability.

  3. Change from baseline to Week 52 visit in Assessment of Caregiver Experience in ACEND instrument score [ Time Frame: 52 weeks ]
    The Assessment of Caregiver Experience in Neuromuscular Disease (ACEND) instrument quantifies the caregiver impact experienced by parents/caregivers of children affected with severe neuromuscular diseases, including children with SMA The total score is on a scale of 0 to 100 with a higher score indicating a greater impact on the caregiver.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   2 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

  • SMA diagnosis
  • Aged 2 to < 18 years
  • Have had at least four loading doses of nusinersen (Spinraza®) or at least 3 months of treatment with risdiplam (Evrysdi®) at Screening
  • Must have symptoms of SMA as defined in the protocol

Exclusion Criteria:

  • Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer using an immunoassay is reported as elevated
  • Clinically significant abnormalities in test results during screening
  • Contraindications for lumbar puncture procedure
  • At Baseline, participants are excluded if they received:

    • nusinersen (Spinraza®) or
    • risdiplam (Evrysdi®) within a defined timeframe
  • Vaccinations 2 weeks prior to administration of OAV101
  • Hospitalization for a pulmonary event, or for nutritional support within 2 months prior to Screening or inpatient major surgery planned.
  • Presence of an infection or febrile illness up to 30 days prior to administration of OAV101
  • Requiring invasive ventilation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05386680

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United States, Massachusetts
Novartis Investigative Site
Boston, Massachusetts, United States, 02215
United States, Virginia
Novartis Investigative Site
Norfolk, Virginia, United States, 23507
United States, Wisconsin
Novartis Investigative Site
Madison, Wisconsin, United States, 53792-7375
Australia, Victoria
Novartis Investigative Site
Parkville, Victoria, Australia, 3052
Novartis Investigative Site
Leuven, Belgium, 3000
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H4A 3J1
Novartis Investigative Site
Bron Cedex, France, 69677
Novartis Investigative Site
Toulouse Cedex, France, 31059
Novartis Investigative Site
Roma, RM, Italy, 00168
Novartis Investigative Site
Kurume city, Fukuoka, Japan, 830-0011
Novartis Investigative Site
Shinjuku ku, Tokyo, Japan, 162 8666
Novartis Investigative Site
Utrecht, Netherlands, 3584CX
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals Identifier: NCT05386680    
Other Study ID Numbers: COAV101B12302
First Posted: May 23, 2022    Key Record Dates
Last Update Posted: January 19, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Muscle atrophy
spinal and bulbar muscular atrophy
spinal muscular atrophy
bulbar muscular atrophy
muscle function
muscle wasting
atrophied muscle
loss of muscle strength
AVXS 101
gene therapy
Additional relevant MeSH terms:
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Muscular Atrophy
Muscular Atrophy, Spinal
Spinal Cord Diseases
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases