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Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA) (SMART)

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.
ClinicalTrials.gov Identifier: NCT04851873
Recruitment Status : Active, not recruiting
First Posted : April 21, 2021
Last Update Posted : May 17, 2023
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
To evaluate the safety, tolerability and efficacy of intravenous administration of OAV101 (AVXS-101) in patients with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene weighing ≥ 8.5 kg and ≤ 21 kg, over a 12 month period.

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

Detailed Description:

This is an open-label, single arm, multi-center study to evaluate the safety, tolerability and efficacy of IV OAV101 in SMA participants. The study will enroll participants that weigh ≥ 8.5 kg and ≤ 21 kg. An even weight distribution across the desired range will be achieved by aiming to enroll approximately 6-10 participants across 3 weight brackets (≥ 8.5-13 kg, > 13-17 kg, > 17-21 kg). Participants will receive a single administration of IV OAV101.

Participants who meet eligibility criteria at screening and baseline visits will receive a single-dose of IV OAV101 on Day 1 (Treatment period) and will be followed for a period of 12 months. The study will include a standard screening period that can last up to 45 days, during which eligibility will be assessed and baseline assessments will be performed prior to treatment.

For the study duration, participants will complete visits as defined in the Schedule of Assessments. Prednisolone treatment will be given per study protocol. On Day -1, participants will be admitted to the hospital for pre-treatment baseline procedures. On Day 1, participants will receive a 1-time IV infusion of OAV101 and will undergo in-patient safety monitoring over the next 48 hours, after which the participant may be discharged, based on Investigator judgment.

Safety monitoring will be performed as per study schedule and protocol requirement. Safety for the participants enrolled in the study will be evaluated by the study team together with Data Monitoring Committee (DMC) as described in the charter. An interim analysis for safety and efficacy maybe performed once the last participant completes 6-months of follow-up, and will include all available data up until that data cut-off. Final analysis will be planned after the 12 months visits (End of Study (EOS)).

After study completion eligible participants will be invited to enroll into Long Term follow-up study to collect additional safety and efficacy data.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Participants will receive a single administration of OAV101
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IIIb, Open-label, Single-arm, Single-dose, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of Gene Replacement Therapy With Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)
Actual Study Start Date : September 8, 2021
Estimated Primary Completion Date : July 5, 2023
Estimated Study Completion Date : July 5, 2023

Arm Intervention/treatment
Experimental: OAV101
Participants will receive a single IV dose administration of OAV101
Genetic: OAV101
Gene Therapy

Primary Outcome Measures :
  1. Number of participants with treatment emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 12 months ]
    An 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.

  2. Number of participants with important identified and important potential risks (Adverse Events of Special Interest (AESI)) [ Time Frame: 12 months ]

    The following are important identified and important potential risks (AESI) associated with OAV101: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Sensory abnormalities suggestive of ganglionopathy, and Thrombotic microangiopathy.

    These will be assessed by the investigator.

  3. Change from baseline in vital signs measurements - systolic and diastolic blood pressure [ Time Frame: 12 months ]
    Change from baseline in vital signs measurements - systolic and diastolic blood pressure (mmHg)

  4. Change from baseline in vital signs measurements - respiratory rate [ Time Frame: 12 months ]
    Change from baseline in vital signs measurements - respiratory rate (breaths per minute)

  5. Change from baseline in vital signs measurements - pulse [ Time Frame: 12 months ]
    Change from baseline in vital signs measurements - pulse (beats per minute)

  6. Change from baseline in vital signs measurements - temperature [ Time Frame: 12 months ]
    Change from baseline in vital signs measurements - temperature (degrees Celsius)

  7. Change from baseline in vital signs measurements - oxygen saturation level [ Time Frame: 12 months ]
    Change from baseline in vital signs measurements - oxygen saturation level (%)

Secondary Outcome Measures :
  1. Achievement of development motor milestones according to the modified and combined WHO-MGRS and Bayley scale of Infant and Toddler Development. [ Time Frame: 12 months ]
    The World Health Organization-Multicentre Growth Reference Study (WHO-MGRS) and Bayley scale of Infant and Toddler Development will be modified and combined into a single scale expressly for this study, to measure developmental motor milestones. These will be assessed via the milestone checklist, formed of 10 yes/no questions with optional video documentation. The developmental milestones are: head control, sitting with support, sitting without support, sitting without support for 30 seconds, hands-and-knees crawling, pulls to stand, standing with assistance, walking with assistance, standing alone and walking alone. A yes response indicates that the patient reached a particular development milestone.

  2. Change from baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE), as appropriate according to participant age [ Time Frame: 12 months ]
    The HFMSE was devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE is formed of 33 assessments rated from 0 (unable to perform functional task) to 2 (able to perform functional task unassisted). Higher scores indicated higher levels of motor ability.

  3. Change from baseline in Revised Upper Limb Module (RULM), as appropriate according to participant age. [ Time Frame: 12 months ]
    The RULM assesses motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. 'The scale consists of an entry item to establish functional levels and 19 items covering distal to proximal movements. The entry item is a modified version of the Brooke scale, including activities ranging from no functional use of hands (score 0) to full bilateral shoulder abduction (score 6). The entry item does not contribute to the total score but serves as a functional classification of overall upper limb functional ability. Of the remaining 19 items, 18 are scored on a 3 point scoring system and 1 item is scored on a 2 point scoring system. The test is performed unilaterally using the limb preferred by the participant. The total score ranges from 0, if all the items cannot be performed, to 37, if all the activities are achieved fully without any compensation. ' Higher scores indicate higher levels of motor ability.

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


  • Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic survival motor neuron 1 (SMN1) mutations (deletion or point mutations) and any copy of the survival motor neuron 2 (SMN2) gene.
  • Weight ≥ 8.5 kg and ≤ 21 kg at the time of Screening Visit 2
  • Naive to treatment or have discontinued an approved drug/therapy


  • Previous OAV101 use or previous use of any AAV9 gene therapy
  • Body Mass Index (BMI) < 3rd percentile based on World Health Organization (WHO) Child Growth Standard
  • Participant with history of aspiration pneumonia or signs of aspiration (eg, coughing or sputtering of food) within 4 weeks prior to screening
  • Anti-Adeno-associated virus serotype 9 (AAV9) antibody titer > 1:50 as determined by ligand binding immunoassay at the time of screening
  • History of gene therapy, hematopoietic transplantation, or solid organ transplantation

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 ClinicalTrials.gov identifier (NCT number): NCT04851873

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United States, Massachusetts
Novartis Investigative Site
Boston, Massachusetts, United States, 02115
United States, Missouri
Novartis Investigative Site
Saint Louis, Missouri, United States, 63110
Australia, New South Wales
Novartis Investigative Site
Randwick, New South Wales, Australia, 2031
Novartis Investigative Site
Leuven, Belgium, 3000
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H4A 3J1
Novartis Investigative Site
Garches, France, 92380
Novartis Investigative Site
Strasbourg Cedex, France, F 67098
Novartis Investigative Site
Roma, RM, Italy, 00168
Novartis Investigative Site
Lisboa, Portugal, 1600190
Novartis Investigative Site
Kaohsiung, Taiwan, 80756
Novartis Investigative Site
Taipei, Taiwan, 10002
United Kingdom
Novartis Investigative Site
London, United Kingdom, WC1N 3JH
Novartis Investigative Site
Newcastle Upon Tyne, United Kingdom, NE1 4LP
Sponsors and Collaborators
Novartis Pharmaceuticals
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Additional Information:
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04851873    
Other Study ID Numbers: COAV101A12306
First Posted: April 21, 2021    Key Record Dates
Last Update Posted: May 17, 2023
Last Verified: May 2023
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 https://www.clinicalstudydatarequest.com/.

URL: https://www.clinicalstudydatarequest.com/.

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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 ):
AVXS 101
gene therapy
Muscle atrophy
spinal and bulbar muscular atrophy
spinal muscular atrophy
bulbar muscular atrophy
muscle function
muscle wasting
atrophied muscle
loss of muscle strength
Additional relevant MeSH terms:
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Muscular Atrophy
Muscular Atrophy, Spinal
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases