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Spinal Muscular AtrophyPhase 3SMARTNCT04851873

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

A Phase 3 study testing OAV101 in people with Spinal Muscular Atrophy, run by Novartis Pharmaceuticals at 13 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 17 years
Conditions the study is for
Spinal Muscular Atrophy
What is being tested?
OAV101
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
13 sitesin 9 countries
Study dates
8 Sep 2021to 13 Jun 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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

Who cannot join

  • Previous OAV101 use or previous use of any adeno-associated virus serotype 9 (AAV9) gene therapy
  • BMI < 3rd percentile
  • Participant with history of aspiration pneumonia or signs of aspiration
  • Elevated anti-AAV9 antibody
  • History of gene therapy, hematopoietic transplantation, or solid organ transplantation
  • Inability to take corticosteroids
Show all 13Show fewer
  • Concomitant use of immunosuppressive therapy
  • Requiring invasive ventilation, tracheostomy or awake non-invasive ventilation 9. Administration of vaccines 2 weeks prior to infusion of OAV101
  • Awake hypoxemia or awake oxygen saturation level decrease
  • Hepatic dysfunction
  • Presence of a confirmed or suspected infection
  • If previously treated with disease modifying therapy, specified washout times apply
  • Documented any parental consanguinity.

Trial locations and contacts

13 sites in 9 countries.

13 sites in 9 countries

United States2 sites
  • Novartis Investigative Site

    Boston, Massachusetts, 02115

  • Novartis Investigative Site

    St Louis, Missouri, 63110

Other trials in United States

France2 sites
  • Novartis Investigative Site

    Garches, 92380

  • Novartis Investigative Site

    Strasbourg, 67000

Other trials in France

Taiwan2 sites
  • Novartis Investigative Site

    Kaohsiung City, 80756

  • Novartis Investigative Site

    Taipei, 10002

Other trials in Taiwan

United Kingdom2 sites
  • Novartis Investigative Site

    London, WC1N 3JH

  • Novartis Investigative Site

    Newcastle upon Tyne, NE1 4LP

Other trials in United Kingdom

Australia1 site
  • Novartis Investigative Site

    Randwick, New South Wales, 2031

Other trials in Australia

Belgium1 site
  • Novartis Investigative Site

    Leuven, 3000

Other trials in Belgium

Canada1 site
  • Novartis Investigative Site

    Montreal, Quebec, H4A 3J1

Other trials in Canada

Italy1 site
  • Novartis Investigative Site

    Roma, RM, 00168

Other trials in Italy

Portugal1 site
  • Novartis Investigative Site

    Lisbon, 1600190

Other trials in Portugal

About this study

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)

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.

Read the detailed description

This was an open-label, single arm, multi-center study designed to evaluate the safety, tolerability and efficacy of OAV101 in participants with SMA who weigh ≥ 8.5 kg and ≤ 21 kg. The study aimed to enroll approximately 24 to 30 participants, with approximately 6 to 10 participants across each of 3 weight brackets (8.5 to 13 kg, >13 to 17 kg, >17 to 21 kg).

Eligible participants received a single administration of OAV101 at the approved dose of 1.1e14 vg/kg on Day 1 (Treatment period), and were followed for a period of 12 months.

Participants were admitted to the hospital on Day -1 for pre-treatment baseline procedures. After receiving OAV101 on Day 1, participants underwent in-patient safety monitoring over the next 48 hours, after which the participant could be discharged, based on Investigator judgment.

After study completion, eligible participants could enroll into a Long Term follow-up study to collect additional safety and efficacy data. (COAV101A12308 (NCT05335876) https://classic.clinicaltrials.gov/ct2/show/NCT05335876?term=COAV101A12308\&draw=2\&rank=1))

Being tested
OAV101
Keywords
Zolgensma, OAV101, AVXS 101, gene therapy, Muscle atrophy, SBMA, spinal and bulbar muscular atrophy, spinal muscular atrophy, bulbar muscular atrophy, muscle function, myopathy, muscle wasting, atrophied muscle, loss of muscle strength
Medical subject headings
Muscular Atrophy, Spinal, Muscular Atrophy, Bulbo-Spinal Atrophy, X-Linked, Muscular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OAV101Genetic

    Gene Therapy - 1.1e14 vector genome (vg)/kg as a one-time IV infusion was administered over approximately 60 minutes.

Study groups in NCT04851873
Study groupRoleWhat they receive
OAV101ExperimentalParticipants received a single IV dose administration of OAV101
Receives: Genetic: OAV101

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Weight Bracket

    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.

    Measured: Up to Month 12

  2. Number of Participants With Important Identified and Important Potential Risks (Adverse Events of Special Interest (AESI)) by Risk Name and Weight Bracket

    Important identified and important potential risks included the following AESIs: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Dorsal root ganglia toxicity and Thrombotic microangiopathy.

    These were assessed by the investigator.

    Measured: Up to Month 12

  3. Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Systolic and Diastolic Blood Pressure

    Change from baseline in vital signs measurements - systolic and diastolic blood pressure (mmHg).

    Systolic Blood Pressure-Low:<=5th percentile of the age(Any Age), High:>=90th percentile of the age, gender, and height group (<18 yrs).

    Diastolic Blood Pressure-High:>=90th percentile of the age, gender, and height group(<18 yrs).

    Measured: 12 months

  4. Change From Baseline in Vital Signs Measurements - Systolic Blood Pressure (mmHg)

    Measured: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52

  5. Change From Baseline in Vital Signs Measurements - Diastolic Blood Pressure (mmHg)

    Measured: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52

  6. Change From Baseline in Vital Signs Measurements - Respiratory Rate (Breaths/Min)

    Change from baseline in vital signs measurements - Respiratory Rate (breaths/min)

    Measured: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52

  7. Change From Baseline in Vital Signs Measurements - Pulse Rate (Beats/Min)

    Change from baseline in vital signs measurements - Pulse Rate (beats/min

    Measured: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52

  8. Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Temperature

    Change from baseline in vital signs measurements - temperature (degrees Celsius)

    Temperature-Low:<=35ºC(Any Age),High:>=38.4ºC(<18 yrs).

    Measured: 12 months

  9. Change From Baseline in Vital Signs Measurements - Temperature (Degrees Celsius)

    Measured: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52

  10. Change From Baseline in Vital Signs Measurements - Oxygen Saturation Level

    Change from baseline in vital signs measurements - oxygen saturation level (%).

    Oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated+saturated) in the blood and then multiplied by 100.

    Measured: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52

Secondary outcomes (3)
  1. Achievement of Development Motor Milestones According to the Modified and Combined WHO-MGRS and Bayley Scale of Infant and Toddler Development.

    The World Health Organization-Multicentre Growth Reference Study (WHO-MGRS) and Bayley scale of Infant and Toddler Development was modified and combined into a single scale expressly for this study, to measure developmental motor milestones. These were 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.

    Measured: Baseline, Week 26 and Week 52

  2. Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE), as Appropriate According to Participant Age

    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. 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 level of ability.

    Measured: Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52

  3. Change From Baseline in Revised Upper Limb Module (RULM), as Appropriate According to Participant Age.

    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.

    Measured: Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Apr 2021
  2. Study start8 Sep 2021
  3. Primary completion13 Jun 2023
  4. Study completion13 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Participants will receive a single administration of OAV101
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04851873
Sponsor's protocol ID
COAV101A12306
Other IDs
2020-005995-37
Acronym
SMART
Status last verified
Oct 2024
First submitted
6 Apr 2021
Last updated
9 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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/.

Publications

  • McMillan HJ, Baranello G, Farrar MA, Zaidman CM, Moreno T, De Waele L, Jong YJ, Laugel V, Quijano-Roy S, Mercuri E, Chien YH, Straub V, Darras BT, Seibert J, Bernardo Escudero R, Alecu I, Freischlager F, Muntoni F; SMART Study Group. Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b SMART Study. Neurology. 2025 Jan 28;104(2):e210268. doi: 10.1212/WNL.0000000000210268. Epub 2024 Dec 30.

    PubMed 39804575

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing OAV101 in people with Spinal Muscular Atrophy, run by Novartis Pharmaceuticals at 13 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States, France, Taiwan, United Kingdom, Australia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Weight Bracket (time frame: Up to Month 12). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04851873, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2024.

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