Single-Dose Gene Replacement Therapy Clinical Trial for Participants With Spinal Muscular Atrophy Type 1 (STRIVE-EU)
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| ClinicalTrials.gov Identifier: NCT03461289 |
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Recruitment Status :
Completed
First Posted : March 12, 2018
Results First Posted : April 2, 2021
Last Update Posted : August 16, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| SMA | Biological: Onasemnogene Abeparvovec-xioi | Phase 3 |
Phase 3, open-label, single-arm, single-dose, trial of onasemnogene abeparvovec-xioi (gene replacement therapy) in patients with spinal muscular atrophy (SMA) Type 1 who meet enrollment criteria and are genetically defined by a biallelic pathogenic mutation of the survival motor neuron 1 gene (SMN1) with one or two copies of survival motor neuron 2 gene (SMN2). 30 patients < 6 months (< 180 days) of age at the time of gene replacement therapy (Day 1) will be enrolled.
The trial includes a screening period, a gene replacement therapy period, and a follow-up period. During the screening period (Days -30 to -2), patients whose parent(s)/legal guardian(s) provide informed consent will complete screening procedures to determine eligibility for trial enrollment. Patients who meet the entry criteria will enter the in-patient gene replacement therapy period (Day -1 to Day 3). On Day -1, patients will be admitted to the hospital for pre-treatment baseline procedures. On Day 1, patients will receive a one-time intravenous (IV) infusion of onasemnogene abeparvovec-xioi, and will undergo in-patient safety monitoring over the next 48 hours. Patients may be discharged 48 hours after the infusion, based on Investigator judgment. During the outpatient follow-up period (Days 4 to End of Trial at 18 months of age), patients will return at regularly scheduled intervals for efficacy and safety assessments until the End of Trial when the patient reaches 18 months of age. After the End of Trial visit, eligible patients will be asked to participate into the long-term follow up trial.
All post-treatment visits will be relative to the date on which gene replacement therapy is administered, until the patient is 14 months of age, after which they will be relevant to the patient's date of birth.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 33 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Intervention Model Description: | Open-label, single-arm, single-dose, trial of onasemnogene abeparvovec-xioi |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase 3, Open-Label, Single-Arm, Single-Dose Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies Delivering AVXS-101 by Intravenous Infusion |
| Actual Study Start Date : | August 16, 2018 |
| Actual Primary Completion Date : | September 11, 2020 |
| Actual Study Completion Date : | September 11, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Onasemnogene Abeparvovec-xioi
Onasemnogene abeparvovec-xioi is a non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the human survival motor neuron (SMN) gene under the control of the cytomegalovirus (CMV) enhancer/chicken β-actin-hybrid promoter (CB).
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Biological: Onasemnogene Abeparvovec-xioi
Onasemnogene abeparvovec-xioi is a non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the human survival motor neuron (SMN) gene under the control of the cytomegalovirus (CMV) enhancer/chicken β-actin-hybrid promoter (CB).
Other Names:
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- Number of Participants Who Achieve Independent Sitting for at Least 10 Seconds [ Time Frame: From Day 1 up to 18 Months of Age Visit (Up to a Maximum of Approximately 17 Months) ]Independent sitting is defined by the World Health Organization Multicentre Growth Reference Study, confirmed by video recording, as a participant who sits up straight with head erect for at least 10 seconds; participant does not use arms or hands to balance body or support position.
- Event-free Survival at 14 Months of Age [ Time Frame: Up to 14 months of age ]Event-free survival at 14 months of age was defined as the number of participants who did not die, did not require permanent ventilation and did not withdraw from the study by 14 months of age.
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| Ages Eligible for Study: | up to 6 Months (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients with SMA Type 1 as determined by diagnosis of SMA based on gene mutation analysis with biallelic SMN1 mutations (deletion or point mutations) and one or two copies of SMN2 [inclusive of the known SMN2 gene modifier mutation (c.859G>C)]
- Patients must be < 6 months (< 180 days) of age at the time of onasemnogene abeparvovec-xioi infusion
- Patients must have a swallowing evaluation test performed prior to administration of gene replacement therapy
Exclusion Criteria:
- Previous, planned or expected scoliosis repair surgery/procedure prior to 18 months of age
- Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry < 95% saturation at screening
- Use or requirement of non-invasive ventilatory support for 12 or more hours daily in the two weeks prior to dosing
- Patient with signs of aspiration based on a swallowing test or whose weight-for-age falls below the 3rd percentile based on World Health Organization (WHO) Child Growth Standards and unwilling to use an alternative method to oral feeding
- Participation in recent SMA treatment clinical trial (with the exception of observational cohort studies or non-interventional studies) or receipt of an investigational or commercial compound, product or therapy administered with the intent to treat SMA (eg, nusinersen, valproic acid,) at any time prior to screening for this trial.
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): NCT03461289
| Belgium | |
| University Hospital Ghent Neuromuscular reference center | |
| Ghent, Belgium | |
| Neuropédiatrie - Centre de Référence des Maladies Neuromusculaires | |
| Liège, Belgium | |
| France | |
| Hôpital Armand Trousseau | |
| Paris, France | |
| Italy | |
| Istituto Gianninia Gaslini | |
| Genova, Italy | |
| Policlinico "G. Martino" | |
| Messina, Italy | |
| Carlo Besta Neurological Research Institute | |
| Milan, Italy | |
| University of Milan | |
| Milan, Italy | |
| Policlinico Gemelli | |
| Rome, Italy | |
| United Kingdom | |
| Great Ormond Street Hospital for Children | |
| London, United Kingdom | |
| The John Walton Muscular Dystrophy Research Centre MRC Centre for Neuromuscular Diseases at Newcastle | |
| Newcastle Upon Tyne, United Kingdom | |
| Study Chair: | AveXis Medinfo | Sponsor GmbH |
Documents provided by Novartis ( Novartis Gene Therapies ):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Novartis Gene Therapies |
| ClinicalTrials.gov Identifier: | NCT03461289 |
| Other Study ID Numbers: |
AVXS-101-CL-302 2017-000266-29 ( EudraCT Number ) COAV101A12301 ( Other Identifier: Novartis Pharmaceuticals ) |
| First Posted: | March 12, 2018 Key Record Dates |
| Results First Posted: | April 2, 2021 |
| Last Update Posted: | August 16, 2022 |
| Last Verified: | August 2022 |
| 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/. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
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Muscular Atrophy Muscular Atrophy, Spinal Atrophy Spinal Cord Diseases Pathological Conditions, Anatomical Neuromuscular Manifestations |
Neurologic Manifestations Nervous System Diseases Central Nervous System Diseases Motor Neuron Disease Neurodegenerative Diseases Neuromuscular Diseases |