A Phase 1 interventional study of AVXS-101 in Spinal Muscular Atrophy 1, sponsored by Novartis Gene Therapies. Completed at 1 site in United States. Open to participants aged Up to 6 Months. Per ClinicalTrials.gov, last updated 2022-09-15.
Sponsored by Novartis Gene Therapies · Phase 1, Interventional, and Treatment
The purpose of this trial is to evaluate safety and efficacy of intravenous delivery of AVXS-101 as a treatment of spinal muscular atrophy Type 1 (SMN1).
The study will evaluate safety and efficacy of gene therapy in spinal muscular atrophy Type 1 (SMA1) patients. SMA is caused by low levels of the survival motor neuron (SMN) protein, and affects all muscles in the body. There is no effective treatment for SMA and current drug therapy has been unsuccessful in stabilizing or reversing this disease. Only supportive care is currently possible.
Open-label, dose-escalation clinical trial of AVXS-101 injected intravenously through a peripheral limb vein. Short-term safety will be evaluated over a two year period. Patients will be tested at baseline and return for follow up visits on days 7, 14, 21, 30, followed by once every month through 12 months post dose, and then every three months through two (2) years post infusion. Unscheduled visits may occur if the PI determines that they are necessary.
The primary analysis for efficacy will be assessed when all patients reach 13.6 months of age (a database lock will be performed at the time point at which all patients reach 13.6 months of age). A follow-up safety analysis will be completed at the time point at which the last patient reaches 24 months post-dose.
Upon completion of the 2-year study period, patients will be monitored annually as per standard of care for up to 15 years.
494 studies on the registry are indexed under Muscular Atrophy; 94 are open to participants now.
This study's enrollment of 15 is below the median of 33 across 335 interventional studies indexed under Muscular Atrophy.
Browse Muscular Atrophy studies →Novartis Gene Therapies is the lead sponsor of 8 studies on the registry; none are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 5 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Six or nine months of age and younger (depending on cohort) on day of vector infusion with Type 1 SMA as defined by the following features:
Exclusion Criteria:
6.7 X 10\^13 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=3)
Biological: AVXS-101
2.0 X 10\^14 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=12)
Biological: AVXS-101
Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter
Also known as: Zolgensma
Number of Participants That Experienced One Grade III or Higher Unanticipated, Treatment-related Toxicity That Presents With Clinical Symptoms and Requires Medical Treatment
Time frame: 2 years
Number of Participants Who Experienced Permanent Ventilation or Death
Permanent ventilation was defined as the requirement of ≥ 16-hour respiratory assistance, including non-invasive ventilatory support, per day continuously for ≥ 2 weeks in the absence of an acute reversible illness, excluding perioperative ventilation.
Time frame: Up to 13.6 months of age
Percent Change From Baseline in Mean Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) Score
Score ranges from 0 to 64, where 64 is the maximum possible score. A higher score is indicative of higher/better motor function. CHOP-INTEND assessments were discontinued once patients achieved higher functioning status, so the number of available data points decreased over time.
Time frame: Baseline to 24 months post-dose
Number of Participants With Assessed Improvement in Motor Function
Improvement in motor function was determined by achievement of developmental milestones, specifically achievement of ability to sit unassisted for at least 30 seconds, determined by physical therapist and confirmed by an independent central video reviewer. Achievement of functional independent sitting was defined as the ability to maintain a sitting position independently for at least 30 seconds as confirmed per video evaluation by an expert central reviewer based on videos taken either at scheduled visits or provided by the parent/legal guardian.
Time frame: 24 months post-dose
Recruitment period May 2014 - Dec 2015
| Milestone | Cohort 1 | Cohort 2 |
|---|---|---|
| Started | 3 | 12 |
| Completed | 3 | 12 |
| Not completed | 0 | 0 |
| Participants | Cohort 1 | Cohort 2 |
|---|---|---|
| Number of Participants That Experienced One Grade III or Higher Unanticipated, Treatment-related Toxicity That Presents With Clinical Symptoms and Requires Medical Treatment | 1 | 3 |
Permanent ventilation was defined as the requirement of ≥ 16-hour respiratory assistance, including non-invasive ventilatory support, per day continuously for ≥ 2 weeks in the absence of an acute reversible illness, excluding perioperative ventilation.
| Participants | Cohort 1 | Cohort 2 |
|---|---|---|
| Number of Participants Who Experienced Permanent Ventilation or Death | 0 | 0 |
Score ranges from 0 to 64, where 64 is the maximum possible score. A higher score is indicative of higher/better motor function. CHOP-INTEND assessments were discontinued once patients achieved higher functioning status, so the number of available data points decreased over time.
| Percentage Change | Cohort 1 | Cohort 2 |
|---|---|---|
| Percent Change From Baseline in Mean Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) Score | — | 30.7 ± 145.61 |
Improvement in motor function was determined by achievement of developmental milestones, specifically achievement of ability to sit unassisted for at least 30 seconds, determined by physical therapist and confirmed by an independent central video reviewer. Achievement of functional independent sitting was defined as the ability to maintain a sitting position independently for at least 30 seconds as confirmed per video evaluation by an expert central reviewer based on videos taken either at scheduled visits or provided by the parent/legal guardian.
| Participants | Cohort 1 | Cohort 2 |
|---|---|---|
| Number of Participants With Assessed Improvement in Motor Function | 0 | 9 |
Collected over Adverse events were collected from the single dose of study treatment until 24 months post dose. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1 | 0/3 (0%) | 3/3 (100%) | 3/3 (100%) |
| Cohort 2 | 0/12 (0%) | 10/12 (83.3%) | 12/12 (100%) |
| Event | Cohort 1 | Cohort 2 |
|---|---|---|
| pneumoniaInfections and infestations | 0/3 | 7/12 |
| parainfluenzae virus infectionInfections and infestations | 1/3 | 2/12 |
| respiratory syncytial virus bronchiolitisInfections and infestations | 1/3 | 2/12 |
| transaminases increasedInvestigations | 1/3 | 1/12 |
| bronchitisInfections and infestations | 1/3 | 0/12 |
| influenzaInfections and infestations | 1/3 | 0/12 |
| respiratory failureRespiratory, thoracic and mediastinal disorders | 1/3 | 0/12 |
| pneumonia respiratory syncytial viralInfections and infestations | 1/3 | 2/12 |
| upper respiratory tract infectionInfections and infestations | 0/3 | 3/12 |
| rhinovirus infectionInfections and infestations | 0/3 | 2/12 |
| Event | Cohort 1 | Cohort 2 |
|---|---|---|
| upper respiratory tract infectionInfections and infestations | 1/3 | 9/12 |
| vomitingGastrointestinal disorders | 0/3 | 8/12 |
| otitis mediaInfections and infestations | 2/3 | 2/12 |
| pyrexiaGeneral disorders | 1/3 | 7/12 |
| constipationGastrointestinal disorders | 1/3 | 6/12 |
| nasal congestionRespiratory, thoracic and mediastinal disorders | 0/3 | 6/12 |
| gastroesophageal reflux diseaseGastrointestinal disorders | 1/3 | 5/12 |
| gastroenteritis viralInfections and infestations | 0/3 | 5/12 |
| coughRespiratory, thoracic and mediastinal disorders | 0/3 | 5/12 |
| rashSkin and subcutaneous tissue disorders | 0/3 | 5/12 |
| Age, Categorical(Participants) | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| <=18 years | 3 | 12 | 15 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(months) | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Mean | 6.33 ± 0.751 | 3.42 ± 2.063 | 4.00 ± 2.209 |
| Sex: Female, Male(Participants) | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Female | 2 | 7 | 9 |
| Male | 1 | 5 | 6 |
| Race/Ethnicity, Customized(Participants) | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Not Hispanic or Latino | 3 | 10 | 13 |
| Hispanic or Latino | 0 | 2 | 2 |
| Region of Enrollment(participants) | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| United States | 3 | 12 | 15 |
| SMN2 copy number = 2(Participants) | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Count of participants | 3 | 12 | 15 |
| bi-allelic deletions of SMN1(Participants) | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Count of participants | 3 | 12 | 15 |
| Exon 7 gene modifier mutation(Participants) | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Count of participants | 0 | 0 | 0 |
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Novartis Gene Therapies