NCT02122952

Brief Summary

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started May 2014

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 23, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 25, 2014

Completed
10 days until next milestone

Study Start

First participant enrolled

May 5, 2014

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 15, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 15, 2017

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

May 10, 2019

Completed
Last Updated

September 15, 2022

Status Verified

August 1, 2022

Enrollment Period

3.6 years

First QC Date

April 23, 2014

Results QC Date

July 20, 2018

Last Update Submit

August 30, 2022

Conditions

Spinal Muscular Atrophy 1

Keywords

Gene TransferGene TherapyAdeno-associated virusSurvival Motor NeuronSMNAAV9

Outcome Measures

Primary Outcomes (1)

  • Number of Participants That Experienced One Grade III or Higher Unanticipated, Treatment-related Toxicity That Presents With Clinical Symptoms and Requires Medical Treatment

    2 years

Secondary Outcomes (3)

  • Number of Participants Who Experienced Permanent Ventilation or Death

    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

    Baseline to 24 months post-dose

  • Number of Participants With Assessed Improvement in Motor Function

    24 months post-dose

Study Arms (2)

Cohort 1

EXPERIMENTAL

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

Cohort 2

EXPERIMENTAL

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

Interventions

AVXS-101BIOLOGICAL

Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

Also known as: Zolgensma
Cohort 1Cohort 2

Eligibility Criteria

AgeUp to 6 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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:
  • Diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and 2 copies of SMN2.
  • Onset of disease at birth up to 6 months of age.
  • Hypotonia by clinical evaluation with delay in motor skills, poor head control, round shoulder posture and hypermobility of joints.

You may not qualify if:

  • Active viral infection (includes HIV or serology positive for hepatitis B or C)
  • Use of invasive ventilatory support (tracheotomy with positive pressure)\* or pulse oximetry \<95% saturation.
  • Patients may be put on non-invasive ventilator support (BiPAP) for less than 16 hours a day at the discretion of their physician or research staff.
  • Concomitant illness that in the opinion of the PI creates unnecessary risks for gene transfer
  • Concomitant use of any of the following drugs: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy or immunosuppressive therapy within 3 months of starting the trial (e.g. corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab)
  • Patients with Anti-AAV9 antibody titers \>1:50 as determined by ELISA binding immunoassay.
  • Abnormal laboratory values considered clinically significant (GGT \> 3XULN, bilirubin ≥ 3.0 mg/dL , creatinine ≥ 1.8 mg/dL, Hgb \< 8 or \> 18 g/Dl; WBC \> 20,000 per cmm) Participation in a recent SMA treatment clinical trial that in the opinion of the PI creates unnecessary risks for gene transfer.
  • Family does not want to disclose patient's study participation with primary care physician and other medical providers.
  • Patient with signs of aspiration based on a swallowing test and unwilling to use an alternative method to oral feeding.
  • Patients with a single base substitution in SMN2 (c.859G\>C in exon 7) will be excluded based on predicted mild phenotype.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (9)

  • Bevan AK, Duque S, Foust KD, Morales PR, Braun L, Schmelzer L, Chan CM, McCrate M, Chicoine LG, Coley BD, Porensky PN, Kolb SJ, Mendell JR, Burghes AH, Kaspar BK. Systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disorders. Mol Ther. 2011 Nov;19(11):1971-80. doi: 10.1038/mt.2011.157. Epub 2011 Aug 2.

    PMID: 21811247BACKGROUND

  • Bevan AK, Hutchinson KR, Foust KD, Braun L, McGovern VL, Schmelzer L, Ward JG, Petruska JC, Lucchesi PA, Burghes AH, Kaspar BK. Early heart failure in the SMNDelta7 model of spinal muscular atrophy and correction by postnatal scAAV9-SMN delivery. Hum Mol Genet. 2010 Oct 15;19(20):3895-905. doi: 10.1093/hmg/ddq300. Epub 2010 Jul 16.

    PMID: 20639395BACKGROUND

  • Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, Le TT, Morales PR, Rich MM, Burghes AH, Kaspar BK. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol. 2010 Mar;28(3):271-4. doi: 10.1038/nbt.1610. Epub 2010 Feb 28.

    PMID: 20190738BACKGROUND

  • Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol. 2009 Jan;27(1):59-65. doi: 10.1038/nbt.1515. Epub 2008 Dec 21.

    PMID: 19098898BACKGROUND

  • Day JW, Mendell JR, Mercuri E, Finkel RS, Strauss KA, Kleyn A, Tauscher-Wisniewski S, Tukov FF, Reyna SP, Chand DH. Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy. Drug Saf. 2021 Oct;44(10):1109-1119. doi: 10.1007/s40264-021-01107-6. Epub 2021 Aug 12.

    PMID: 34383289DERIVED

  • Lowes LP, Alfano LN, Arnold WD, Shell R, Prior TW, McColly M, Lehman KJ, Church K, Sproule DM, Nagendran S, Menier M, Feltner DE, Wells C, Kissel JT, Al-Zaidy S, Mendell J. Impact of Age and Motor Function in a Phase 1/2A Study of Infants With SMA Type 1 Receiving Single-Dose Gene Replacement Therapy. Pediatr Neurol. 2019 Sep;98:39-45. doi: 10.1016/j.pediatrneurol.2019.05.005. Epub 2019 May 13.

    PMID: 31277975DERIVED

  • Dabbous O, Maru B, Jansen JP, Lorenzi M, Cloutier M, Guerin A, Pivneva I, Wu EQ, Arjunji R, Feltner D, Sproule DM. Survival, Motor Function, and Motor Milestones: Comparison of AVXS-101 Relative to Nusinersen for the Treatment of Infants with Spinal Muscular Atrophy Type 1. Adv Ther. 2019 May;36(5):1164-1176. doi: 10.1007/s12325-019-00923-8. Epub 2019 Mar 16.

    PMID: 30879249DERIVED

  • Al-Zaidy S, Pickard AS, Kotha K, Alfano LN, Lowes L, Paul G, Church K, Lehman K, Sproule DM, Dabbous O, Maru B, Berry K, Arnold WD, Kissel JT, Mendell JR, Shell R. Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy. Pediatr Pulmonol. 2019 Feb;54(2):179-185. doi: 10.1002/ppul.24203. Epub 2018 Dec 12.

    PMID: 30548438DERIVED

  • Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, Lowes L, Alfano L, Berry K, Church K, Kissel JT, Nagendran S, L'Italien J, Sproule DM, Wells C, Cardenas JA, Heitzer MD, Kaspar A, Corcoran S, Braun L, Likhite S, Miranda C, Meyer K, Foust KD, Burghes AHM, Kaspar BK. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1713-1722. doi: 10.1056/NEJMoa1706198.

    PMID: 29091557DERIVED

Related Links

MeSH Terms

Conditions

Spinal Muscular Atrophies of Childhood

Interventions

Zolgensma

Condition Hierarchy (Ancestors)

Muscular Atrophy, SpinalSpinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesMotor Neuron DiseaseNeuromuscular DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

Link to the full study results: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17849

Results Point of Contact

Title
Doug Feltner, MD
Organization
AveXis, Inc.
medinfo@avexis.com
833-828-3947

Study Officials

  • Jerry R Mendell, MD

    The Research Institute at Nationwide Children's Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 23, 2014

First Posted

April 25, 2014

Study Start

May 5, 2014

Primary Completion

December 15, 2017

Study Completion

December 15, 2017

Last Updated

September 15, 2022

Results First Posted

May 10, 2019

Record last verified: 2022-08

Locations

US(1)