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Single-Dose Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1 (STRIVE-EU)

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ClinicalTrials.gov Identifier: NCT03461289
Recruitment Status : Not yet recruiting
First Posted : March 12, 2018
Last Update Posted : June 26, 2018
Sponsor:
Information provided by (Responsible Party):
AveXis, Inc.

Brief Summary:
Phase 3, open-label, single-arm, single-dose, trial of AVXS-101 (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). Up to 30 patients < 6 months (< 180 days) of age at the time of gene replacement therapy (Day 1) will be enrolled.

Condition or disease Intervention/treatment Phase
SMA Biological: AVXS-101 Phase 3

Detailed Description:

Phase 3, open-label, single-arm, single-dose, trial of AVXS-101 (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). Up to 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 AVXS-101, 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 rollover into the long-term follow up trial.

All post-treatment visits will be relative to the date on which gene replacement therapy is administered, except for the 14 and 18 months of age visits, which will be relative to the patient's date of birth.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Open-label, single-arm, single-dose, trial of AVXS-101
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: European, 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
Estimated Study Start Date : June 2018
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020


Arm Intervention/treatment
Experimental: AVXS-101
AVXS-101 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).
Biological: AVXS-101
AVXS-101 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).




Primary Outcome Measures :
  1. Sitting without support [ Time Frame: Through 18 months of age ]
    Proportion of patients achieving the developmental milestone of sitting without support up to 18 months of age


Secondary Outcome Measures :
  1. Survival [ Time Frame: Through 14 months of age ]
    Proportion of patients survivingl at 14 months of age



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 6 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 AVXS-101 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 [27] 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.

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): NCT03461289


Contacts
Contact: AveXis Medinfo 833-828-3947 medinfo@avexis.com

Locations
Belgium
University Hospital Ghent Neuromuscular reference center Not yet recruiting
Ghent, Belgium
Contact: Elke Devos       elke.devos@uzgent.be   
Neuropédiatrie - Centre de Référence des Maladies Neuromusculaires Not yet recruiting
Liège, Belgium
Contact: Anne-Catherine Defeldre       Anne.Catherine.Defeldre@chrcitadelle.be   
France
Hôpital Armand Trousseau Not yet recruiting
Paris, France
Contact: Arnaud Jollet       a.jollet@institut-myologie.org   
Germany
Centre for Neuromuscular Disorders in children and adolescents University Clinic Essen, Childrens´ hospital
Essen, Germany
Klinik für Neuropädiatrie und Muskelerkrankungen Not yet recruiting
Freiburg, Germany
Contact: Sabine Wider       sabine.wider@uniklinik-freiburg.de   
Kinderklinik und Kinderpoliklinik der Ludwig Maximilian Universität Not yet recruiting
München, Germany
Contact: Christiane Eder       Christiane.Eder@med.uni-muenchen.de   
Italy
Istituto Gianninia Gaslini Not yet recruiting
Genova, Italy
Contact: Marina Pedemonte       marinapedemonte@gaslini.org   
Policlinico "G. Martino" Not yet recruiting
Messina, Italy
Contact: Daniela Quattrocchi       daniela.quattrocchigl@gmail.com   
Carlo Besta Neurological Research Institute Not yet recruiting
Milan, Italy
Contact: Angelina Campanella       Angela.Campanella@istituto-besta.it   
University of Milan Not yet recruiting
Milan, Italy
Contact: Alessandra Govoni       alessandra.govoni@policlinico.mi.it   
Policlinico Gemelli Not yet recruiting
Rome, Italy
Contact: Maria Rosaria Vizino       mariarosaria.vizzino@guest.policlinicogemelli.it   
Netherlands
UMC Utrecht Wilhelmina Kinderziekenhui Not yet recruiting
Utrecht, Netherlands
Contact: Fay-Lynn Asselman       F.Asselman@umcutrecht.nl   
Spain
Area Genetica Clínica y Molecular Not yet recruiting
Barcelona, Spain
Contact: Scherezade Sarri       scherezade.sarri@vhir.org   
Sweden
Gothenburg University Queen Silvia Children's Hospital Not yet recruiting
Gothenburg, Sweden
Contact: Anna-Lena Tulinius       anna-lena.tulinius@vgregion.se   
United Kingdom
Great Ormond Street Hospital for Children Not yet recruiting
London, United Kingdom
Contact: Hinal Patel       hinal.patel@ucl.ac.uk   
The John Walton Muscular Dystrophy Research Centre MRC Centre for Neuromuscular Diseases at Newcastle Not yet recruiting
Newcastle Upon Tyne, United Kingdom
Contact: Anna Peel       Anna.peel1@newcastle.ac.uk   
Sponsors and Collaborators
AveXis, Inc.
Investigators
Study Chair: AveXis Medinfo Sponsor GmbH

Additional Information:
Responsible Party: AveXis, Inc.
ClinicalTrials.gov Identifier: NCT03461289     History of Changes
Other Study ID Numbers: AVXS-101-CL-302
First Posted: March 12, 2018    Key Record Dates
Last Update Posted: June 26, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Atrophy
Muscular Atrophy
Muscular Atrophy, Spinal
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases