Pre-Symptomatic Study of Intravenous AVXS-101 in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2



Status:Recruiting
Conditions:Neurology, Neurology, Orthopedic
Therapuetic Areas:Neurology, Orthopedics / Podiatry
Healthy:No
Age Range:Any
Updated:4/6/2019
Start Date:April 10, 2018
End Date:June 2023
Contact:AveXis MedInfo
Email:medinfo@avexis.com
Phone:833-828-3947

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A Global Study of a Single, One-Time Dose of AVXS-101 Delivered to Infants With Genetically Diagnosed and Pre-symptomatic Spinal Muscular Atrophy With Multiple Copies of SMN2

To evaluate the safety and efficacy of intravenous AVXS-101 in pre-symptomatic patients with
SMA and 2 or 3 copies SMN2

Phase 3, open-label, single-arm study of a single, one-time dose of AVXS-101 (gene
replacement therapy) in patients with spinal muscular atrophy who meet enrollment criteria
and are genetically defined by bi-allelic deletion of survival motor neuron 1 gene (SMN1)
with 2 or 3 copies of survival motor neuron 2 gene (SMN2). Patients with SMN1 point mutations
or the SMN2 gene modifier mutation (c.859G>C) may enroll but will not be included in the
efficacy analysis sets.

The study 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 undergo screening procedures to determine
eligibility for study enrollment. Patients who meet the entry criteria will enter the
in-patient gene replacement therapy period (Day -1 to Day 2). On Day -1, patients will be
admitted to the hospital for pre-treatment baseline procedures. On Day 1, patients will
receive a single, one-time intravenous (IV) infusion of AVXS-101, and will undergo in-patient
safety monitoring for a minimum of 24 hours post infusion. Patients may be discharged 24
hours after the infusion, based on Investigator judgment. During the outpatient follow-up
period (Days 3 to End of Study at 18 or 24 of age, dependent upon respective SMN2 copy
number), patients will return at regularly scheduled intervals for efficacy and safety
assessments until the End of Study when the patient reaches 18 months of age (SMN2 = 2) or 24
months of age (SMN2 = 3). After the End of Study visit, eligible patients will be asked to
rollover into a long-term follow up study.

Inclusion Criteria:

- Age ≤6 weeks (≤42 days) at time of dose

- Ability to tolerate thin liquids as demonstrated through a formal bedside swallowing
test

- Compound muscle action potential (CMAP) ≥2mV at Baseline; centralized review of CMAP
data will be conducted

- Gestational age of 35 to 42 weeks

- Patients with pre-symptomatic SMA Type 1 as determined by the following features:

− 2 copies of SMN2 Patients with 2 copies of SMN2 (n ≥12)

- Patients with pre-symptomatic SMA Type 2 as determined by the following features:

- 3 copies of SMN2

Exclusion Criteria:

- Weight at screening visit <2 kg

- Hypoxemia (oxygen saturation <96% awake or asleep without any supplemental oxygen or
respiratory support) at the screening visit or for altitudes >1000 m, oxygen
saturation <92% awake or asleep without any supplemental oxygen or respiratory support
at the screening visit

- Any clinical signs or symptoms at screening or immediately prior to dosing that are,
in the opinion of the Investigator, strongly suggestive of SMA

- Tracheostomy or current prophylactic use or requirement of noninvasive ventilatory
support at any time and for any duration prior to screening or during the screening
period

- Patients with signs of aspiration/inability to tolerate nonthickened liquids based on
a formal swallowing test performed as part of screening or patients receiving any
non-oral feeding method

- Clinically significant abnormalities in hematology or clinical chemistry parameters as
determined by investigator or medical monitor

- Treatment with an investigational or commercial product, including nusinersen, given
for the treatment of SMA. This includes any history of gene therapy, prior antisense
oligonucleotide treatment, or cell transplantation.

- Patients whose weight-for-age is below the third percentile based on World Health
Organization (WHO) Child Growth Standards

- Biological mother with active viral infection as determined by screening laboratory
samples (includes human immunodeficiency virus [HIV] or positive serology for
hepatitis B or C)

• Biological mothers with clinical suspicion of Zika virus that meet Centers for
Disease Control and Prevention (CDC) Zika virus epidemiological criteria including
history of residence in or travel to a geographic region with active Zika transmission
at the time of travel will be tested for Zika virus RNA. Positive results warrant
confirmed negative Zika virus RNA testing in the patient prior to enrollment.

- Serious nonrespiratory tract illness requiring systemic treatment and/or
hospitalization within 2 Weeks prior to screening

- Upper or lower respiratory infection requiring medical attention, medical
intervention, or increase in supportive care of any manner within 4 Weeks prior to
dosing

- Severe nonpulmonary/respiratory tract infection within 4 Weeks before administration
of gene replacement therapy or concomitant illness that, in the opinion of the
Investigator or Sponsor medical monitor, creates unnecessary risks for gene
replacement therapy such as:

- Major renal or hepatic impairment

- Known seizure disorder

- Diabetes mellitus

- Idiopathic hypocalciuria

- Symptomatic cardiomyopathy

- Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or
their excipients

- Previous, planned or expected major surgical procedure including scoliosis repair
surgery/procedure during the study assessment period

- Concomitant use of any of the following: drugs for treatment of myopathy or
neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive
therapy, plasmapheresis, immunomodulators such as adalimumab, immunosuppressive
therapy within 4 Weeks prior to gene replacement therapy

- AntiAAV9 antibody titer >1:50 as determined by Enzyme-linked Immunosorbent Assay
(ELISA) binding immunoassay

• Should a potential patient demonstrate AntiAAV9 antibody titer >1:50, he or she may
receive retesting inside the 30-Day screening period and will be eligible to
participate if the AntiAAV9 antibody titer upon retesting is ≤1:50, provided the <6
Week age requirement at the time of dosing is still met

- Biological mother involved with the care of the child refuses anti-AAV9 antibody
testing prior to dosing
We found this trial at
17
sites
201 Presidents Circle
Salt Lake City, Utah 84108
801) 581-7200
Principal Investigator: Nicholas Butterfield, MD
Phone: 801-581-3724
University of Utah Research is a major component in the life of the U benefiting...
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185 Cambridge Street
Boston, Massachusetts 02114
617-724-5200
Principal Investigator: Kathryn Swoboda, MD
Phone: 617-724-2523
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Boston, MA
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700 Childrens Drive
Columbus, Ohio 43205
(616) 722-2000
Principal Investigator: Jerry R Mendell, M.D.
Phone: 614-355-2606
Nationwide Children's Hospital At Nationwide Children’s, we are creating the future of pediatric health care....
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Columbus, OH
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116th St and Broadway
New York, New York 10027
(212) 854-1754
Principal Investigator: Claudia Chiriboga, MD
Phone: 212-342-3038
Columbia University In 1897, the university moved from Forty-ninth Street and Madison Avenue, where it...
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13123 E 16th Ave
Aurora, Colorado 80045
(720) 777-1234
Principal Investigator: Julie Parsons
Phone: 720-777-6895
Children's Hospital Colorado At Children's Hospital Colorado, we see more, treat more and heal more...
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Aurora, CO
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1801 Inwood Rd
Dallas, Texas 75390
(214) 645-3300
Principal Investigator: Susan Iannaccone, MD
Phone: 214-456-4426
University of Texas Southwestern Medical Center UT Southwestern is an academic medical center, world-renowned for...
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Dallas, TX
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Grand Rapids, Michigan 49503
Principal Investigator: Jena Krueger, MD
Phone: 616-391-5093
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Grand Rapids, MI
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10833 Le Conte Ave
Los Angeles, California 90095
(310) 825-4321
Principal Investigator: Perry Shieh, MD
Phone: 310-825-3264
David Geffen School of Medicine, UCLA In 2002 Mr. David Geffen announced a $200 million...
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Madison, Wisconsin 53706
(608) 263-2400
Principal Investigator: Jennifer Kwon, MD
Phone: 608-265-7814
University of Wisconsin-Madison In achievement and prestige, the University of Wisconsin-Madison has long been recognized...
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5600 Oakbrook Parkway
Norcross, Georgia 30093
Principal Investigator: Daniel Tarquinio, MD
Phone: 770-713-3653
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Norcross, GA
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Norfolk, Virginia 23502
Principal Investigator: Crystal Proud
Phone: 757-668-9356
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13535 Nemours Parkway
Orlando, Florida 32827
(407) 567-4000
Principal Investigator: Richard Finkel, MD
Phone: 407-650-7967
Nemours Children's Hospital Nemours Children's Hospital in Orlando brings pediatric specialty care never before offered...
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Randwick, New South Wales
Principal Investigator: Michelle Farrar
Phone: (02) 9382 5505
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Richmond, Virginia 23298
(804) 828-0100
Principal Investigator: Nicholas Johnson
Phone: 804-905-8361
Virginia Commonwealth University Since our founding as a medical school in 1838, Virginia Commonwealth University...
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660 South Euclid Avenue
Saint Louis, Missouri 63110
Principal Investigator: Craig Zaidman, MD
Phone: 314-362-2490
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Saint Louis, MO
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450 Serra Mall
Stanford, California 94305
(650) 723-2300
Principal Investigator: John Day, MD
Phone: 650-724-3792
Stanford University Stanford University, located between San Francisco and San Jose in the heart of...
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Strasburg, Pennsylvania 17579
Principal Investigator: Kevin Strauss, MD
Phone: 717-687-9407
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