Single-Dose Gene Replacement Therapy Using for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies
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|ClinicalTrials.gov Identifier: NCT03837184|
Recruitment Status : Active, not recruiting
First Posted : February 12, 2019
Last Update Posted : March 30, 2021
|Condition or disease||Intervention/treatment||Phase|
|Spinal Muscular Atrophy Type I||Biological: Onasemnogene Abeparvovec-xioi||Phase 3|
This is a Phase 3, open-label, single-arm, single-dose trial of onasemnogene abeparvovec-xioi (gene replacement therapy) in participants with SMA Type 1 with one or 2 copies of SMN2. At least 6 participants < 6 months (< 180 days) of age at the time of gene replacement therapy (Day 1) will be enrolled.
The trial includes 3 trial periods: screening, gene replacement therapy, and follow-up. During the screening period (Days -30 to -2), participants whose parent(s)/legal guardian(s) provide informed consent will undergo screening procedures to determine eligibility for trial enrollment. participants who meet the entry criteria will enter the in-patient gene replacement therapy period (Day -1 to Day 3). On Day -1, participants will be admitted to the hospital for pre-treatment baseline procedures. On Day 1, participants will receive a one-time intravenous (IV) infusion of the equivalent of onasemnogene abeparvovec-xioi cohort 2 dose received in the AVXS-101-CL-101 trial over approximately 60 minutes and will undergo in-patient safety monitoring over the next 48 hours. Participants may be discharged 48 hours after gene replacement therapy, based on Investigator judgment. During the outpatient follow-up period (Days 4 to End of Trial at 18 months of age), participants will return at regularly scheduled intervals for efficacy and safety assessments until the participant reaches 18 months of age.
|Study Type :||Interventional|
|Actual Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 :||May 15, 2019|
|Estimated Primary Completion Date :||June 22, 2021|
|Estimated Study Completion Date :||June 22, 2021|
Experimental: Onasemnogene Abeparvovec-xioi
Participants will receive a single dose of onasemnogene abeparvovec-xioi, administered intravenously.
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). Onasemnogene abeparvovec-xioi will be administered as a one-time intravenous infusion over approximately 60 minutes. Dosage will be determined by the participants weight.
- Proportion of Participants Sitting Without Support [ Time Frame: Up to 18 Months of Age Visit (Up To 14 Days After Participant Reaches 18 Months of Age) ]The proportion of symptomatic SMA Type 1 participants who are homozygous negative for SMN1 exon 7 and have 2 copies of SMN2 without the SMN2 genetic modifier that achieve the ability to sit without support for at least 10 seconds. 'Sitting without support' is defined by the WHO Multicentre Growth Reference Study as "a patient who sits up straight with head erect for at least 10 seconds; child does not use arms or hands to balance body or support position".
- Proportion of Participants Surviving [ Time Frame: 14 Months of Age Visit (Up To 14 Days After Participant Reaches 18 Months of Age) ]The proportion of participants at 14 months of age amongst symptomatic SMA Type 1 participants who are homozygous negative for SMN1 exon 7 and have 2 copies of SMN2 without the SMN2 genetic modifier. 'Survival' is defined as the avoidance of the combined endpoint of either (a) death or (b) permanent ventilation, which is defined by tracheostomy or by the requirement of ≥ 16 hours of respiratory assistance per day (via non-invasive ventilatory support) for ≥ 14 consecutive days in the absence of an acute reversible illness, excluding perioperative ventilation. Permanent ventilation, so defined, is considered a surrogate for death.
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): NCT03837184
|Tokyo Women's Medical University|
|Korea, Republic of|
|Pusan National University Yangsan Hospital|
|Yangsan, Gyeongsangnam-do, Korea, Republic of|
|Seoul National University Hospital|
|Seoul, Korea, Republic of|
|National Taiwan University Hospital|
|Study Director:||Medical Director||Novartis Gene Therapies, Inc.|