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 : Completed
First Posted : February 12, 2019
Results First Posted : January 11, 2022
Last Update Posted : November 22, 2022
|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 (Clinical Trial)|
|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 31, 2019|
|Actual Primary Completion Date :||June 29, 2021|
|Actual Study Completion Date :||June 29, 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.
Other Name: Zolgensma
- Number of Participants Who Achieved Sitting Alone for at Least 10 Seconds [ Time Frame: From Baseline up to 18 Months of Age Visit ]Independent sitting is defined by the World Health Organization Multicentre Growth Reference Study, confirmed by video recording, as a participant who sits up straight unsupported for at least 10 seconds.
- Event-free Survival at 14 Months of Age [ Time Frame: From Baseline up to 14 Months of Age ]Event-free survival at 14 months of age was defined as the number of participants who did not die, did not require permanent ventilation and did not withdraw from the study by 14 months of age.
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:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|