Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)

Phase 3

Completed

• Conditions: Spinal Muscular Atrophy
• Interventions: Genetic: OAV101

• Registration Number: NCT04851873
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

To evaluate the safety, tolerability and efficacy of intravenous administration of OAV101 (AVXS-101) in patients with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene weighing ≥ 8.5 kg and ≤ 21 kg, over a 12 month period.

Detailed Description

This was an open-label, single arm, multi-center study designed to evaluate the safety, tolerability and efficacy of OAV101 in participants with SMA who weigh ≥ 8.5 kg and ≤ 21 kg. The study aimed to enroll approximately 24 to 30 participants, with approximately 6 to 10 participants across each of 3 weight brackets (8.5 to 13 kg, \>13 to 17 kg, \>17 to 21 kg).

Eligible participants received a single administration of OAV101 at the approved dose of 1.1e14 vg/kg on Day 1 (Treatment period), and were followed for a period of 12 months.

Participants were admitted to the hospital on Day -1 for pre-treatment baseline procedures. After receiving OAV101 on Day 1, participants underwent in-patient safety monitoring over the next 48 hours, after which the participant could be discharged, based on Investigator judgment.

After study completion, eligible participants could enroll into a Long Term follow-up study to collect additional safety and efficacy data. (COAV101A12308 (NCT05335876) https://classic.clinicaltrials.gov/ct2/show/NCT05335876?term=COAV101A12308\&draw=2\&rank=1))

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2021-04-06
• Study First Submitted QC: 2021-04-19
• Study First Posted: 2021-04-21
• Study Start: 2021-09-08
• Primary Completion: 2023-06-13
• Study Completion: 2023-06-13
• Results First Submitted: 2023-11-27
• Results First Submitted QC: 2024-01-03
• Results First Posted: 2024-01-05
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-07
• Last Update Posted: 2024-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
OAV101	OAV101	Participants received a single IV dose administration of OAV101

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Weight Bracket	Up to Month 12	An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.
Change From Baseline in Vital Signs Measurements - Systolic Blood Pressure (mmHg)	Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Change From Baseline in Vital Signs Measurements - Diastolic Blood Pressure (mmHg)	Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Change From Baseline in Vital Signs Measurements - Temperature (Degrees Celsius)	Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Change From Baseline in Vital Signs Measurements - Respiratory Rate (Breaths/Min)	Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52	Change from baseline in vital signs measurements - Respiratory Rate (breaths/min)
Change From Baseline in Vital Signs Measurements - Oxygen Saturation Level	Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52	Change from baseline in vital signs measurements - oxygen saturation level (%).; Oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated+saturated) in the blood and then multiplied by 100.
Number of Participants With Important Identified and Important Potential Risks (Adverse Events of Special Interest (AESI)) by Risk Name and Weight Bracket	Up to Month 12	Important identified and important potential risks included the following AESIs: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Dorsal root ganglia toxicity and Thrombotic microangiopathy.; These were assessed by the investigator.
Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Systolic and Diastolic Blood Pressure	12 months	Change from baseline in vital signs measurements - systolic and diastolic blood pressure (mmHg).; Systolic Blood Pressure-Low:\<=5th percentile of the age(Any Age), High:\>=90th percentile of the age, gender, and height group (\<18 yrs).; Diastolic Blood Pressure-High:\>=90th percentile of the age, gender, and height group(\<18 yrs).
Change From Baseline in Vital Signs Measurements - Pulse Rate (Beats/Min)	Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52	Change from baseline in vital signs measurements - Pulse Rate (beats/min
Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Temperature	12 months	Change from baseline in vital signs measurements - temperature (degrees Celsius); Temperature-Low:\<=35ºC(Any Age),High:\>=38.4ºC(\<18 yrs).

Secondary Outcome Measures

Name	Time	Method
Achievement of Development Motor Milestones According to the Modified and Combined WHO-MGRS and Bayley Scale of Infant and Toddler Development.	Baseline, Week 26 and Week 52	The World Health Organization-Multicentre Growth Reference Study (WHO-MGRS) and Bayley scale of Infant and Toddler Development was modified and combined into a single scale expressly for this study, to measure developmental motor milestones. These were assessed via the milestone checklist, formed of 10 yes/no questions with optional video documentation. The developmental milestones are: head control, sitting with support, sitting without support, sitting without support for 30 seconds, hands-and-knees crawling, pulls to stand, standing with assistance, walking with assistance, standing alone and walking alone. A yes response indicates that the patient reached a particular development milestone.
Change From Baseline in Revised Upper Limb Module (RULM), as Appropriate According to Participant Age.	Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52	The RULM assesses motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. 'The scale consists of an entry item to establish functional levels and 19 items covering distal to proximal movements. The entry item is a modified version of the Brooke scale, including activities ranging from no functional use of hands (score 0) to full bilateral shoulder abduction (score 6). The entry item does not contribute to the total score but serves as a functional classification of overall upper limb functional ability. Of the remaining 19 items, 18 are scored on a 3 point scoring system and 1 item is scored on a 2 point scoring system. The test is performed unilaterally using the limb preferred by the participant. The total score ranges from 0, if all the items cannot be performed, to 37, if all the activities are achieved fully without any compensation. ' Higher scores indicate higher levels of motor ability.
Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE), as Appropriate According to Participant Age	Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52	The HFMSE was devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE is formed of 33 assessments. Each motor skill item is scored on a 3 point Likert scale from 0 (no response) to 2 (full response), with a total score range of 0 to 66. A higher score indicates a higher level of ability.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 Newcastle Upon Tyne, United Kingdom