Clinical trial NCT04851873: Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)
Official title: A Phase IIIb, Open-label, Single-arm, Single-dose, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of Gene Replacement Therapy With Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Spinal Muscular Atrophy
Keywords: Zolgensma
OAV101
AVXS 101
gene therapy
Muscle atrophy
SBMA
spinal and bulbar muscular atrophy
spinal muscular atrophy
bulbar muscular atrophy
muscle function
myopathy
muscle wasting
atrophied muscle
loss of muscle strength
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-04-21
Enrollment: 24
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Participants will receive a single administration of OAV101
Primary purpose: TREATMENT

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))

Eligibility criteria: Inclusion

* Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic survival motor neuron 1 (SMN1) mutations (deletion or point mutations) and any copy of the survival motor neuron 2 (SMN2) gene.
* Weight ≥ 8.5 kg and ≤ 21 kg at the time of Screening Visit 2
* Naive to treatment or have discontinued an approved drug/therapy

Exclusion:

* Previous OAV101 use or previous use of any adeno-associated virus serotype 9 (AAV9) gene therapy
* BMI \< 3rd percentile
* Participant with history of aspiration pneumonia or signs of aspiration
* Elevated anti-AAV9 antibody
* History of gene therapy, hematopoietic transplantation, or solid organ transplantation
* Inability to take corticosteroids
* Concomitant use of immunosuppressive therapy
* Requiring invasive ventilation, tracheostomy or awake non-invasive ventilation 9. Administration of vaccines 2 weeks prior to infusion of OAV101
* Awake hypoxemia or awake oxygen saturation level decrease
* Hepatic dysfunction
* Presence of a confirmed or suspected infection
* If previously treated with disease modifying therapy, specified washout times apply
* Documented any parental consanguinity.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Weight Bracket
timeFrame: Up to Month 12
measure: Number of Participants With Important Identified and Important Potential Risks (Adverse Events of Special Interest (AESI)) by Risk Name and Weight Bracket
timeFrame: Up to Month 12
measure: Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Systolic and Diastolic Blood Pressure
timeFrame: 12 months
measure: Change From Baseline in Vital Signs Measurements - Systolic Blood Pressure (mmHg)
timeFrame: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
measure: Change From Baseline in Vital Signs Measurements - Diastolic Blood Pressure (mmHg)
timeFrame: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
measure: Change From Baseline in Vital Signs Measurements - Respiratory Rate (Breaths/Min)
timeFrame: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
measure: Change From Baseline in Vital Signs Measurements - Pulse Rate (Beats/Min)
timeFrame: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
measure: Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Temperature
timeFrame: 12 months
measure: Change From Baseline in Vital Signs Measurements - Temperature (Degrees Celsius)
timeFrame: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
measure: Change From Baseline in Vital Signs Measurements - Oxygen Saturation Level
timeFrame: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Secondary outcomes:
measure: Achievement of Development Motor Milestones According to the Modified and Combined WHO-MGRS and Bayley Scale of Infant and Toddler Development.
timeFrame: Baseline, Week 26 and Week 52
measure: Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE), as Appropriate According to Participant Age
timeFrame: Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52
measure: Change From Baseline in Revised Upper Limb Module (RULM), as Appropriate According to Participant Age.
timeFrame: Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52
Other outcomes:
Locations:
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Randwick
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Garches
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: