Clinical trial NCT05386680: Phase IIIb, Open-label, Multi-center Study to Evaluate Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally to Participants With SMA Who Discontinued Treatment With Nusinersen or Risdiplam
Official title: Phase IIIb, Open-label, Single-arm, Multi-center Study to Evaluate the Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally (1.2 x 10^14 Vector Genomes) to Participants 2 to < 18 Years of Age With Spinal Muscular Atrophy (SMA) Who Have Discontinued Treatment With Nusinersen (Spinraza®) or Risdiplam (Evrysdi®)
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
SMA
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-05-23
Enrollment: 27
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was a Phase IIIb open-label, single arm, multi-center study to evaluate the safety, tolerability and efficacy of OAV101B in participants with SMA aged 2 to \<18 years after the discontinuation of treatment with nusinersen or risdiplam. The study aimed to enroll approximately 28 participants across each of 2 age brackets (2 to \<6 years, and 6 to \<18 years).

Detailed description: Eligible participants received a single OAV101B administration of 1.2x1014 vector genomes on Day 1 (Treatment period) and were followed for a period of 52 weeks.

Participants were admitted to the hospital on Day -1 for pre-treatment baseline procedures. After receiving OAV101B 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.

Eligibility criteria: Inclusion Criteria

* SMA diagnosis
* Aged 2 to \< 18 years
* Have had at least four loading doses of nusinersen (Spinraza®) or at least 3 months of treatment with risdiplam (Evrysdi®) at Screening
* Must have symptoms of SMA as defined in the protocol

Exclusion Criteria:

* Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer using an immunoassay is reported as elevated
* Clinically significant abnormalities in test results during screening
* Contraindications for lumbar puncture procedure
* At Baseline, participants are excluded if they received:

  * nusinersen (Spinraza®) or
  * risdiplam (Evrysdi®) within a defined timeframe
* Vaccinations 2 weeks prior to administration of OAV101
* Hospitalization for a pulmonary event, or for nutritional support within 2 months prior to Screening or inpatient major surgery planned.
* Presence of an infection or febrile illness up to 30 days prior to administration of OAV101
* Requiring invasive ventilation

Primary outcomes:
measure: Overview of Treatment-emergent Adverse Events by Age Subgroup
timeFrame: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.
measure: Treatment-emergent Adverse Events Related to Treatment by System Organ Class, Preferred Term, Age Subgroup (>= 10%)
timeFrame: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.
measure: Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup
timeFrame: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.
Secondary outcomes:
measure: Change From Baseline at Week 52 Visit in the HFMSE Total Score - Mean (SD)
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 52 Visit in the HFMSE Total Score - LS Means
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 52 Visit in the RULM Total Score - Mean (SD)
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 52 Visit in the RULM Total Score - LS Means
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 52 Visit in Assessment of Caregiver Experience in ACEND Instrument Score - Mean (SD)
timeFrame: Baseline, Week 52
measure: Change From Baseline at Week 52 Visit in Assessment of Caregiver Experience in ACEND Instrument Score - LS Means
timeFrame: Baseline, Week 52
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Childrens Hospital
state: Massachusetts
city: Norfolk
country: United States
facility: Child Hosp Of The Kings Daughters
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Madison Medical School
state: Wisconsin
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Bron Cedex
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex
country: France
facility: Novartis Investigative Site
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Kurume city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Shinjuku ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
Study officials:
References: