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

Phase 3

Completed

Conditions: Spinal Muscular Atrophy

Registration Number: NCT05386680

Lead Sponsor: Novartis Pharmaceuticals

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 27

Inclusion Criteria

Not provided

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Overview of Treatment-emergent Adverse Events by Age Subgroup	Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.	An adverse event (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. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments.
Treatment-emergent Adverse Events Related to Treatment by System Organ Class, Preferred Term, Age Subgroup (>= 10%)	Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.	An adverse event (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. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments.
Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.	An adverse event (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. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments. An adverse event of special interest (AESI) is primarily defined by using standard Medical Dictionary for Regulatory Activities (MedDRA) queries, and identified as follows: Hepatotoxicity, Transient thrombocytopenia, Thrombotic microangiopathy, Cardiac adverse events, signs and symptoms that may be suggestive dorsal root ganglia toxicity, and new malignancies.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline at Week 52 Visit in the HFMSE Total Score - Mean (SD)	Baseline, Week 52	The Hammersmith Functional Motor Scale Expanded (HFMSE) is a SMA-specific 33-item assessment that is administered by qualified clinical evaluators. 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 ability level.
Change From Baseline at Week 52 Visit in the HFMSE Total Score - LS Means	Baseline, Week 52	The Hammersmith Functional Motor Scale Expanded (HFMSE) is a SMA-specific 33-item assessment that is administered by qualified clinical evaluators. 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 ability level.
Change From Baseline at Week 52 Visit in the RULM Total Score - Mean (SD)	Baseline, Week 52	The Revised Upper Limb Model (RULM) is a validated, SMA-specific assessment that measures motor performance in the upper limbs from childhood through adulthood in ambulatory and never ambulatory individuals with SMA. The revised version of the test consists of 19 scorable items: 18 items scored on a 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). These item scores are summed to give a total score ranging from 0 to 37 points with lower scores reflecting poorer ability.
Change From Baseline at Week 52 Visit in the RULM Total Score - LS Means	Baseline, Week 52	The Revised Upper Limb Model (RULM) is a validated, SMA-specific assessment that measures motor performance in the upper limbs from childhood through adulthood in ambulatory and never ambulatory individuals with SMA. The revised version of the test consists of 19 scorable items: 18 items scored on a 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). These item scores are summed to give a total score ranging from 0 to 37 points with lower scores reflecting poorer ability.
Change From Baseline at Week 52 Visit in Assessment of Caregiver Experience in ACEND Instrument Score - Mean (SD)	Baseline, Week 52	The Assessment of Caregiver Experience in Neuromuscular Disease (ACEND) instrument quantifies the caregiver impact experienced by parents/caregivers of children affected with severe neuromuscular diseases, including children with SMA. The total score is on a scale of 0 to 100 with a higher score indicating that caregivers experienced less intense caregiving impact.
Change From Baseline at Week 52 Visit in Assessment of Caregiver Experience in ACEND Instrument Score - LS Means	Baseline, Week 52	The Assessment of Caregiver Experience in Neuromuscular Disease (ACEND) instrument quantifies the caregiver impact experienced by parents/caregivers of children affected with severe neuromuscular diseases, including children with SMA. The total score is on a scale of 0 to 100 with a higher score indicating that caregivers experienced less intense caregiving impact.

Trial Locations

Locations (4): Boston Childrens Hospital
🇺🇸
Boston, Massachusetts, United States
Child Hosp Of The Kings Daughters
🇺🇸
Norfolk, Virginia, United States
University of Wisconsin Madison Medical School
🇺🇸
Madison, Wisconsin, United States
Novartis Investigative Site
🇪🇸
Barcelona, Catalunya, Spain
Boston Childrens Hospital
🇺🇸Boston, Massachusetts, United States