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 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®)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05386680

Acronym

STRENGTH

Enrollment

Registered

2022-05-23

Start date

2023-01-12

Completion date

2024-11-29

Last updated

2026-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

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

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.

Interventions

GENETICOAV101

Intrathecal administration of OAV101 at a dose of 1.2 x 10\^14 vector genomes, one time dose

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

2 Years to 17 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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 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 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.
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 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.

Countries

Australia, Belgium, Canada, France, Italy, Japan, Netherlands, Spain, United States

Participant flow

Participants by arm

Arm	Count
OAV101 1.2x1014 vg - All Participants Intrathecal administration of OAV101 at a dose of 1.2 x 10\^14 vector genomes, one time dose	27
Total	27

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Guardian decision	2

Baseline characteristics

Characteristic	OAV101 1.2x1014 vg - All Participants
Age, Continuous	7.40 years STANDARD_DEVIATION 3.348
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	6 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants
Race (NIH/OMB) White	13 Participants
Sex: Female, Male Female	12 Participants
Sex: Female, Male Male	15 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 27
other Total, other adverse events	27 / 27
serious Total, serious adverse events	4 / 27

Outcome results

Primary

Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup

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.

Time frame: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.

Population: Full analysis set - all treated participants

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	Hepatotoxicity - Number of participants with at least one event	4 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	-Hepatic enzyme increased	3 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	-Hypertransaminasaemia	1 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	Transient thrombocytopenia - Number of participants with at least one event	8 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	-Epistaxis	3 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	-Contusion	2 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	-Bone contusion	1 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	-Gastric haemorrhage	1 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	-Lower gastrointestinal haemorrhage	1 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	-Petechiae	1 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	Signs of dorsal root ganglia toxicity - No. of pts. with at least one event	2 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	-Paraesthesia	1 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	-Sensory disturbance	1 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	Thrombotic microangiopathy - Number of participants with at least one event	0 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	Cardiac adverse events - Number of participants with at least one event	0 Participants
OAV101 1.2x1014 vg - All Participants	Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup	New malignancies - Number of participants with at least one event	0 Participants

Primary

Overview of Treatment-emergent Adverse Events by Age Subgroup

Time frame: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.

Population: Full analysis set - all treated participants

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
OAV101 1.2x1014 vg - All Participants	Overview of Treatment-emergent Adverse Events by Age Subgroup	Any treatment-emergent adverse event	27 Participants
OAV101 1.2x1014 vg - All Participants	Overview of Treatment-emergent Adverse Events by Age Subgroup	Any treatment-emergent adverse event related to study treatment	13 Participants
OAV101 1.2x1014 vg - All Participants	Overview of Treatment-emergent Adverse Events by Age Subgroup	Any serious treatment-emergent adverse event	4 Participants
OAV101 1.2x1014 vg - All Participants	Overview of Treatment-emergent Adverse Events by Age Subgroup	Any serious treatment-emergent adverse event related to study treatment	0 Participants
OAV101 1.2x1014 vg - All Participants	Overview of Treatment-emergent Adverse Events by Age Subgroup	Any severe treatment-emergent adverse event	1 Participants
OAV101 1.2x1014 vg - All Participants	Overview of Treatment-emergent Adverse Events by Age Subgroup	Any treatment-emergent adverse event leading to study discontinuation	0 Participants
OAV101 1.2x1014 vg - All Participants	Overview of Treatment-emergent Adverse Events by Age Subgroup	Any treatment-emergent adverse event leading to death	0 Participants
OAV101 1.2x1014 vg - All Participants	Overview of Treatment-emergent Adverse Events by Age Subgroup	Any treatment-emergent adverse event of special interest	13 Participants

Primary

Treatment-emergent Adverse Events Related to Treatment by System Organ Class, Preferred Term, Age Subgroup (>= 10%)

Time frame: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.

Population: Full analysis set - all treated participants

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
OAV101 1.2x1014 vg - All Participants	Treatment-emergent Adverse Events Related to Treatment by System Organ Class, Preferred Term, Age Subgroup (>= 10%)	Number of participants with at least one event	13 Participants
OAV101 1.2x1014 vg - All Participants	Treatment-emergent Adverse Events Related to Treatment by System Organ Class, Preferred Term, Age Subgroup (>= 10%)	Gastrointestinal disorders	7 Participants
OAV101 1.2x1014 vg - All Participants	Treatment-emergent Adverse Events Related to Treatment by System Organ Class, Preferred Term, Age Subgroup (>= 10%)	-Vomiting	6 Participants
OAV101 1.2x1014 vg - All Participants	Treatment-emergent Adverse Events Related to Treatment by System Organ Class, Preferred Term, Age Subgroup (>= 10%)	General disorders and administration site conditions	5 Participants
OAV101 1.2x1014 vg - All Participants	Treatment-emergent Adverse Events Related to Treatment by System Organ Class, Preferred Term, Age Subgroup (>= 10%)	-Pyrexia	3 Participants
OAV101 1.2x1014 vg - All Participants	Treatment-emergent Adverse Events Related to Treatment by System Organ Class, Preferred Term, Age Subgroup (>= 10%)	Nervous system disorders	6 Participants
OAV101 1.2x1014 vg - All Participants	Treatment-emergent Adverse Events Related to Treatment by System Organ Class, Preferred Term, Age Subgroup (>= 10%)	-Headache	4 Participants

Secondary

Change From Baseline at Week 52 Visit in Assessment of Caregiver Experience in ACEND Instrument Score - LS Means

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.

Time frame: Baseline, Week 52