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 (STRENGTH)
Primary Purpose
Spinal Muscular Atrophy
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
OAV101
Sponsored by
About this trial
This is an interventional treatment trial for Spinal Muscular Atrophy focused on measuring 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
Eligibility Criteria
Inclusion Criteria
- SMA diagnosis
- Aged 2 to 12 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
- Requiring invasive ventilation
Sites / Locations
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
OAV-101
Arm Description
Intrathecal administration of OAV101 at a dose of 1.2 x 10^14 vector genomes, one time dose
Outcomes
Primary Outcome Measures
Number and percentage of participants reporting AEs, related AEs, SAEs, and AESIs
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 AESI is primarily defined by using standard Medical Dictionary for Regulatory Activities (MedDRA) queries, and identified as follows: Hepatotoxicity, Thrombocytopenia, Thrombotic microangiopathy, Cardiac adverse events, and Dorsal root ganglia toxicity
Secondary Outcome Measures
Change from baseline to Week 52 visit in the HFMSE total score
The Hammersmith Functional Motor Scale Expanded (HFMSE) is a SMA-specific 33-item assessment that is administered by clinical evaluators in a short period of time, requires minimal equipment, and is designed to factor in patient fatigue. 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 to Week 52 visit in the RULM total Score
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 to Week 52 visit in Assessment of Caregiver Experience in ACEND instrument score
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 a greater impact on the caregiver.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05386680
Brief Title
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
Acronym
STRENGTH
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 12, 2023 (Actual)
Primary Completion Date
October 21, 2024 (Anticipated)
Study Completion Date
December 6, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an open-label, single arm, multi-center study. Approximately 28 participants aged 2 to <18 years will be enrolled stratified as 2 to 5 years and 6 to < 18 years. The study is comprised of 3 periods, Screening (up to 45 days), Treatment (1 day), and Follow-up (52 weeks).
Detailed Description
During the Screening period and on Day -1 (Baseline), eligibility will be assessed, including confirmation that nusinersen (Spinraza®) or risdiplam (Evrysdi®) have not been used for the defined period (4 month and 15 days prior to Day -1 respectively). On Day - 1 (Baseline) participants will be admitted to the hospital for pre-treatment baseline procedures. Prednisolone (or equivalent) will be given and continued as per the study protocol.
Participants who meet eligibility criteria at Screening and Baseline will receive a single dose of OAV101 (1.2 x 10^14 vector genomes) by lumbar intrathecal injection on Day 1 (Treatment) and will then undergo in-patient safety monitoring atleast the next 48 hours, after which the participant may be discharged according to Investigator judgement.
During Follow-up, safety monitoring will continue as per the visits defined in the Assessment Schedule. Safety for participants enrolled will be evaluated by the study team together with the Data Monitoring Committee (DMC).
Final analysis will be performed after all participants have completed Week 52 or discontinued prior to Week 52. At the end of study, participants will be invited to enroll in a Novartis-sponsored long-term follow-up study to monitor long-term safety and efficacy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
28 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
OAV-101
Arm Type
Experimental
Arm Description
Intrathecal administration of OAV101 at a dose of 1.2 x 10^14 vector genomes, one time dose
Intervention Type
Genetic
Intervention Name(s)
OAV101
Other Intervention Name(s)
AVXS-101, Zolgensma
Intervention Description
Intrathecal administration of OAV101 at a dose of 1.2 x 10^14 vector genomes, one time dose
Primary Outcome Measure Information:
Title
Number and percentage of participants reporting AEs, related AEs, SAEs, and AESIs
Description
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 AESI is primarily defined by using standard Medical Dictionary for Regulatory Activities (MedDRA) queries, and identified as follows: Hepatotoxicity, Thrombocytopenia, Thrombotic microangiopathy, Cardiac adverse events, and Dorsal root ganglia toxicity
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Change from baseline to Week 52 visit in the HFMSE total score
Description
The Hammersmith Functional Motor Scale Expanded (HFMSE) is a SMA-specific 33-item assessment that is administered by clinical evaluators in a short period of time, requires minimal equipment, and is designed to factor in patient fatigue. 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.
Time Frame
52 weeks
Title
Change from baseline to Week 52 visit in the RULM total Score
Description
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.
Time Frame
52 weeks
Title
Change from baseline to Week 52 visit in Assessment of Caregiver Experience in ACEND instrument score
Description
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 a greater impact on the caregiver.
Time Frame
52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
1-888-669-6682
Email
medinfo.gtx@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Email
medinfoemea.gtx@novartis.com
Facility Information:
Facility Name
Novartis Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792-7375
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Bron Cedex
ZIP/Postal Code
69677
Country
France
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Toulouse Cedex
ZIP/Postal Code
31059
Country
France
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00168
Country
Italy
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kurume city
State/Province
Fukuoka
ZIP/Postal Code
830-0011
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Shinjuku ku
State/Province
Tokyo
ZIP/Postal Code
162 8666
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Utrecht
ZIP/Postal Code
3584CX
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.
IPD Sharing URL
https://www.clinicalstudydatarequest.com/
Learn more about this trial
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
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