Safety and efficacy of Intrathecal OAV101 in Pediatric Patients with Spinal Muscular Atrophy (SMA) (STEER)

• Register: EUCTR
• Last refreshed on: 19 February 2024
• Main ID: EUCTR2021-003474-31-GR
• Date of registration: 15/09/2022
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma AG
• Public title: Safety and efficacy of Intrathecal OAV101 in Pediatric Patients with Spinal Muscular Atrophy (SMA) (STEER)
• Scientific title: A randomized, sham-controlled, double-blind study to evaluate the efficacy and safety of intrathecal (IT) OAV101 in patients with later onset Type 2 spinal muscular atrophy (SMA) who are = 2 to < 18 years of age, treatment naive, sitting, and never ambulatory - STEER
• Date of first enrolment: 03/01/2023
• Target sample size: 125
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-003474-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Sham-procedure Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Brazil, China, Colombia, Denmark, Egypt, Greece, India, Italy, Malaysia, Mexico, Russian Federation, Saudi Arabia, Singapore, South Africa, Taiwan, Thailand, United Arab Emirates, United States, Viet Nam

Contacts

• Name: Medical information Desk
• Affiliation: Novartis (Hellas) S.A.C.I.

• Name: Medical information Desk
• Affiliation: Novartis (Hellas) S.A.C.I.

Key inclusion & exclusion criteria

Inclusion criteria:
- Diagnostic confirmation during screening period of 5q SMA
- The patient must be treatment naive (historical or current use) for all SMN-targeting therapies (e.g., risdiplam (Evrysdi) and nusinersen (Spinraza)).
- = 2 years and < 18 years of age at screening visit 1
- Onset of clinical signs and symptoms at = 6 months of age
- Patient must have a complete HFMSE assessment with an available total score, as administered by qualified clinical evaluator during the screening period for trial eligibility
- Able to sit independently at screening, but has never had the ability to walk independently.
- Estimated life expectancy > 2 years from screening, in the opinion of the Investigator
- Meets age-appropriate institutional criteria for use of anesthesia/sedation as assessed by the physician responsible for administering anesthesia/sedation

(Full list of inclusion criteria can be found in the clinical protocol Section 5.1)
Are the trial subjects under 18? yes
Number of subjects for this age range: 125
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Excluding SMA, any medical condition considered clinically significant by the Investigator, including cardiomyopathy, hepatic dysfunction, kidney disorder, endocrine disorder including diabetes
mellitus, gastrointestinal disorders, metabolic disorders, untreated B6 deficiency, severe respiratory compromise and significant brain abnormalities at either Screening or Baseline that, in the opinion of the investigator, would interfere with the overall interpretation of safety or efficacy of the study.
- Anti-AAV9 antibody titers >1:50 at Screening as determined by ligand binding immunoassay. NOTE: A negative anti-AAV9 antibody titer is defined as =1:50.
- Clinically significant abnormalities in test results during screening period and/or during baseline period as determined by the Investigator
- Participants will be excluded from the trial for inpatient surgery hospitalization, hospitalization for a pulmonary event, or hospitalization for nutritional support within 2 months prior to Screening and up to Day 1. In addition, patients will not be eligible for the trial if at Screening, inpatient major surgery is planned at any time during the 64-week study. Any other surgeries must not interfere with the ability of the patient to perform the study assessments.
- Prior injury (e.g., upper or lower limb fracture) or surgical procedure which impacts the participant's ability to perform any of the outcome measure testing required in the protocol and from which the participant has not fully recovered or achieved a stable baseline upon entry into screening period
- Contraindications for lumbar puncture procedure, (including but not limited to cutaneous infection at the treatment site and signs or symptoms of increased intracranial pressure), active administration of any intrathecal therapy, presence of an implanted shunt for the drainage of CSF, presence of an implanted central nervous system (CNS) catheter, or any impediment to CSF access.

(Full list of exclusion criteria can be found in the clinical protocol Section
5.2)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Spinal Muscular Atrophy
MedDRA version: 20.1 Level: PT Classification code 10041582 Term: Spinal muscular atrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Trade Name: Zolgensma
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Onasemnogene abeparvovec
CAS Number: 1922968-73-7
Current Sponsor code: OAV101
Other descriptive name: previously termed sc.AAV9.CB.SMN and AVXS-101
Concentration unit: vector genomes (vg)/mL
Concentration type: equal
Concentration number: 40000000000000-

Trade Name: Okrido 6mg/mL oral solution
Product Name: Okrido
Pharmaceutical Form: Oral solution
INN or Proposed INN: PREDNISOLONE SODIUM PHOSPHATE
CAS Number: 125-02-0
Current Sponsor code: prednisolone
Other descriptive name: PREDNISOLONE SODIUM PHOSPHATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: up to 12 months

Secondary Objective: - To compare the efficacy of OAV101 IT vs. sham control in two patient age groups: = 2 to < 5 years (HFMSE, Revised Upper Limb Module (RULM)); = 2 to < 18 years (RULM)
- To evaluate the safety and tolerability of OAV101 IT vs. sham control in patients = 2 to < 18 years)

Main Objective: To compare the efficacy of OAV101 IT vs. sham control as measured by the change from baseline in Hammersmith Functional Motor Scale- Expanded (HFMSE) total score.

Primary end point(s): Change from baseline in HFMSE total score at the end of Follow-up Period 1 (defined in Section 12.4.1 of the clinical protocol) in the overall study population (= 2 to < 18 years age group)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Up to 12 months

Secondary end point(s): - Change from baseline in HFMSE total score at the end of Follow-up Period 1 in the = 2 to < 5 years age group
- Achievement of at least a 3-point improvement from baseline in HFMSE total score at the end of Follow-up Period 1 in the overall study population
- Achievement of at least a 3-point improvement from baseline in HFMSE total score at the end of Follow-up Period 1 in the = 2 to < 5 years age group
- Change from baseline in RULM at the end of Follow-up Period 1 in the = 2 to < 18 years age group
- Change from baseline in the RULM at the end of Follow-up Period 1 in the = 2 to < 5 years age group
- Incidence of treatment emergent adverse events (TEAEs) and serious TEAEs (SAEs)
- Number of participants with adverse events of special interest (AESIs)
- Evaluation of changes from baseline in vital signs, physical/neurological examinations, laboratories (chemistry, hematology, liver function tests), echocardiogram, ECG, anthropometry, and C-SSRS
- Number (and percentage) of patients with intracardiac thrombi
- Number(and percentage) of patients with low cardiac function
- Evaluation of vector shedding in treated patients.

Secondary ID(s)

2021-003474-31-DK

COAV101B12301

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date: 15/12/2022
Contact: