Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials

Spinal Muscular Atrophy (SMA) Clinical Trial

— SPECTRUM  

Official title:

Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 IT or OAV101 IV in Clinical Trials

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05335876
• Other study ID #: COAV101A12308
• Status: Recruiting
• Phase: Phase 3
• Start date: December 19, 2022
• Est. completion date: October 18, 2039

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: Novartis Gene Therapies Med Info (US, Latin America, Canada)
• Phone: +1-833-828-3947
• Email: medinfo.gtx[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a global, prospective, multi-center study that is designed to assess the long-term safety and efficacy of OAV101 in patients who participated in an OAV101 clinical trial. The assessments of safety and efficacy in Study COAV101A12308 will continue for 15 years from the date of OAV101 administration in the previous clinical trial.

Description:

The study is comprised of a Baseline Period and 3 Follow-up Periods. Follow-up Periods 1 and 2 consist of in-person visits and Period 3 consists of tele-visits. Follow-up Periods 1 and 2, which includes Baseline through Year 5 visits, assessments will be performed at the Investigational site. During Follow-up Period 3 (Year 6 to up to Year 15 after OAV101 administration), participants/caregivers will be contacted using tele-visits annually for remote assessments. All patients will enter the study at the baseline visit and continue until 15 years since OAV101 administration is reached. Total duration of participation in the study will be dependent upon time of enrollment relative to OAV101 administration and will vary by participant.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: October 18, 2039
• Est. primary completion date: October 18, 2039
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. Participated in an OAV101 clinical trial.

2. Written informed consent must be obtained before any assessment is performed.

3. Patient/Parent/legal guardian willing and able to comply with study procedures.

Exclusion Criteria:

There are no exclusion criteria for this study.

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy (SMA)

Intervention

Biological:
• onasemnogene abeparvovec
Onasemnogene abeparvovec is a non-replicating recombinant adeno-associated virus serotype 9 containing the human survival motor neuron gene under the control of the ytomegalovirus enhancer/chicken ß-actin-hybrid promoter. Onasemnogene abeparvovec is administered as a one-time intravenous (IV) infusion or intrathecal (IT) injection. Dosage determined by participant weight.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Randwick	New South Wales
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Montreal	Quebec
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Chengdu	Sichuan
Denmark	Novartis Investigative Site	Copenhagen
France	Novartis Investigative Site	Garches
France	Novartis Investigative Site	Strasbourg
Italy	Novartis Investigative Site	Roma	RM
Japan	Novartis Investigative Site	Kurume city	Fukuoka
Japan	Novartis Investigative Site	Shinjuku ku	Tokyo
Malaysia	Novartis Investigative Site	Kuala Lumpur
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Taipei
Thailand	Novartis Investigative Site	Bangkok
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Newcastle Upon Tyne
United States	Child Hosp of the Kings Daughters	Norfolk	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  China,  Denmark,  France,  Italy,  Japan,  Malaysia,  Singapore,  Spain,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-emergent serious adverse events (SAEs)	An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing)] undesirable sign(s), symptom(s), or medical conditions(s) which meets any one of the following criteria: fatal; life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect, fetal death or congenital abnormality or birth defect; requires in-patient hospitalization or prolongation of existing hospitalization, unless hospitalization is for routine treatment or monitoring of the studied indication, not associated with any deterioration in condition; is medically significant, e.g. defined as an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above	Up to Year 15
Primary	Number of participants with treatment emergent Adverse Events of Special Interest (AESI)	The following are important identified and important potential risks (AESI) associated with OAV101: Hepatotoxicity, Transient Thrombocytopenia, Cardiac adverse events, Sensory abnormalities suggestive of ganglionopathy, and Thrombotic microangiopathy. These will be assessed by the investigator.	Up to Year 15
Secondary	The number of participants demonstrating each developmental milestone according to the Developmental Milestone Checklist	The Developmental Milestone Checklist is a sponsor created list of items using relevant definitions obtained from World Health Organization Multicentre Growth Reference Study (WHO-MGRS). These will be assessed via the milestone checklist, formed of 6 yes/no questions. The developmental milestones are: sitting with support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone and walking alone. A yes response indicates that the patient reached a particular development milestone.	Up to Year 5
Secondary	The number of participants demonstrating maintenance of each developmental milestone according to the Developmental Milestone Checklist	The Developmental Milestone Checklist is a sponsor created list of items using relevant definitions obtained from World Health Organization Multicentre Growth Reference Study (WHO-MGRS). These will be assessed via the milestone checklist, formed of 6 yes/no questions. The developmental milestones are: sitting with support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone and walking alone. A yes response indicates that the patient reached a particular development milestone.	Up to Year 5
Secondary	Change from Baseline in the Hammersmith Functional Motor Scale - Expanded (HFMSE) total score	The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.	Up to Year 5
Secondary	Change from Baseline in the Revised Upper Limb Module (RULM) total score	The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. The scale consists of 19 scorable items: 18 items scored on 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). Total scores range from 0-37 points. Higher scores reflect higher level of motor ability.	Up to Year 5
Secondary	Systolic and diastolic blood pressure (mmHg)		Up to Year 15
Secondary	Number of patients with potentialy clinically significant vital sign findings - Respiratory Rate (breaths/min)		Up to Year 15
Secondary	Number of patients with potentialy clinically significant vital sign findings -Pulse Rate (beats/min)		Up to Year 15
Secondary	Number of patients with potentialy clinically significant vital sign findings -Temperature (Degrees Celsius)		Up to Year 15
Secondary	Number of patients with potentialy clinically significant vital sign findings -Oxygen saturation level (%).	Oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated+saturated) in the blood and then multiplied by 100.	Up to Year 15