Long-term Follow-up Study of Patients Receiving Onasemnogene Abeparvovec-xioi

SMA Clinical Trial

Official title:

A Long-term Follow-up Study of Patients in the Clinical Trials for Spinal Muscular Atrophy Receiving AVXS-101

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04042025
• Other study ID #: AVXS-101-LT-002
• Secondary ID: 2019-002611-2620
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 10, 2020
• Est. completion date: December 31, 2035

Study information

• Verified date: February 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a long-term follow-up safety and efficacy study of participants in clinical trials for spinal muscular atrophy (SMA) who were treated with onasemnogene abeparvovec-xioi. Participants will roll over from their respective previous (parent) study into this long-term study for continuous monitoring of safety as well as monitoring of continued efficacy and durability of response to onasemnogene abeparvovec-xioi treatment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 85
• Est. completion date: December 31, 2035
• Est. primary completion date: December 31, 2035
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Any participant with SMA who received onasemnogene abeparvovec-xioi gene replacement therapy in a Novartis Gene Therapies-sponsored clinical study
• Participant/parent/legal guardian willing and able to complete the informed consent process and comply with study procedures and visit schedule

Exclusion Criteria:

• Parent/legal guardian unable or unwilling to participate in the long-term follow-up safety study

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• SMA
• Spinal Muscular Atrophy Type I
• Spinal Muscular Atrophy Type II
• Spinal Muscular Atrophy Type III

Intervention

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

Locations

Country	Name	City	State
Australia	Sydney Children's Hospital	Randwick	New South Wales
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Centre de Référence des Maladies Neuromusculaires	Liège
Canada	Children's Hospital of Eastern Ontario Research Institute	Ottawa	Ontario
France	Hôpital Armand Trousseau	Paris
Italy	Instituto Gianninia Gaslini	Genova
Italy	Istituto Neurologico di Ricerca	Milan
Italy	Universita Degli Studi Di Milano	Milan
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Japan	Tokyo Women's Medical University Hospital	Tokyo
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Great Ormond Street Hospital for Children NHS Foundation Trust	London
United Kingdom	The Newcastle Upon Tyne Hospitals NHS Foundation Trust	Newcastle Upon Tyne
United States	Children's Hospital Colorado	Aurora	Colorado
United States	John Hopkins Hospital - David M. Rubenstein Child Health Building	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Ann Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Health Specialty Center Dallas Campus	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Spectrum Health Hospitals Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	University of Wisconsin, Madison	Madison	Wisconsin
United States	Columbia University Medical Center	New York	New York
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	Stanford University Medical Center	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington Unviersity School of Medicine in Saint Louis	Saint Louis	Missouri
United States	University of Utah Health	Salt Lake City	Utah
United States	Clinic for Special Children	Strasburg	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Gene Therapies

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Italy,  Japan,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Reach Developmental Milestones	Assessed via the developmental milestone checklist, formed of 10 yes/no questions. The developmental milestones are: head control, sitting with support, sitting without support, sitting without support for 30 seconds, hands-and-knees crawling, pulls to stand, standing with assistance, walking with assistance, standing alone and walking alone.	Up to 5 years
Primary	Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score	The HFMSE was devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE is formed of 33 assessments rated from 0 (unable to perform functional task) to 2 (able to perform functional task unassisted). Higher scores on the total scale of 0-66 indicates higher levels of motor ability.	Up to 5 years
Primary	Number of Participants Who Experience a Clinically Significant Change From Baseline in Pulmonary Assessment Results and Require Ventilatory Support	Participants will receive pulmonary assessments by a pulmonologist or appropriate clinician. Respiratory device data will be reviewed for participants receiving non-invasive ventilatory support.	Up to 15 years
Primary	Number of Participants Who Experience Swallowing Dysfunction and Require Nutritional Support	Assessed via the swallowing function questionnaire, formed of 4 yes/ no questions and 1 body weight question.	Up to 5 years
Primary	Number of Participants Who Experience a Clinically Significant Change from Baseline in Physical Examination Findings	The physical examination includes review of the following systems: head, ears, eyes, nose and throat, lungs/thorax, cardiovascular, abdomen, musculoskeletal, neurologic, dermatologic, lymphatic, and genitourinary. In addition, visual inspection of the spine, back, shoulders, and hips looking for spinal curvature and asymmetry will be carried out. Joints will be assessed for loss of mobility and contractures.	Up to 5 years
Primary	Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Signs Measurements	Vital sign measurements will include blood pressure, respiratory rate, pulse, axillary temperature, and pulse oximetry.	Up to 5 years
Primary	Change From Baseline in Height Measurements		Up to 5 years
Primary	Change From Baseline in Weight Measurements		Up to 5 years
Primary	Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Assessments	Blood samples will be collected for hematology (including complete blood cell count) and chemistry.	Up to 5 years
Primary	Number of Participants Who Experience a Clinically Significant Change From Baseline in Cardiac Assessments	Cardiac assessments will include a 12-lead electrocardiogram, transthoracic echocardiogram and Troponin-I.	Up to 5 years
Primary	Number of Participants Who Experience a Clinically Significant Change From Baseline in Observational Phase Questionnaire Results	The observational phase questionnaire includes 7 yes/no questions. Observation categories include: adverse events, hospitalizations, concomitant medications, ventilatory support and feeding support.	Year 6 to Year 15
Primary	Number of Participants Who Experience at Least One Serious Adverse Event (SAE)	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 abnormality or birth defect; Requires in-patient hospitalization or prolongation of existing hospitalization; 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 15 years
Primary	Number of Participants Who Experience at Least One Adverse Event of Special Interest (AESI)	An AESI is defined as an AE occurring during any study phase that fulfills one of the following criteria: Hepatotoxicity; Thrombotic microangiopathy; Cardiac adverse events; Dorsal root ganglia toxicity; New malignancies; New incidence of a neurologic disorder; New incidence of an autoimmune disorder; New incidence of hematologic disorder	Up to 15 years
Primary	Change From Baseline in Bayley Scales of Infant and Toddler Development	Third Edition (Bayley-III) to be performed in all patients up to 42 months, 15 days of age.	Up to 42 months, 15 days of age
Primary	Change From Baseline in Revised Upper Limb Module (RULM) Score	RULM score is based on a scale from 0 to 37 where lower scores reflect poorer upper limb functional ability.	Up to 5 years
Primary	Change From Baseline in Cogstate Computerized Cognitive Battery Performed in Age 48 Months and Older	The Cogstate Computerized Cognitive Battery consists of the Identification Test (scored 0 (best) to 1.5708 (worst)), the International Shopping List Test (scored 0 (worst) to 999 (best)), the International Shopping List Test-Delayed Recall (scored 0 (worst) to 999 (best)), the One Card Learning Test (scored 0 (worst) to 1.5708 (best)), and the One Back Test (scored 0 (worst) to 1.5708 (best)).	Up to 5 years
Primary	Change From Baseline in Clinical Evaluation of Language Fundamentals Fifth Edition (CELF-5) Performed in All Participants 5 to 21 Years of Age	The CELF-5 Following Directions and Sentence Repetition subtests use scoring that varies based on age, but will be administered to participants 5-21 years of age. The Following Directions subtest will be scored from 0-33 with higher score being more advanced and the Recalling Sentences subtest will be scored from 0-78 with higher score being more advanced.	Up to 5 years
Primary	Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND)	ACEND score is based on a scale from 1 to 41 where higher scores represent a better caregiver experience	Up to 5 years
Primary	Number of Participants With Concomitant Medications Overall and by Type of Medications		Up to 5 years
Primary	Number of Participants With Other SMA Therapies Overall and by Type of Medications		Year 6 to Year 15