Long-term Follow-up Study of Patients Receiving Onasemnogene Abeparvovec-xioi
- Conditions
- Spinal Muscular Atrophy Type ISpinal Muscular Atrophy Type IISpinal Muscular Atrophy Type IIISMA
- Interventions
- Registration Number
- NCT04042025
- Lead Sponsor
- Novartis Gene Therapies
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 85
- 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
- Parent/legal guardian unable or unwilling to participate in the long-term follow-up safety study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Intravenous (IV) & Intrathecal (IT) Onasemnogene Abeparvovec-xioi Onasemnogene Abeparvovec-xioi Participants received treatment with IV onasemnogene abeparvovec-xioi in an onasemnogene abeparvovec-xioi or received treatment with IT onasemnogene abeparvovec-xioi in an onasemnogene.
- Primary Outcome Measures
Name Time Method Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Assessments Up to 5 years Blood samples will be collected for hematology (including complete blood cell count) and chemistry.
Change From Baseline in Height Measurements Up to 5 years Number of Participants Who Experience a Clinically Significant Change From Baseline in Pulmonary Assessment Results and Require Ventilatory Support Up to 15 years Participants will receive pulmonary assessments by a pulmonologist or appropriate clinician. Respiratory device data will be reviewed for participants receiving non-invasive ventilatory support.
Number of Participants Who Experience a Clinically Significant Change From Baseline in Cardiac Assessments Up to 5 years Cardiac assessments will include a 12-lead electrocardiogram, transthoracic echocardiogram and Troponin-I.
Number of Participants Who Reach Developmental Milestones Up to 5 years 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.
Number of Participants Who Experience Swallowing Dysfunction and Require Nutritional Support Up to 5 years Assessed via the swallowing function questionnaire, formed of 4 yes/ no questions and 1 body weight question.
Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Signs Measurements Up to 5 years Vital sign measurements will include blood pressure, respiratory rate, pulse, axillary temperature, and pulse oximetry.
Change From Baseline in Weight Measurements Up to 5 years Number of Participants Who Experience at Least One Adverse Event of Special Interest (AESI) Up to 15 years 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 disorderChange From Baseline in Bayley Scales of Infant and Toddler Development Up to 42 months, 15 days of age Third Edition (Bayley-III) to be performed in all patients up to 42 months, 15 days of age.
Change From Baseline in Revised Upper Limb Module (RULM) Score Up to 5 years RULM score is based on a scale from 0 to 37 where lower scores reflect poorer upper limb functional ability.
Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) Up to 5 years ACEND score is based on a scale from 1 to 41 where higher scores represent a better caregiver experience
Number of Participants With Other SMA Therapies Overall and by Type of Medications Year 6 to Year 15 Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score Up to 5 years 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.
Number of Participants Who Experience a Clinically Significant Change from Baseline in Physical Examination Findings Up to 5 years 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.
Number of Participants Who Experience a Clinically Significant Change From Baseline in Observational Phase Questionnaire Results Year 6 to Year 15 The observational phase questionnaire includes 7 yes/no questions. Observation categories include: adverse events, hospitalizations, concomitant medications, ventilatory support and feeding support.
Change From Baseline in Clinical Evaluation of Language Fundamentals Fifth Edition (CELF-5) Performed in All Participants 5 to 21 Years of Age Up to 5 years 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.
Number of Participants With Concomitant Medications Overall and by Type of Medications Up to 5 years Number of Participants Who Experience at Least One Serious Adverse Event (SAE) Up to 15 years 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 aboveChange From Baseline in Cogstate Computerized Cognitive Battery Performed in Age 48 Months and Older Up to 5 years 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)).
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (31)
Washington Unviersity School of Medicine in Saint Louis
🇺🇸Saint Louis, Missouri, United States
University of Utah Health
🇺🇸Salt Lake City, Utah, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Great Ormond Street Hospital for Children NHS Foundation Trust
🇬🇧London, United Kingdom
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Children's Hospital of Eastern Ontario Research Institute
🇨🇦Ottawa, Ontario, Canada
Clinic for Special Children
🇺🇸Strasburg, Pennsylvania, United States
University of Wisconsin, Madison
🇺🇸Madison, Wisconsin, United States
Sydney Children's Hospital
🇦🇺Randwick, New South Wales, Australia
Hôpital Armand Trousseau
🇫🇷Paris, France
John Hopkins Hospital - David M. Rubenstein Child Health Building
🇺🇸Baltimore, Maryland, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Ann Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Spectrum Health Hospitals Helen DeVos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Children's Health Specialty Center Dallas Campus
🇺🇸Dallas, Texas, United States
Istituto Neurologico di Ricerca
🇮🇹Milan, Italy
Instituto Gianninia Gaslini
🇮🇹Genova, Italy
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Tokyo Women's Medical University Hospital
🇯🇵Tokyo, Japan
Duke University
🇺🇸Durham, North Carolina, United States
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Centre de Référence des Maladies Neuromusculaires
🇧🇪Liège, Belgium
Universita Degli Studi Di Milano
🇮🇹Milan, Italy
Fondazione Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle Upon Tyne, United Kingdom