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

NCT04042025 | Active Not Recruiting Phase 3 DMC FDA Drug

• 4 other identifiers: AVXS-101-LT-0022019-002611-26205305COAV101A12103
• Study Type: interventional
• Target: 85
• Locations: 9 countries
• Sites: 31

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.

Conditions

Spinal Muscular Atrophy Type I; Spinal Muscular Atrophy Type II; Spinal Muscular Atrophy Type III; SMA

Keywords

Gene replacement

Outcome Measures

Primary Outcomes (20)

• 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

• 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

• 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

• 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

• 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

• 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

• Change From Baseline in Height Measurements

  Up to 5 years

• Change From Baseline in Weight Measurements

  Up to 5 years

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• Number of Participants With Concomitant Medications Overall and by Type of Medications

  Up to 5 years

• Number of Participants With Other SMA Therapies Overall and by Type of Medications

  Year 6 to Year 15

Study Arms (1)

Intravenous (IV) & Intrathecal (IT) Onasemnogene Abeparvovec-xioi

OTHER

Participants received treatment with IV onasemnogene abeparvovec-xioi in an onasemnogene abeparvovec-xioi or received treatment with IT onasemnogene abeparvovec-xioi in an onasemnogene.

Biological: Onasemnogene Abeparvovec-xioi

Interventions

Onasemnogene Abeparvovec-xioi BIOLOGICAL

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 β-actin-hybrid promoter. Onasemnogene abeparvovec-xioi administered as a one-time intravenous (IV) infusion or intrathecal (IT) injection. Dosage determined by participant weight.

Also known as: Zolgensma

Intravenous (IV) & Intrathecal (IT) Onasemnogene Abeparvovec-xioi

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Novartis Gene Therapies: lead

Study Sites (31)

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Ann Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

John Hopkins Hospital - David M. Rubenstein Child Health Building

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Spectrum Health Hospitals Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

Washington Unviersity School of Medicine in Saint Louis

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University

Durham, North Carolina, 27713, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Clinic for Special Children

Strasburg, Pennsylvania, 17579, United States

Location

Children's Health Specialty Center Dallas Campus

Dallas, Texas, 75235, United States

Location

University of Utah Health

Salt Lake City, Utah, 84112, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

University of Wisconsin, Madison

Madison, Wisconsin, 53792, United States

Location

Sydney Children's Hospital

Randwick, New South Wales, 2145, Australia

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Centre de Référence des Maladies Neuromusculaires

Liège, B-4000, Belgium

Location

Children's Hospital of Eastern Ontario Research Institute

Ottawa, Ontario, K1H8L1, Canada

Location

Hôpital Armand Trousseau

Paris, 75012, France

Location

Instituto Gianninia Gaslini

Genova, 16147, Italy

Location

Universita Degli Studi Di Milano

Milan, 20122, Italy

Location

Istituto Neurologico di Ricerca

Milan, 20133, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

Tokyo Women's Medical University Hospital

Tokyo, 162-8666, Japan

Location

National Taiwan University Hospital

Taipei, 10048, Taiwan

Location

Great Ormond Street Hospital for Children NHS Foundation Trust

London, WC1N 3JH, United Kingdom

Location

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (1)

• Day JW, Mendell JR, Mercuri E, Finkel RS, Strauss KA, Kleyn A, Tauscher-Wisniewski S, Tukov FF, Reyna SP, Chand DH. Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy. Drug Saf. 2021 Oct;44(10):1109-1119. doi: 10.1007/s40264-021-01107-6. Epub 2021 Aug 12.

  PMID: 34383289 DERIVED

MeSH Terms

Conditions

Spinal Muscular Atrophies of Childhood

Interventions

Zolgensma

Condition Hierarchy (Ancestors)

Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Sitra Tauscher-Wisniewski, MD

  Novartis Gene Therapies, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2019
• First Posted: August 1, 2019
• Study Start: February 10, 2020
• Primary Completion (Estimated): December 31, 2035
• Study Completion (Estimated): December 31, 2035
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

US (18); BE (2); FR (1); CA (1); IT (4); AU (1); GB (2); JP (1); TW (1)