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
Conditions
Interventions
Trade Name: Zolgensma
Product Name: OAV101
Product Code: AVXS-101
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ONASEMNOGENE ABEPARVOVEC
CAS Number: 1922968-73-7
Current Sponsor cod
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic survival motor neuron 1 (SMN1) mutations (deletion or point mutations) and any copy of the survival motor neuron 2 (SMN2) gene. Weight = 8.5 kg and = 21 kg at the time of Screening Visit 2 Naive to treatment or have discontinued an approved drug/therapy other protocol-defined inclusion criteria may apply Are the trial subjects under 18? yes Number of subjects for this age range: 24 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
Exclusion criteria: Previous OAV101 use or previous use of any AAV9 gene therapy Body Mass Index (BMI) 1:50 as determined by ligand binding immunoassay at the time of screening History of gene therapy, hematopoietic transplantation, or solid organ transplantation other protocol-defined exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of IV OAV101 over a 12-month period in participants with SMA weighing = 8.5 kg and = 21 kg ;Secondary Objective: To determine the efficacy of IV OAV101 at 6 and 12 months post dose in participants with SMA weighing = 8.5 kg and = 21 kg as measured by change from baseline in: · Developmental motor milestone achievement as assessed by World Health Organization-Multicentre Growth Reference Study (WHO-MGRS) and Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) criteria · Hammersmith Functional Motor Scale - Expanded (HFMSE) · Revised Upper Limb Module (RULM), as appropriate according to participant age ;Primary end point(s): Number of participants with treatment emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Number of participants with important identified and important potential risks (Adverse Events of Special Interest (AESI)) The following are important identified and important potential risks (AESI) associated with OAV101: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Sensory abnormalities suggestive of ganglionopathy, and Thrombotic microangiopathy. These will be assessed by the investigator. Change from baseline in vital signs measurements - systolic and diastolic blood pressure (mmHg) Change from baseline in vital signs measurements - respiratory rate (breaths per minute) Change from baseline in vital signs measurements - pulse (beats per minute) Change from baseline in vital signs measurements - temperature (degrees Celsius) Change from baseline in vital signs measurements - oxygen saturation level (%);Timepoint(s) of evaluation of this end point: up to 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: up to 12 months;Secondary end point(s): Achievement of development motor milestones according to the Bayley Scale of Infant and Toddler Development. Developmental motor milestones are assessed via the developmental milestone checklist, formed of 10 yes/no questions with optional video documentation. 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. A yes response indicates that the patient reached a particular development milestone. Change from baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE), as appropriate according to participant age 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 indicated higher levels of motor ability. Change from baseline in Revised Upper Limb Module (RULM), as appropriate according to participant age. The RULM assesses motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. 'The scale consists of an entry item to establish functional levels and 19 items covering distal to proximal movements. The entry item is a modified version of the Brooke scale, including activities ranging from no functional use of hands (score 0) to full bilateral shoulder abduction (score 6). The entry item does not contribute to the total score but serves as a functional classification of overall upper limb functional ability. Of the remaining 19 items, 18 are scored on a 3 point scoring system and 1 item is scored on a 2 point scoring system. The test is performed unilaterally using the limb prefer | — |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Portugal, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactInformation&Communication Médicales
Novartis Pharma SAS
Outcome results
None listed