Summary
EudraCT Number:2021-006709-31
Sponsor's Protocol Code Number:COAV101B12302
National Competent Authority:Netherlands - Competent Authority
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2022-08-13
Trial results
A. Protocol Information
A.1Member State ConcernedNetherlands - Competent Authority
A.2EudraCT number2021-006709-31
A.3Full title of the trial
Phase IIIb, open-label, single-arm, multi-center study to evaluate the safety, tolerability and efficacy of OAV101 administered intrathecally (1.2 x 1014 vector genomes) to participants 2 to 12 years of age with spinal muscular atrophy (SMA) who have discontinued treatment with nusinersen (Spinraza®) or risdiplam (Evrysdi®)
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Phase IIIb, open-label, multi-center study to evaluate safety, tolerability and efficacy study of OAV101 administered intrathecally to participants with spinal muscular atrophy (SMA) who have discontinued treatment with nusinersen or risdiplam
A.3.2Name or abbreviated title of the trial where available
STRENGTH
A.4.1Sponsor's protocol code numberCOAV101B12302
A.7Trial is part of a Paediatric Investigation Plan Yes
A.8EMA Decision number of Paediatric Investigation PlanP/015/2022
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorNovartis Pharma AG
B.1.3.4CountrySwitzerland
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportNovartis Pharma AG
B.4.2CountrySwitzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationNovartis Pharma AG
B.5.2Functional name of contact pointClinical Trial Information Desk
B.5.3 Address:
B.5.3.1Street AddressForum 1, Novartis Campus
B.5.3.2Town/ cityBasel
B.5.3.3Post code4056
B.5.3.4CountrySwitzerland
B.5.4Telephone number+41 61 3241 111
B.5.5Fax number+41 61 3248 001
B.5.6E-mail[email protected]
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Zolgensma
D.2.1.1.2Name of the Marketing Authorisation holderNovartis Gene Therapies EU Limited
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
D.2.5.1Orphan drug designation numberEMA/OD/028/15
D.3 Description of the IMP
D.3.1Product nameOAV101
D.3.2Product code OAV101
D.3.4Pharmaceutical form Solution for injection
D.3.4.1Specific paediatric formulation Yes
D.3.7Routes of administration for this IMPIntrathecal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNOnasemnogene abeparvovec
D.3.9.1CAS number 1922968-73-7
D.3.9.2Current sponsor codeOAV101
D.3.9.3Other descriptive namepreviously termed sc.AAV9.CB.SMN and AVXS-101
D.3.9.4EV Substance CodeSUB193254
D.3.10 Strength
D.3.10.1Concentration unit Vector genome
D.3.10.2Concentration typeequal
D.3.10.3Concentration number40000000000000
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Yes
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product Yes
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Spinal Muscular Atrophy
E.1.1.1Medical condition in easily understood language
Spinal Muscular Atrophy
E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.1
E.1.2Level PT
E.1.2Classification code 10041582
E.1.2Term Spinal muscular atrophy
E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
E.1.3Condition being studied is a rare disease Yes
E.2 Objective of the trial
E.2.1Main objective of the trial
The primary objective of this study is to characterize the safety and tolerability of OAV101 intrathecal (IT) over a 52-week period in patients with SMA aged 2 to 12 years who have discontinued treatment with nusinersen (Spinraza®) or risdiplam (Evrysdi®).
E.2.2Secondary objectives of the trial
The secondary objective of this study is to assess the efficacy of OAV101 IT on motor function and caregiver impact over a 52-week period in patients with SMA aged 2 to 12 years who have discontinued treatment with nusinersen (Spinraza®) or risdiplam (Evrysdi®).
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
● Written informed consent
● SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations and any copy of SMN2 gene
● Aged 2 to 12 years at time of Screening Visit 1
● Have had at least four loading doses of nusinersen (Spinraza®) or at least 3 months of treatment with risdiplam (Evrysdi®) at Screening
● Must be able to sit independently but must never have taken steps independently
● Diagnosed through newborn or neonatal screening or patients clinically diagnosed must have age of clinical symptom onset < 18 months
● Meets age-appropriate institutional criteria for use of anesthesia/sedation
● Female participants who are sexually active or have reached menarche must have a negative pregnancy test at Screening. Those females who are sexually active must also agree to use highly effective methods of contraception.
E.4Principal exclusion criteria
● Excluding SMA, any medical condition considered clinically significant
● Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis
● Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer using an immunoassay is reported as elevated (reference to >1:50 or a validated result consistent with being elevated)
● Clinically significant abnormalities in test results during screening period and/or at Baseline
● Platelet count less than the lower limit of normal (LLN), or platelet transfusion within 1 month at Screening Visit 1
● Abnormal coagulation panel results at Screening
● Hepatic dysfunction (i.e. alanine aminotransferase (ALT), total bilirubin (TBL), gamma-glutamyl transferase (GGT) or glutamate dehydrogenase (GLDH) > upper limit of normal (ULN) at Screening (with the exception of isolated AST elevation: in the absence of other liver laboratory abnormalities, isolated elevated AST is not considered exclusionary)
● Contraindications for lumbar puncture procedure
● At Baseline (Day-1), participants are excluded if they received:
●nusinersen (Spinraza®) within 4 months at Baseline
● risdiplam (Evrysdi®) within 15 days at Baseline
● Vaccinations 2 weeks prior to administration of OAV101
● Hospitalization for a pulmonary event, or for nutritional support within 2 months prior to Screening or inpatient major surgery planned.
● Presence of the following:
● An active infectious process requiring systemic antiviral or antimicrobial therapy at any time between Screening Visit 1 and OAV101 administration, or
● An active but untreated viral or bacterial infectious process at any time between Screening Visit 1 and administration of OAV101, or
● Any febrile illness within two weeks prior to Screening Visit 1 and up to administration of OAV101
● Requiring invasive ventilation, awake noninvasive ventilation for > 6 hours during a 24-hour period, noninvasive ventilation for >12 hours during a 24-hour period or requiring tracheostomy, at Screening and up to OAV101 administration
● Concomitant use of any of the following medication categories within 90 days prior to administration of OAV101
● Ongoing immunosuppressive therapy (e.g., corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab), plasmapheresis, immunomodulators (e.g., adalimumab)
● History of hypersensitivity to any of the study treatments or its excipients or drugs of similar chemical classes
E.5 End points
E.5.1Primary end point(s)
The primary endpoints for the primary objectives are: the number and percentage of participants reporting adverse events (AEs), related AEs, serious AEs and adverse events of special interest (AESIs) over a 52-week period.
E.5.1.1Timepoint(s) of evaluation of this end point
52 weeks
E.5.2Secondary end point(s)
The secondary endpoints for the secondary objective questions of interest are:
● What is the change from baseline to Week 52 visit in the Hammersmith Functional Motor Scale Expanded (HFMSE) total score?
● What is the change from baseline to Week 52 visit in the Revised Upper Limb Module (RULM) total score?
● What is the change from baseline to Week 52 visit in Assessment of Caregiver Experience in Neuromuscular Disease (ACEND) instrument score?
E.5.2.1Timepoint(s) of evaluation of this end point
52 weeks
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic Yes
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others Yes
E.6.13.1Other scope of the trial description
Tolerability
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled No
E.8.1.1Randomised No
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial1
E.8.3 The trial involves single site in the Member State concerned Yes
E.8.4 The trial involves multiple sites in the Member State concerned No
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA8
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Australia
Belgium
Canada
France
Germany
Italy
Japan
Netherlands
Spain
United States
E.8.7Trial has a data monitoring committee Yes
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
Study completion is defined as when the last participant finishes their Study Completion visit and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator or, in the event of an early study termination decision, the date of that decision.
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years1
E.8.9.1In the Member State concerned months10
E.8.9.1In the Member State concerned days10
E.8.9.2In all countries concerned by the trial years2
E.8.9.2In all countries concerned by the trial months1
E.8.9.2In all countries concerned by the trial days10
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 Yes
F.1.1Number of subjects for this age range: 28
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) Yes
F.1.1.5.1Number of subjects for this age range: 24
F.1.1.6Adolescents (12-17 years) Yes
F.1.1.6.1Number of subjects for this age range: 4
F.1.2Adults (18-64 years) No
F.1.3Elderly (>=65 years) No
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state2
F.4.2 For a multinational trial
F.4.2.1In the EEA 13
F.4.2.2In the whole clinical trial 28
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
Participants from this study will be offered to participate in a planned long-term follow up (upto 15 years) study. The planned long-term study does not involve drug administration.
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2022-08-12
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2022-08-10
P. End of Trial
P.End of Trial StatusOngoing