Muscular Atrophy, SpinalPhase 4OFELIANCT05073133
Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA) (OFELIA)
A Phase 4 study testing OAV101 in people with Muscular Atrophy, Spinal, run by Novartis Pharmaceuticals at 5 sites in 2 countries.
Trial summary
This was a phase IV Open-label, single-arm, single-dose, multicenter study, to evaluate the safety, tolerability and efficacy of intravenous administration of OAV101 (AVXS-101) in patients with SMA with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene ≤ 24 months and weighing ≤ 17 kg, over a 18-month… Read more about this study
- Who is it for?
- Ages Up to 24 months
- Conditions the study is for
- Muscular Atrophy, Spinal
- What is being tested?
- OAV101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 4 Nov 2021to 8 Aug 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 24 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Written informed consent/assent obtained prior to any assessment performed
- Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and any copy of SMN2 gene.
- Age ≤ 24 months of age at time of treatment
- 3. Weight ≤17 kg at the time of Screening Period 4. Naïve to treatment or have discontinued an approved drug/therapy 5. Up-to date on recommended childhood vaccinations and RSV prophylaxis with palivizumab (also known as Synagis), per local standard of care
Who cannot join
- Previous use of OAV101 or any AAV9 gene therapy
- Participant with history of aspiration pneumonia or signs of aspiration (eg, coughing or sputtering of food) within 4 weeks prior to Screening
- Participant dependent on gastrostomy feeding tube for 100% of nutritional intake.
- Anti-AAV9 antibody titer > 1:50 as determined by ligand binding immunoassay at the time of screening
- Inability to take corticosteroids
- Concomitant use of immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, or immunosuppressive therapy within 3 months prior to gene replacement therapy (eg, cyclosporine, tacrolimus, methotrexate, rituximab cyclophosphamide, IV immunoglobulin)
Show all 9Show fewer
- Hepatic dysfunction (i.e. AST, ALT, bilirubin, GGT or GLDH, ≥ ULN; CTCAE ≥ 1) at Screening (with the exception of isolated AST elevation: in the absence of other liver laboratory abnormalities, isolated AST elevation is not considered exclusionary)
- Previously treated with nusinersen (Spinraza®) within 4 months prior to Screening
- Previously treated with risdiplam (EvrysdiTM) within 15 days prior to Screening (washout period of at least 5 half-lives before Screening)
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Brazil3 sites
Novartis Investigative Site
Belo Horizonte, Minas Gerais, 30130-000
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90035-903
Novartis Investigative Site
São Paulo, São Paulo, 05403-000
Argentina2 sites
Novartis Investigative Site
Buenos Aires, C1245AAM
Novartis Investigative Site
CABA, Buenos Aires, C1181ACH
About this study
Official title: A Phase IV Open-label, Single-arm, Single-dose, Multicenter Study to Evaluate the saFEty, toLerability and effIcacy of Gene Replacement Therapy With intravenousOAV101(AVXS101) in Pediatric Patients From Latin America With Spinal Muscular Atrophy (SMA) - OFELIA
This was a phase IV Open-label, single-arm, single-dose, multicenter study, to evaluate the safety, tolerability and efficacy of intravenous administration of OAV101 (AVXS-101) in patients with SMA with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene ≤ 24 months and weighing ≤ 17 kg, over a 18-month period post infusion.
Read the detailed description
This is an open-label, single arm, multi-center study to evaluate the safety, tolerability, and efficacy of IV OAV101 in symptomatic SMA pediatric participants. The study enrolled participants ≤ 24 months old that weigh ≤ 17 kg. Participants who met eligibility criteria at Screening and Baseline visits received a single dose of IV OAV101 t the approved dose of 1.1e14 vg/kg and were followed for 18 months. The study included a 20-day screening period in which there were 2 Screening visits, during which, eligibility was assessed (Screening 1), weight was collected for dose calculation (Screening 2), and baseline assessments were performed prior to treatment.
On Day -1, participants were admitted to the hospital for pre-treatment baseline procedures including prednisolone treatment per study protocol. On Day 1, participants received a single IV infusion of OAV101. Participants were discharged 12-48 hours after the infusion, based on Investigator judgment. Safety monitoring was performed on an ongoing basis per protocol requirement and was evaluated by the clinical safety team as well as DMC (Data monitoring committee).
- Conditions
- Muscular Atrophy, Spinal
- Being tested
- OAV101
- Keywords
- Zolgensma, OAV101, AVXS 101, gene therapy, Muscle atrophy, SBMA, spinal and bulbar muscular atrophy, spinal muscular atrophy, bulbar muscular atrophy, muscle function, myopathy, muscle wasting, atrophied muscle, loss of muscle strength
- Medical subject headings
- Muscular Atrophy, Spinal, Muscular Atrophy, Bulbo-Spinal Atrophy, X-Linked, Muscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OAV101Genetic
Also called AVXS-101, Zolgensma
A single Gene Therapy IV infusion at 1.1e14 vector genome (vg)/kg over approximately 60 minutes
| Study group | Role | What they receive |
|---|---|---|
| OAV101 | Experimental | A single IV infusion at 1.1e14 vector genome (vg)/kg over approximately 60 minutes Receives: Genetic: OAV101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Emergent AEs and SAEs
An AE is any untoward medical occurrence (eg 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. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.
Changes from baseline in vital signs, cardiac safety assessments, and clinical laboratory results are reported as Adverse Events if clinically significant and as applicable, per investigator assessment.
Measured: Up to Month 18
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
An AE is any untoward medical occurrence (eg 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. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.
Adverse events of special interest (AESI) are defined by the important identified risk and important potential risk: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Sensory abnormalities suggestive of ganglionopathy, and Thrombotic microangiopathy. These were assessed by the investigator.
Measured: Up to Month 18
Secondary outcomes (1)
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
The World Health Organization-Multicentre Growth Reference Study (WHO-MGRS) was used to measure developmental motor milestones. This was assessed via the milestone checklist. The 6 developmental milestones are: sitting without support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone and walking alone. A yes response indicates that the patient reached a particular development milestone.
Measured: Baseline (Screening), and at Weeks 26, 52 and 78
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2021
- Study start4 Nov 2021
- Primary completion8 Aug 2023
- Study completion8 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Muscular Atrophy, SpinalStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- OAV101 will be administered as a single IV infusion at 1.1e14 vg/kg over approximately 60 minutes
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05073133
- Sponsor's protocol ID
- COAV101A1IC01
- Other IDs
- 2023-000864-67, 2023
- Acronym
- OFELIA
- Status last verified
- Oct 2024
- First submitted
- 20 Sep 2021
- Last updated
- 9 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IV Open-label, Single-arm, Single-dose, Multicenter Study to Evaluate the saFEty, toLerability and effIcacy of Gene Replacement Therapy With intravenousOAV101(AVXS101) in Pediatric Patients From Latin America With Spinal Muscular Atrophy (SMA) - OFELIA
- ClinicalTrials.gov ID
- NCT05073133
- Acronym / sponsor ID
- OFELIA / COAV101A1IC01
- Conditions
- Muscular Atrophy, Spinal
- Keywords
- Zolgensma, OAV101, AVXS 101, gene therapy, Muscle atrophy, SBMA, spinal and bulbar muscular atrophy, spinal muscular atrophy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 4 Nov 2021 (actual)
- Primary completion
- 8 Aug 2023 (actual)
- Study completion
- 8 Aug 2023 (actual)
- First posted
- 11 Oct 2021 (actual)
- Results
- Posted 31 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a phase IV Open-label, single-arm, single-dose, multicenter study, to evaluate the safety, tolerability and efficacy of intravenous administration of OAV101 (AVXS-101) in patients with SMA with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene ≤ 24 months and weighing ≤ 17 kg, over a 18-month period post infusion.
Detailed description
This is an open-label, single arm, multi-center study to evaluate the safety, tolerability, and efficacy of IV OAV101 in symptomatic SMA pediatric participants. The study enrolled participants ≤ 24 months old that weigh ≤ 17 kg. Participants who met eligibility criteria at Screening and Baseline visits received a single dose of IV OAV101 t the approved dose of 1.1e14 vg/kg and were followed for 18 months. The study included a 20-day screening period in which there were 2 Screening visits, during which, eligibility was assessed (Screening 1), weight was collected for dose calculation (Screening 2), and baseline assessments were performed prior to treatment.
On Day -1, participants were admitted to the hospital for pre-treatment baseline procedures including prednisolone treatment per study protocol. On Day 1, participants received a single IV infusion of OAV101. Participants were discharged 12-48 hours after the infusion, based on Investigator judgment. Safety monitoring was performed on an ongoing basis per protocol requirement and was evaluated by the clinical safety team as well as DMC (Data monitoring committee).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- OAV101 will be administered as a single IV infusion at 1.1e14 vg/kg over approximately 60 minutes
| Arm | Type | Receives |
|---|---|---|
| OAV101 | Experimental | Genetic: OAV101A single IV infusion at 1.1e14 vector genome (vg)/kg over approximately 60 minutes |
Who may qualify
- Ages
- Up to 24 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Written informed consent/assent obtained prior to any assessment performed
- Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and any copy of SMN2 gene.
- Age ≤ 24 months of age at time of treatment
- 3. Weight ≤17 kg at the time of Screening Period 4. Naïve to treatment or have discontinued an approved drug/therapy 5. Up-to date on recommended childhood vaccinations and RSV prophylaxis with palivizumab (also known as Synagis), per local standard of care
Key exclusion criteria (9 listed)
- Previous use of OAV101 or any AAV9 gene therapy
- Participant with history of aspiration pneumonia or signs of aspiration (eg, coughing or sputtering of food) within 4 weeks prior to Screening
- Participant dependent on gastrostomy feeding tube for 100% of nutritional intake.
- Anti-AAV9 antibody titer > 1:50 as determined by ligand binding immunoassay at the time of screening
- Inability to take corticosteroids
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OAV101Also: AVXS-101, ZolgensmaA single Gene Therapy IV infusion at 1.1e14 vector genome (vg)/kg over approximately 60 minutes | Genetic | OAV101 |
Primary outcome
Number of Participants With Treatment Emergent AEs and SAEs
Time frame: Up to Month 18
An AE is any untoward medical occurrence (eg 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. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. Changes from baseline in vital signs, cardiac safety assessments, and clinical laboratory results are reported as Adverse Events if clinically significant and as applicable, per investigator assessment.
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
Time frame: Up to Month 18
An AE is any untoward medical occurrence (eg 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. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. Adverse events of special interest (AESI) are defined by the important identified risk and important potential risk: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Sensory abnormalities suggestive of ganglionopathy, and Thrombotic microangiopathy. These were assessed by the investigator.
1 secondary outcome
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Time frame: Baseline (Screening), and at Weeks 26, 52 and 78
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.
Related trials for Muscular Atrophy, Spinal
Active, not recruitingPhase 4
A Study Evaluating the Effectiveness and Safety of Risdiplam Administered as an Early Intervention in Pediatric Participants With Spinal Muscular Atrophy After Gene Therapy
Muscular Atrophy, Spinal
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
RecruitingObservational study
A Study of Risdiplam in Participants With Type I and Type II Spinal Muscle Atrophy (SMA)
Spinal Muscle Atrophy
RecruitingPhase 3
A Study to Learn About the Investigational Drug Rinzimetostat (ORIC-944) in Patients With mCRPC Who Were Previously Treated With Abiraterone Acetate (Himalayas-1)
Metastatic Castration Resistant Prostate Cancer
Recruiting
Assessment of a Portable Digital Device for Quantified Analysis of Markerless Walking in Volunteers With Neuromuscular Diseases or Asymptomatic Volunteers
Spinal Muscular Atrophy (SMA), Charcot-Marie-Tooth
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing OAV101 in people with Muscular Atrophy, Spinal, run by Novartis Pharmaceuticals at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Brazil, Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment Emergent AEs and SAEs (time frame: Up to Month 18). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2024.