Spinal Muscular Atrophy Type IPhase 1/2NCT05614531
Clinical Trial to Assess the Safety and Efficacy of EXG001-307 in Patients with Spinal Muscular Atrophy Type 1
A Phase 1/2 study testing EXG001-307 injection in people with Spinal Muscular Atrophy Type I, run by Guangzhou Jiayin Biotech Ltd at 2 sites in China.
Trial summary
The purpose of this trial is to evaluate safety and efficacy of intravenous delivery of EXG001-307 as a treatment of spinal muscular atrophy Type 1 (SMN1). Read more about this study
- Who is it for?
- Ages 1 day to 180 days
- Conditions the study is for
- Spinal Muscular Atrophy Type I
- What is being tested?
- EXG001-307 injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesChina
- Study dates
- 16 Feb 2023to Aug 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 1 day to 180 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- SMA was diagnosed by a bilaterally allelic SMN1 mutation (deletion or point mutation) gene with 2 copies of the SMN2 gene.
- On the day of dosing, the subject ' s age did not exceed postnatal Day 180.
- The clinical history and signs were consistent with type 1 SMA manifestations, i.e. hypotonia, delayed motor function development, poor head control, round shoulder posture, and joint hypermobility.
- The subject's legal guardian understands the purpose, possible risks and interests of the study, agrees to participate in the study, completes all study procedures, tests and visits, and voluntarily signs the informed consent form.
- During the study, the subject's legal guardian was willing to perform standard treatment requirements such as nasogastric feeding, noninvasive mechanical ventilation, and expectoration machine as recommended by the investigator.
Who cannot join
- Gestational age at birth was less than 35 weeks (245 days).
- At screening, the subject had an oxygen saturation < 96% while awake or sleeping and did not receive any supplemental oxygen or respiratory support.
- Requirement of invasive ventilation or tracheotomy, or current use of noninvasive ventilatory support for an average of ≥ 16 hours/day.
- Weighed below the 3rd percentile by age according to the WHO Child Growth Criteria (WHO 2009).
- Before administration, if the subject has not received or delayed vaccination according to the current month-old national vaccination plan, it will significantly affect the safety of the subject as assessed by the investigator and the medical manager of the project team;
- Active viral infections (including HIV, COVID-19, hepatitis B or C seropositivity, torch virus, Epstein-Barr virus, and syphilis).
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- Serious non-respiratory disease within 2 weeks prior to screening.
- Upper respiratory tract infection or lower respiratory tract infection within 4 weeks prior to screening.
- Current presence of other severe infections or diseases.
- Known cardiac disease or ECG abnormalities that are clinically significant.
- Known hypersensitivity to prednisolone, other glucocorticoids, or its excipients.
- Immunosuppressive therapy (eg, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, rituximab) other than protocol-required prophylaxis within 3 months prior to dosing.
- Immunomodulatory drugs (eg, thymosin, interferon, etc.) are being used to treat myopathy, neuritis, diabetes mellitus (eg, immunosuppressants, glucocorticoids, insulin).
- Anti-AAV9 antibody titer > 1: 50 (as determined by ECL). If the potential subject has an anti-AAV9 antibody titer > 1: 50, it can be retested during the screening period. If the anti-AAV9 antibody titer is ≤ 1: 50 at the retest, the subject may continue to participate in the screening.
- Clinically significant abnormal laboratory values (GGT, ALT, and AST > 2.5 × ULN, bilirubin ≥ 3.0 mg/dL, creatinine ≥ 1.0 mg/dL, hemoglobin < 8 or > 18 g/dL; white blood cell count > 20,000/cm3; platelet count < 100,000/cm3).
- Prior use of other SMA therapeutic agents (e.g., nosinasenat, rispolam, and Zolgensma, etc.) or participated in clinical studies with other SMA therapeutic agents (including but not limited to the above 3 drugs).
- Major surgery is expected during study treatment.
- Other circumstances that, in the judgment of the investigator, are not suitable for participation in this study.
Trial locations and contacts
2 sites in 1 country.
China2 sites
The Children'S Hospital Zhejiang University of Medicine
Hangzhou, Zhejiang, 310051
The Children's Hospital of Fudan University
Shanghai, Shanghai Municipality, 201100
About this study
Official title: A Multicenter, Nonrandomized, Open-label,Dose Escalation Clinical Trial to Assess the Safety and Efficacy of EXG001 307 After Intravenous Injection in Patients with Spinal Muscular Atrophy Type 1
The purpose of this trial is to evaluate safety and efficacy of intravenous delivery of EXG001-307 as a treatment of spinal muscular atrophy Type 1 (SMN1).
Read the detailed description
The study will evaluate safety and efficacy of gene therapy in spinal muscular atrophy Type 1 (SMA1) patients. SMA is caused by low levels of the survival motor neuron (SMN) protein, and affects all muscles in the body. There is no effective treatment for SMA and current drug therapy has been unsuccessful in stabilizing or reversing this disease. Only supportive care is currently possible.
Open-label, dose-escalation clinical trial of EXG001-307 injected intravenously through a peripheral limb vein. Short-term safety will be evaluated over a 1.5 year period. Patients will be tested at baseline and return for follow up visits on days 14, 21, 30, followed by once every month through 12 months post dose, and then every three months through a year and a half post infusion. Unscheduled visits may occur if the PI determines that they are necessary.
The primary analysis for efficacy will be assessed when all patients reach 18 months of age (a database lock will be performed at the time point at which all patients reach 18 months of age). A follow-up safety analysis will be completed at the time point at which the last patient reaches 18 months of age after post-dose.
Upon completion of the 1.5-year study period, patients will be monitored annually as per standard of care for up to 5 years.
- Conditions
- Spinal Muscular Atrophy Type I
- Being tested
- EXG001-307 injection
- Keywords
- SMA,SMA1
- Medical subject headings
- Spinal Muscular Atrophies of Childhood
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EXG001-307 injectionGenetic
non-replicating, rAAV vector based on AAV9 containing cDNA encoding the human SMN protein.
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation- Cohort 1 | Experimental | dose 1 of EXG001-307 delivered one-time through a venous catheter inserted into a peripheral vein (n=3~6) Receives: Genetic: EXG001-307 injection |
| Dose escalation-Cohort 2 | Experimental | dose 2 of EXG001-307 delivered one-time through a venous catheter inserted into a peripheral vein (n=6~12) Receives: Genetic: EXG001-307 injection |
| Dose escalation-Cohort 3 | Experimental | dose 3 of EXG001-307 delivered one-time through a venous catheter inserted into a peripheral vein (n=3~6) Receives: Genetic: EXG001-307 injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety and tolerability of EXG001-307 following a single intravenous infusion
including type and incidence of AE, SAE, AESI, vital signs, physical/neurological examination, immunogenicity, virology, injection/infusion site reactions, 12-lead electrocardiogram, and safety laboratory results recorded
Measured: During each visit
Secondary outcomes (2)
Patients number who survival at 14 month of age
survival at 14 months of age was defined as the number of participants who did not die, did not require permanent ventilation (defined as absence of acute reversible disease [excluding perioperative ventilation], requiring tracheotomy or respiratory assistance with non-invasive ventilation support for ≥16 hours per day for ≥14 consecutive days) and did not withdraw from the study by 14 months of age.
Measured: up to 14 month of age
Number of patients who were able to sit unsupported for ≥30 seconds
According to the Bailey Scale of Infant and Child Development Version 3 (BSID-III) ,sit unsupported as a participant who sits up straight with head erect for at least 30 seconds; participant does not use arms or hands to balance body or support position, evaluation procedure will confirmed by video recording
Measured: From Day 1 up to 18 Months of Age Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2022
- Study start16 Feb 2023
- Primary completionAug 2025 (estimated)
- Study completionAug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Spinal Muscular Atrophy Type IStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangzhou Jiayin Biotech Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05614531
- Sponsor's protocol ID
- EXG001-307-102
- Other IDs
- 2022LP00989
- Status last verified
- Sep 2024
- First submitted
- 2 Nov 2022
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Song C, Wang Q, Zhu P, Li J, Dai L, Hu W, Yang W, Zhang R, Wang D, Li Z, Chen S, Wang L, Ye G, Wu Z. Efficacy and preliminary safety assessment of EXG001-307 AAV gene therapy for spinal muscular atrophy. Mol Ther Methods Clin Dev. 2025 Apr 18;33(2):101475. doi: 10.1016/j.omtm.2025.101475. eCollection 2025 Jun 12.
PubMed 40458203
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Nonrandomized, Open-label,Dose Escalation Clinical Trial to Assess the Safety and Efficacy of EXG001 307 After Intravenous Injection in Patients with Spinal Muscular Atrophy Type 1
- ClinicalTrials.gov ID
- NCT05614531
- Acronym / sponsor ID
- EXG001-307-102
- Conditions
- Spinal Muscular Atrophy Type I
- Keywords
- SMA,SMA1
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Guangzhou Jiayin Biotech LtdIndustry (pharma, biotech, devices)
- Study start
- 16 Feb 2023 (actual)
- Primary completion
- Aug 2025 (estimated)
- Study completion
- Aug 2025 (estimated)
- First posted
- 14 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to evaluate safety and efficacy of intravenous delivery of EXG001-307 as a treatment of spinal muscular atrophy Type 1 (SMN1).
Detailed description
The study will evaluate safety and efficacy of gene therapy in spinal muscular atrophy Type 1 (SMA1) patients. SMA is caused by low levels of the survival motor neuron (SMN) protein, and affects all muscles in the body. There is no effective treatment for SMA and current drug therapy has been unsuccessful in stabilizing or reversing this disease. Only supportive care is currently possible.
Open-label, dose-escalation clinical trial of EXG001-307 injected intravenously through a peripheral limb vein. Short-term safety will be evaluated over a 1.5 year period. Patients will be tested at baseline and return for follow up visits on days 14, 21, 30, followed by once every month through 12 months post dose, and then every three months through a year and a half post infusion. Unscheduled visits may occur if the PI determines that they are necessary.
The primary analysis for efficacy will be assessed when all patients reach 18 months of age (a database lock will be performed at the time point at which all patients reach 18 months of age). A follow-up safety analysis will be completed at the time point at which the last patient reaches 18 months of age after post-dose.
Upon completion of the 1.5-year study period, patients will be monitored annually as per standard of care for up to 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose escalation- Cohort 1 | Experimental | Genetic: EXG001-307 injectiondose 1 of EXG001-307 delivered one-time through a venous catheter inserted into a peripheral vein (n=3~6) |
| Dose escalation-Cohort 2 | Experimental | Genetic: EXG001-307 injectiondose 2 of EXG001-307 delivered one-time through a venous catheter inserted into a peripheral vein (n=6~12) |
| Dose escalation-Cohort 3 | Experimental | Genetic: EXG001-307 injectiondose 3 of EXG001-307 delivered one-time through a venous catheter inserted into a peripheral vein (n=3~6) |
Who may qualify
- Ages
- 1 day to 180 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- SMA was diagnosed by a bilaterally allelic SMN1 mutation (deletion or point mutation) gene with 2 copies of the SMN2 gene.
- On the day of dosing, the subject ' s age did not exceed postnatal Day 180.
- The clinical history and signs were consistent with type 1 SMA manifestations, i.e. hypotonia, delayed motor function development, poor head control, round shoulder posture, and joint hypermobility.
- The subject's legal guardian understands the purpose, possible risks and interests of the study, agrees to participate in the study, completes all study procedures, tests and visits, and voluntarily signs the informed consent form.
- During the study, the subject's legal guardian was willing to perform standard treatment requirements such as nasogastric feeding, noninvasive mechanical ventilation, and expectoration machine as recommended by the investigator.
Key exclusion criteria (18 listed)
- Gestational age at birth was less than 35 weeks (245 days).
- At screening, the subject had an oxygen saturation < 96% while awake or sleeping and did not receive any supplemental oxygen or respiratory support.
- Requirement of invasive ventilation or tracheotomy, or current use of noninvasive ventilatory support for an average of ≥ 16 hours/day.
- Weighed below the 3rd percentile by age according to the WHO Child Growth Criteria (WHO 2009).
- Before administration, if the subject has not received or delayed vaccination according to the current month-old national vaccination plan, it will significantly affect the safety of the subject as assessed by the investigator and the medical manager of the project team;
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 |
|---|---|---|
| EXG001-307 injectionnon-replicating, rAAV vector based on AAV9 containing cDNA encoding the human SMN protein. | Genetic | Dose escalation- Cohort 1, Dose escalation-Cohort 2, Dose escalation-Cohort 3 |
Primary outcome
To evaluate the safety and tolerability of EXG001-307 following a single intravenous infusion
Time frame: During each visit
including type and incidence of AE, SAE, AESI, vital signs, physical/neurological examination, immunogenicity, virology, injection/infusion site reactions, 12-lead electrocardiogram, and safety laboratory results recorded
2 secondary outcomes
Patients number who survival at 14 month of age
Time frame: up to 14 month of age
Number of patients who were able to sit unsupported for ≥30 seconds
Time frame: From Day 1 up to 18 Months of Age Visit
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Derived from this study: PubMed 40458203Song C, Wang Q, Zhu P, Li J, Dai L, Hu W, Yang W, Zhang R, Wang D, Li Z, Chen S, Wang L, Ye G, Wu Z. Efficacy and preliminary safety assessment of EXG001-307 AAV gene therapy for spinal muscular atrophy. Mol Ther Methods Clin Dev. 2025 Apr 18;33(2):101475. doi: 10.1016/j.omtm.2025.101475. eCollection 2025 Jun 12.
- Individual participant dataSharing planned: No
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing EXG001-307 injection in people with Spinal Muscular Atrophy Type I, run by Guangzhou Jiayin Biotech Ltd at 2 sites in China.
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 5 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
To evaluate the safety and tolerability of EXG001-307 following a single intravenous infusion (time frame: During each visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05614531, which also lists 1 linked publication.
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 19 Sep 2024.