Spinal Muscular Atrophy Type IPhase 1/2NCT07070999
Study of Safety, Tolerability and Efficacy of GB221 in Infants With Spinal Muscular Atrophy Type 1
A Phase 1/2 study testing GB221 in people with Spinal Muscular Atrophy Type I, run by Gemma Biotherapeutics at 1 site in Brazil.
Trial summary
GB221 is a gene therapy that delivers a working SMN1 gene to the motor neurons of people with spinal muscular atrophy (SMA) Type 1. This study will evaluate the safety, tolerability and efficacy of GB221 in two groups: 1. Read more about this study
- Who is it for?
- Ages 2 weeks to 12 months
- Conditions the study is for
- Spinal Muscular Atrophy Type I
- What is being tested?
- GB221
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteBrazil
- Study dates
- 6 Jan 2026to Apr 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 2 weeks to 12 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Symptomatic Participants
- Diagnosis of SMA Type 1 based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and up to 3 copies of SMN2
- Participants must be 2 weeks to < 12 months of age at the time of dosing with disease onset of during the first 6 months of life.
- Presymptomatic Participants
- At risk of SMA Type 1 based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and up to 2 copies of SMN2
- Participants must be 2 weeks to < 5 months (< 150 days) of age at the time of dosing.
Who cannot join
- Any suspected or confirmed active viral infection at screening baseline (including HIV, Hepatitis B or C, or human T Cell lymphotropic viruses [HTLV])
- History of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry <95% saturation.
- Ongoing immunosuppressive therapy or immunosuppressive therapy within 3 months of starting the trial (e.g. corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab)
- Participation in a recent SMA treatment clinical trial that, in the opinion of the Investigator, creates unnecessary risks for gene transfer.
- Prior history of gene therapy for any indication, hematopoietic transplant or solid organ transplant
- Subjects with severe scoliosis
- Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903
About this study
Official title: A Phase 1-2, Open-Label, Multicenter Study to Assess the Safety, Tolerability and Efficacy of a Single Dose of GB221 Delivered Into the Cisterna Magna of Pediatric Participants From 2 Weeks to Younger Than 12 Months of Age With Spinal Muscular Atrophy Type 1
GB221 is a gene therapy that delivers a working SMN1 gene to the motor neurons of people with spinal muscular atrophy (SMA) Type 1. This study will evaluate the safety, tolerability and efficacy of GB221 in two groups:
- participants aged from 2 weeks to younger than 12 months presenting with symptoms of SMA Type 1 who have never received a treatment OR are receiving the drug risdiplam
- participants aged from 2 weeks to younger than 5 months who are at risk of developing SMA Type 1 (presymptomatic) and have never received treatment OR are receiving the drug risdiplam.
- Conditions
- Spinal Muscular Atrophy Type I
- Being tested
- GB221
- 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.
GB221Biological
GB221
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1A, safety and exploratory efficacy of a single dose in symptomatic participants | Experimental | Symptomatic participants with SMA Type 1 (up to 3 copies of SMN2), who are either treatment naïve or receiving risdiplam, with onset of disease during the first 6 months of life, aged from 2 weeks to younger than 12 months at the time of dosing. Receives: Biological: GB221 |
| Cohort 1B, expansion phase for confirmatory testing in symptomatic participants | Experimental | Symptomatic participants with SMA Type 1 (up to 3 copies of SMN2), who are either treatment naïve or receiving risdiplam, with onset of disease during the first 6 months of life, aged from 2 weeks to younger than 12 months at the time of dosing. Receives: Biological: GB221 |
| Cohort 2A, safety and exploratory efficacy of a single dose in presymptomatic participants | Experimental | Presymptomatic participants (treatment naïve or receiving risdiplam) at risk of developing SMA Type 1 (up to 2 copies of SMN2), aged from 2 weeks to younger than 5 months (< 150 days) at the time of dosing. Receives: Biological: GB221 |
| Cohort 2B, expansion phase for confirmatory testing in presymptomatic participants | Experimental | Presymptomatic participants (treatment naïve or receiving risdiplam) at risk of developing SMA Type 1 (up to 2 copies of SMN2), aged from 2 weeks to younger than 5 months (< 150 days) at the time of dosing. Receives: Biological: GB221 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events (AEs) and serious adverse events (SAEs) at Grade 3 or higher as characterized by CTCAEv5.0
Assess the number of treatment-related AEs and SAEs as characterized by CTCAEv5.0
Measured: Up to 18 months across multiple visits
Number of Participants with Clinically Significant Changes in Physical Functions
Assess the number of participants with clinically significant changes in physical functions.
Measured: Up to 18 months across multiple visits
Number of Participants with Clinically Significant Changes in Neurological Functions
Assess the number of participants with clinically significant changes in neurological functions.
Measured: Up to 18 months across multiple visits
Number of Participants with Clinically Significant Changes in Vital signs
Assess the number of participants with clinically significant changes in vital signs.
Measured: Up to 18 months across multiple visits
Change in electrocardiogram results
ECG will measure RR interval, P Wave, PR interval, PR segment, QRS Complex, ST segment, T wave and QT Interval.
Measured: Up to 18 months across multiple visits
Change in serum cardiac troponin I levels
Measured: Up to 18 months across multiple visits
Number of Participants with Clinically Significant Laboratory Abnormalities as Measured Using Hematology, Chemistry and Coagulation Tests
Assess the number of participants with clinically significant laboratory changes including hematology, serum chemistry, and coagulation tests.
Measured: Up to 18 months across multiple visits
Number of Participants with Clinically Significant Laboratory Abnormalities as Measured Using Urine and CSF Tests
Assess the number of participants with clinically significant laboratory changes including urine and CSF tests.
Measured: Up to 18 months across multiple visits
Change in markers of immunogenicity
Assessment of humoral (NAb and TAb titers) and T-cell (IFNγ ELISpot) immune responses to the AAVhu68 capsid and SMN transgene product in serum and CSF.
Measured: Up to 18 months across multiple visits
Secondary outcomes (3)
Assess the number of participants who experience permanent ventilation or death
Measured: Up to 18 months across multiple visits
Percentage of infants with improvement in the motor milestones categories in Section 2 of the Hammersmith Infant Neurological Examination (HINE), with the exclusion of voluntary grasp.
- improvement in at least one category, i.e., an increase in the score for head control, rolling, sitting, crawling, standing, or walking of ≥1 point,
- an increase in the score for kicking of ≥2 points, or achievement of the maximal score for kicking.
Measured: Baseline, 6 months and 18 months post dose.
Change from baseline in mean Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) Score.
Assess 16 types of muscle movements, each given a score from zero (the person can't complete the movement) to 4 (the person can complete the movement on their own, without assistance) to produce a score of 0 to 64.
Measured: Baseline, 6 months and 18 months post dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2025
- Study start6 Jan 2026
- Primary completionDec 2028 (estimated)
- Study completionApr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gemma Biotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- May Orfali, MD, Study director, Gemma Biotherapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07070999
- Sponsor's protocol ID
- GB221-101
- Other IDs
- CHARISMA
- Status last verified
- Feb 2026
- First submitted
- 30 May 2025
- Last updated
- 29 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1-2, Open-Label, Multicenter Study to Assess the Safety, Tolerability and Efficacy of a Single Dose of GB221 Delivered Into the Cisterna Magna of Pediatric Participants From 2 Weeks to Younger Than 12 Months of Age With Spinal Muscular Atrophy Type 1
- ClinicalTrials.gov ID
- NCT07070999
- Acronym / sponsor ID
- GB221-101
- Conditions
- Spinal Muscular Atrophy Type I
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- Gemma BiotherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 6 Jan 2026 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Apr 2029 (estimated)
- First posted
- 17 Jul 2025 (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.
GB221 is a gene therapy that delivers a working SMN1 gene to the motor neurons of people with spinal muscular atrophy (SMA) Type 1. This study will evaluate the safety, tolerability and efficacy of GB221 in two groups:
- participants aged from 2 weeks to younger than 12 months presenting with symptoms of SMA Type 1 who have never received a treatment OR are receiving the drug risdiplam
- participants aged from 2 weeks to younger than 5 months who are at risk of developing SMA Type 1 (presymptomatic) and have never received treatment OR are receiving the drug risdiplam.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1A, safety and exploratory efficacy of a single dose in symptomatic participants | Experimental | Biological: GB221Symptomatic participants with SMA Type 1 (up to 3 copies of SMN2), who are either treatment naïve or receiving risdiplam, with onset of disease during the first 6 months of life, aged from 2 weeks to younger than 12 months at the time of dosing. |
| Cohort 1B, expansion phase for confirmatory testing in symptomatic participants | Experimental | Biological: GB221Symptomatic participants with SMA Type 1 (up to 3 copies of SMN2), who are either treatment naïve or receiving risdiplam, with onset of disease during the first 6 months of life, aged from 2 weeks to younger than 12 months at the time of dosing. |
| Cohort 2A, safety and exploratory efficacy of a single dose in presymptomatic participants | Experimental | Biological: GB221Presymptomatic participants (treatment naïve or receiving risdiplam) at risk of developing SMA Type 1 (up to 2 copies of SMN2), aged from 2 weeks to younger than 5 months (< 150 days) at the time of dosing. |
| Cohort 2B, expansion phase for confirmatory testing in presymptomatic participants | Experimental | Biological: GB221Presymptomatic participants (treatment naïve or receiving risdiplam) at risk of developing SMA Type 1 (up to 2 copies of SMN2), aged from 2 weeks to younger than 5 months (< 150 days) at the time of dosing. |
Who may qualify
- Ages
- 2 weeks to 12 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Symptomatic Participants
- Presymptomatic Participants
Key exclusion criteria (7 listed)
- Any suspected or confirmed active viral infection at screening baseline (including HIV, Hepatitis B or C, or human T Cell lymphotropic viruses [HTLV])
- History of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry <95% saturation.
- Ongoing immunosuppressive therapy or immunosuppressive therapy within 3 months of starting the trial (e.g. corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab)
- Participation in a recent SMA treatment clinical trial that, in the opinion of the Investigator, creates unnecessary risks for gene transfer.
- Prior history of gene therapy for any indication, hematopoietic transplant or solid organ transplant
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 |
|---|---|---|
| GB221GB221 | Biological | Cohort 1A, safety and exploratory efficacy of a single dose in symptomatic participants, Cohort 1B, expansion phase for confirmatory testing in symptomatic participants, Cohort 2A, safety and exploratory efficacy of a single dose in presymptomatic participants, Cohort 2B, expansion phase for confirmatory testing in presymptomatic participants |
Primary outcome
Number of participants with treatment-related adverse events (AEs) and serious adverse events (SAEs) at Grade 3 or higher as characterized by CTCAEv5.0
Time frame: Up to 18 months across multiple visits
Assess the number of treatment-related AEs and SAEs as characterized by CTCAEv5.0
Number of Participants with Clinically Significant Changes in Physical Functions
Time frame: Up to 18 months across multiple visits
Assess the number of participants with clinically significant changes in physical functions.
Number of Participants with Clinically Significant Changes in Neurological Functions
Time frame: Up to 18 months across multiple visits
Assess the number of participants with clinically significant changes in neurological functions.
Number of Participants with Clinically Significant Changes in Vital signs
Time frame: Up to 18 months across multiple visits
Assess the number of participants with clinically significant changes in vital signs.
Change in electrocardiogram results
Time frame: Up to 18 months across multiple visits
ECG will measure RR interval, P Wave, PR interval, PR segment, QRS Complex, ST segment, T wave and QT Interval.
Change in serum cardiac troponin I levels
Time frame: Up to 18 months across multiple visits
Number of Participants with Clinically Significant Laboratory Abnormalities as Measured Using Hematology, Chemistry and Coagulation Tests
Time frame: Up to 18 months across multiple visits
Assess the number of participants with clinically significant laboratory changes including hematology, serum chemistry, and coagulation tests.
Number of Participants with Clinically Significant Laboratory Abnormalities as Measured Using Urine and CSF Tests
Time frame: Up to 18 months across multiple visits
Assess the number of participants with clinically significant laboratory changes including urine and CSF tests.
Change in markers of immunogenicity
Time frame: Up to 18 months across multiple visits
Assessment of humoral (NAb and TAb titers) and T-cell (IFNγ ELISpot) immune responses to the AAVhu68 capsid and SMN transgene product in serum and CSF.
3 secondary outcomes
Assess the number of participants who experience permanent ventilation or death
Time frame: Up to 18 months across multiple visits
Percentage of infants with improvement in the motor milestones categories in Section 2 of the Hammersmith Infant Neurological Examination (HINE), with the exclusion of voluntary grasp.
Time frame: Baseline, 6 months and 18 months post dose.
Change from baseline in mean Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) Score.
Time frame: Baseline, 6 months and 18 months post dose.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2026.
- 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.
May Orfali, MD study director
Gemma Biotherapeutics
1 site 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 GB221 in people with Spinal Muscular Atrophy Type I, run by Gemma Biotherapeutics at 1 site in Brazil.
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 6 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Denise Reilly (267-718-7654, clinical_studies@gemmabiotx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events (AEs) and serious adverse events (SAEs) at Grade 3 or higher as characterized by CTCAEv5.0 (time frame: Up to 18 months across multiple visits). The study lists 9 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 29 Jun 2026.