Study of Safety, Tolerability and Efficacy of GB221 in Infants With Spinal Muscular Atrophy Type 1

June 26, 2026 updated by: Gemma Biotherapeutics

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:

  1. 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
  2. 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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
22

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Brazil
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
        • Recruiting
        • Hospital de Clinicas de Porto Alegre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Symptomatic Participants

    1. 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
    2. 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

    1. 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
    2. Participants must be 2 weeks to < 5 months (< 150 days) of age at the time of dosing.

Exclusion Criteria:

  1. Any suspected or confirmed active viral infection at screening baseline (including HIV, Hepatitis B or C, or human T Cell lymphotropic viruses [HTLV])
  2. History of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry <95% saturation.
  3. Ongoing immunosuppressive therapy or immunosuppressive therapy within 3 months of starting the trial (e.g. corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab)
  4. Participation in a recent SMA treatment clinical trial that, in the opinion of the Investigator, creates unnecessary risks for gene transfer.
  5. Prior history of gene therapy for any indication, hematopoietic transplant or solid organ transplant
  6. Subjects with severe scoliosis
  7. Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1A, safety and exploratory efficacy of a single dose in symptomatic participants
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.
Biological: GB221
GB221
Experimental: Cohort 1B, expansion phase for confirmatory testing in symptomatic participants
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.
Biological: GB221
GB221
Experimental: Cohort 2A, safety and exploratory efficacy of a single dose in presymptomatic participants
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.
Biological: GB221
GB221
Experimental: Cohort 2B, expansion phase for confirmatory testing in presymptomatic participants
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.
Biological: GB221
GB221

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Up to 18 months across multiple visits
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.
Up to 18 months across multiple visits
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.
Up to 18 months across multiple visits
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.
Up to 18 months across multiple visits
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.
Up to 18 months across multiple visits
Change in serum cardiac troponin I levels
Time Frame: Up to 18 months across multiple visits
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.
Up to 18 months across multiple visits
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.
Up to 18 months across multiple visits
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.
Up to 18 months across multiple visits

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Assess the number of participants who experience permanent ventilation or death
Time Frame: Up to 18 months across multiple visits
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.
  • 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.
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.
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.
Baseline, 6 months and 18 months post dose.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Gemma Biotherapeutics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: May Orfali, MD, Gemma Biotherapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 6, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 30, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 9, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 17, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 29, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 26, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GB221-101
  • CHARISMA (Other Identifier: Gemma Bio, Inc.)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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