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

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: Recruiting
• Conditions: Spinal Muscular Atrophy Type I
• Intervention / Treatment: Biological: GB221

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jenna Tress; Phone Number: 445-895-3356; Email: clinical_studies@gemmabiotx.com

Study Locations

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

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

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	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	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	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	Assess the number of participants with clinically significant changes in vital signs.	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.	Up to 18 months across multiple visits
Change in serum cardiac troponin I levels		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.	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.	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.	Up to 18 months across multiple visits

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the number of participants who experience permanent ventilation or death		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.	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.	Baseline, 6 months and 18 months post dose.

Collaborators and Investigators

• Sponsor: Gemma Biotherapeutics
• Investigators: Study Director: May Orfali, MD, Gemma Biotherapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: May 30, 2025
• First Submitted That Met QC Criteria: July 9, 2025
• First Posted (Actual): July 17, 2025

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy, Spinal; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Spinal Muscular Atrophies of Childhood
• Other Study ID 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