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

NCT07070999 | Recruiting Phase 1 DMC

• 2 other identifiers: GB221-101CHARISMA
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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.

Conditions

Spinal Muscular Atrophy Type I

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (3)

• 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.

  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.

  Baseline, 6 months and 18 months post dose.

Study Arms (4)

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.

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.

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.

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.

Biological: GB221

Interventions

GB221 BIOLOGICAL

GB221

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

Eligibility Criteria

• Age: 2 Weeks - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gemma Biotherapeutics: lead

Study Sites (1)

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

RECRUITING

MeSH Terms

Conditions

Spinal Muscular Atrophies of Childhood

Condition Hierarchy (Ancestors)

Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• May Orfali, MD

  Gemma Biotherapeutics

  STUDY DIRECTOR

Central Study Contacts

Jenna Tress

CONTACT

445-895-3356; clinical_studies@gemmabiotx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2025
• First Posted: July 17, 2025
• Study Start: January 6, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): April 1, 2029
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)