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

NCT ID: NCT07070999

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2029-04-30

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. 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.

Conditions

Spinal Muscular Atrophy Type I

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

GB221

Intervention Type: BIOLOGICAL

GB221

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.

Group Type: EXPERIMENTAL

GB221

Intervention Type: BIOLOGICAL

GB221

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.

Group Type: EXPERIMENTAL

GB221

Intervention Type: BIOLOGICAL

GB221

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.

Group Type: EXPERIMENTAL

GB221

Intervention Type: BIOLOGICAL

GB221

Interventions

GB221

GB221

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 2 Weeks
• Maximum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gemma Biotherapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

May Orfali, MD

Role: STUDY_DIRECTOR

Gemma Biotherapeutics

Central Contacts

Jenna Tress

Role: CONTACT

clinical_studies@gemmabiotx.com

445-895-3356

Other Identifiers

CHARISMA

Identifier Type: OTHER

Identifier Source: secondary_id

GB221-101

Identifier Type: -

Identifier Source: org_study_id