GB221 gene therapy for 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

This study will test whether a single dose of GB221, a gene therapy that provides a working SMN1 gene, is safe and helps infants with SMA Type 1, including symptomatic babies up to 12 months and presymptomatic babies under 5 months (some may be on risdiplam).

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 22 (estimated)
• Ages: 2 Weeks to 12 Months
• Sex: All
• Sponsor: Gemma Biotherapeutics (Industry-sponsored)
• Drugs / interventions: rituximab, methotrexate, cyclophosphamide
• Locations: 1 site (Porto Alegre, Rio Grande do Sul)
• Trial ID: NCT07070999 on ClinicalTrials.gov

What this trial studies

GB221 is an AAV-based gene therapy designed to deliver a functional SMN1 gene to motor neurons. This phase 1/2 interventional trial enrolls two cohorts: symptomatic infants aged 2 weeks to under 12 months (up to 3 SMN2 copies) and presymptomatic infants aged 2 weeks to under 5 months (up to 2 SMN2 copies), with participants allowed to be treatment-naïve or receiving risdiplam. Participants will receive GB221 and be followed for safety, tolerability, and measures of motor function and survival. The study is being conducted at Hospital de Clínicas de Porto Alegre in Brazil.

Who should consider this trial

Good fit: Infants with genetically confirmed bi-allelic SMN1 mutations who are 2 weeks to under 12 months with symptoms (up to 3 SMN2 copies) or 2 weeks to under 5 months presymptomatic (up to 2 SMN2 copies), who are treatment-naïve or receiving risdiplam, are the intended candidates.

Not a fit: Babies with active viral infections, a history of invasive ventilatory support or low oxygen saturation (<95%), recent immunosuppressive therapy, those outside the specified age or SMN2 copy ranges, or who are otherwise medically unstable are unlikely to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, GB221 could provide a durable source of functional SMN protein after a single dose, improving motor milestones and survival in infants with SMA Type 1.

How similar studies have performed: AAV-based SMN1 gene therapies such as onasemnogene abeparvovec have previously produced substantial clinical benefit in infants with SMA Type 1, so this approach builds on established successes.

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.

Where this trial is running

Porto Alegre, Rio Grande do Sul

• Hospital de Clínicas de Porto Alegre — Porto Alegre, Rio Grande do Sul, Brazil (Recruiting)

Study contacts

• Study coordinator: Jenna Tress

Conditions Spinal Muscular Atrophy Type I