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

Gemma Biotherapeutics

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Spinal Muscular Atrophy Type I

Treatments: Biological: GB221

Study type: Interventional

Funder types: Industry

Identifiers

NCT07070999

CHARISMA (Other Identifier)

GB221-101

Details and patient eligibility

About

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.

Enrollment: 22 estimated patients

Sex: All

Ages: 2 weeks to 12 months old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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22 participants in 4 patient groups

Cohort 1A, safety and exploratory efficacy of a single dose in symptomatic participants

Experimental group

Description:

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.

Treatment:

Biological: GB221

Cohort 1B, expansion phase for confirmatory testing in symptomatic participants

Experimental group

Description:

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.

Treatment:

Biological: GB221

Cohort 2A, safety and exploratory efficacy of a single dose in presymptomatic participants

Experimental group

Description:

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.

Treatment:

Biological: GB221

Cohort 2B, expansion phase for confirmatory testing in presymptomatic participants

Experimental group

Description:

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.

Treatment:

Biological: GB221