Clinical Trial to Evaluate the Safety and Efficacy of EXG001-307 in Patients With Spinal Muscular Atrophy Type I

NCT06576388 | Completed Early Phase 1 DMC

• 1 other identifier: EXG001-307-101
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to evaluate the safety and preliminary efficacy of a single intravenous injection of exg001-307 in patients with type I spinal muscular atrophy. The research process includes the screening period (the screening period is from the time the subject signs the informed consent to the time before hormone pretreatment, with a maximum of 28 days), the treatment period (the subject receives hospitalization and observation including hormone pretreatment and single infusion of study drugs), and the follow-up period (the end of the treatment period until the subject reaches the age of 18 months, loss of follow-up, active withdrawal from the study or death). The qualified subjects in the screening period enter the treatment period, receive exg001-307 treatment, and enter the follow-up period after hospitalization observation. At the end of the study visit (subjects 18 months old), eligible subjects will be asked to transfer to the long-term follow-up study.

Conditions

Type I Spinal Muscular Atrophy

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety and tolerability of EXG001-307 after a single intravenous infusion

  including type and incidence of AE, SAE, AESI, vital signs, physical/neurological examination, immunogenicity, virology, injection/infusion site reactions, 12-lead electrocardiogram, and safety laboratory results recorded

  up to 18months

Secondary Outcomes (1)

• Explore a safe and effective dose range；Assess initial effectiveness；

  up to 18 months

Study Arms (1)

single Arm-experimental group

EXPERIMENTAL

The dose escalation study included two cohorts with three dose levels: 0.67×1014 vg/kg, 1.1×1014 vg/kg, and 1.5×1014 vg/kg. Among them, the first queue contains two levels, the first dose levels (0.67 x 1014 vg/kg) using the accelerated titration method (i.e. after the first dose levels in group 1 case subjects, when the subjects to 28 days after complete treatment of safety assessment, if not present dose limiting toxicity (DLT), increasing the dose to the next dose levels; Otherwise the study will be terminated . Study treatment name:EXG001-307 injection; Dosage form: injection; frequency and duration: single dose

Drug: EXG001-307 injection

Interventions

EXG001-307 injection DRUG

Research process includes filter (subjects signed informed consent for screening period before the pretreatment to the hormone, the longest 28 days), treatment period (the subjects accept including single hormone pretreatment, the study drug infusion) hospitalization and observation and follow-up treatment period (subjects to the participants to 18 months, lost to follow-up, active exit research subjects, or death). Subjects qualified in the screening period entered the treatment period and received EXG001-307, and entered the follow-up period after hospitalization. At the end of the study visit (subject at 18 months of age), eligible subjects will be asked to transfer to the long-term follow-up study.

single Arm-experimental group

Eligibility Criteria

• Age: Up to 180 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• SMA was diagnosed by bilateral allele SMN1 mutation (deletion or point mutation) gene, and there were 2 copies of SMN2 gene.
• On the day of administration, the age of the subjects did not exceed the 180th day after birth.
• The clinical history and signs are consistent with the manifestations of type I SMA, that is, hypotonia, lagging development of motor function, poor head control, round shoulder posture and excessive joint activity.
• The legal guardian of the subject understands the purpose, possible risks and rights of the test, agrees the subject to participate in the test, completes all research steps, tests and visits, and voluntarily signs the informed consent.
• During the study period, according to the changes of the subject's condition, the subject's legal guardian was willing to carry out standard treatment requirements such as nasal feeding, noninvasive mechanical ventilation and expectoration machine according to the researcher's suggestions.

You may not qualify if:

• The gestational age at birth was less than 35 weeks (245 days).
• During the screening period, when the subjects were awake or asleep and did not receive any auxiliary oxygen supply or respiratory support, the blood oxygen saturation was less than 96%.
• Invasive ventilation or tracheotomy is required, or the current use of noninvasive ventilation support is ≥ 16 hours / day on average.
• According to the WHO child growth standard (who 2009), the weight is lower than the 3rd percentile by age.
• Before administration, if the subjects have not been vaccinated or delayed vaccination according to the national vaccination plan of the current month, it will significantly affect their safety according to the evaluation of the researcher and the medical manager of the project team;
• Active viral infections (including HIV, covid-19, seropositive for hepatitis B or C, torch virus, EBV virus and syphilis).
• Severe non respiratory diseases within 2 weeks before screening.
• Upper respiratory tract infection or lower respiratory tract infection within 4 weeks before screening.
• There are other severe infections or diseases.
• There are known heart diseases or ECG abnormalities with clinical significance.
• Known allergy to prednisolone, other glucocorticoids or their excipients.
• Receive immunosuppressive therapy (e.g. cyclosporin, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab) requiring preventive administration within 3 months before administration.
• Immunomodulatory drugs (such as thymosin, interferon, etc.) are being used to treat myopathy, neuritis and diabetes (such as immunosuppressive agents, glucocorticoids, insulin).
• Anti AAV9 antibody titer \> 1:50 (determined by ELISA). If the potential subject's anti AAV9 antibody titer \> 1:50, it can be retested during the screening period. When the anti AAV9 antibody titer is ≤ 1:50, it can continue to participate in the screening.
• Abnormal laboratory test values with clinical significance (GGT, ALT and AST \> 2.5) × ULN, bilirubin ≥ 3.0 mg / dl, creatinine ≥ 1.0 mg / dl, hemoglobin \< 8 or \> 18 g / dl; Leukocyte count \> 20000 / cm3; Platelet count \< 100000 / cm3).

Sponsors & Collaborators

• Hangzhou Jiayin Biotech Ltd: lead

Study Sites (1)

Hangzhou Jiayin Biotechnology Co., Ltd

Hangzhou, Zhejiang, 310000, China

Location

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 Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2024
• First Posted: August 28, 2024
• Study Start: January 21, 2022
• Primary Completion: September 21, 2023
• Study Completion: January 21, 2024
• Last Updated: August 28, 2024

Record last verified: 2024-08

Locations

CN (1)