NCT05815004

An Efficacy and Safety Study of AVR-RD-02 Compared to Enzyme Replacement Therapy for Treatment of Gaucher Disease Type 3

Guard3: An Open-label, Parallel-arm, Randomized, Controlled, Phase 2/Phase 3 Study Evaluating the Efficacy and Safety of Autologous HSC Gene Therapy, AVR-RD-02, Compared to ERT for Gaucher Disease Type 3 in Participants Aged 2 to 25

• Status: Withdrawn
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: AVROBIO · Industry
• Sex: All
• Age: 2 Years – 25 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the efficacy and safety of autologous hemotopoietic stem cell (HSC) gene therapy, AVR-RD-02, compared to enzyme replacement therapy, for the treatment of Gaucher disease Type 3 in male and female participants aged 2 to 25 years. The study will consist of 2 parts - Core (Part 1) followed by the ERT-crossover (Part 2)

Detailed description

Core (Part 1) Once a participant consents, he/she will complete the screening period within 30 days. Eligible participants will have baseline assessments completed 30 days later and then will be randomized into one of two treatment arms: AVR-RD-02 arm or ERT control arm. If randomized to the AVR-RD-02 arm, the participant will enter the pre-gene therapy infusion period (approximately 15 weeks), which consists of mobilization, apheresis, AVR-RD-02 preparation and testing for release, discontinuation of ERT, and conditioning. The participant will then receive the AVR-RD-02 gene therapy (1 day) followed by a 52-week follow-up period in which periodic safety and efficacy assessments will be performed. Participants will not receive ERT after gene therapy infusion unless indicated by pre-specified laboratory and clinical criteria. If randomized to the ERT Control arm, the participant will remain on their prescribed ERT regimen for 52-week observation period with approximately 4 study visits during this time. ERT-crossover (Part 2) After 52 weeks of observation in Part 1, participants in the ERT Control Arm will have the opportunity to enter Part 2 and receive AVR-RD-02. They will start with baseline assessments and follow a similar schedule to the schedule followed by participants assigned to AVR-RD-02 in the Core Study (Part 1).

Conditions

• Gaucher Disease, Type 3

Interventions

Type	Name	Description
DRUG	Gene therapy	AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase)
DRUG	Enzyme Replacement Agent	A hydrolytic lysosomal glucocerebrosidase-specific enzyme

Timeline

• Start date: 2023-10-01
• Primary completion: 2027-12-01
• Completion: 2027-12-01
• First posted: 2023-04-18
• Last updated: 2023-08-09

Regulatory

• FDA-regulated drug study