Open Label, Study Of Efficacy and Safety Of AVR-RD-01 for Treatment-Naive Subjects With Classic Fabry Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 15 January 2024
• Main ID: NCT03454893
• Date of registration: 20/12/2017
• Prospective Registration: Yes
• Primary sponsor: AVROBIO
• Public title: Open Label, Study Of Efficacy and Safety Of AVR-RD-01 for Treatment-Naive Subjects With Classic Fabry Disease
• Scientific title: An Open-Label, Multinational Study Of The Efficacy And Safety of Ex Vivo, Lentiviral Vector-Mediated Gene Therapy AVR-RD-01 For Treatment-Naive Subjects With Classic Fabry Disease
• Date of first enrolment: February 21, 2018
• Target sample size: 15
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT03454893
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Australia, Brazil, Canada, United States

Contacts

• Name: Inderpal Panesar, MRPharmS
• Affiliation: AVROBIO, Inc

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Subject was male, 16 years of age or older (18 years of age or older in the US), and
post pubertal,(minimum age by region)

2. Subject had a confirmed diagnosis of classic Fabry disease based on deficient AGA
enzyme activity (defined as < 1% of normal).

Exclusion Criteria:

1. Subject had a galactosidase alpha (GLA) gene mutation associated with late-onset
cardiac variant Fabry disease.

2. Subject had previously received ERT and/or chaperone therapy within 3 years for
treatment of Fabry disease.

3. Subject had tested positive for anti-AGA antibodies at the time of screening.

4. Subject had eGFR < 60 mL/min/1.73 m² (ie, chronic kidney disease [CKD] stage = 3) at
Screening.

5. Subject had a prior history of myocardial infarction (MI).

6. Subject had a history of coronary artery disease (CAD) with angina requiring
percutaneous transluminal coronary angioplasty (with or without stent placement)
and/or coronary artery bypass graft (CABG).

7. Subject had a history of moderate to severe valvular heart disease requiring valve
replacement.

8. Subject had a history of heart failure, moderate to severe diastolic dysfunction,
and/or left ventricular ejection fraction (LVEF) = 45% on echocardiogram (ECHO)
performed at rest at Screening.

9. Subject had a history of clinically significant cardiac arrhythmia (eg, heart block
[second or third degree], atrial fibrillation requiring therapy, ventricular
fibrillation, ventricular tachycardia, supraventricular tachycardia, or cardiac
arrest).

Note [history of intermittent atrial fibrillation not requiring treatment was
allowed].

10. Subject had a prior history of stroke and/or transient ischemic attack (TIA).

11. Subject had aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) = 3
times the upper limit of normal (ULN) at Screening.

12. Subject had a prior history of (or current) malignancy; the one exception is a prior
history of resected basal cell carcinoma.

13. Subject had previously received treatment with AVR-RD-01 or any other gene therapy.

Other inclusion/exclusion criteria apply.



Age minimum: 16 Years
Age maximum: 50 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Fabry Disease

Intervention(s)

Drug: AVR-RD-01

Primary Outcome(s)

Evaluation of Aberrant Clonal Expansion [Time Frame: Baseline to Week 48 post gene therapy]

Incidence of and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Baseline to Week 48 post gene therapy]

Change From Baseline in Immunogenicity of AVR-RD-01 [Time Frame: Baseline to Week 48 post gene therapy]

Change From Baseline in the Average Number of Gb3 Inclusions (ie, Myelinosomes) Per Kidney Peritubular Capillary (PTC) Per Subject [Time Frame: Baseline to Week 48 post gene therapy]

Presence of Replication Competent Lentivirus (RCL) [Time Frame: Baseline to Week 48 post gene therapy]

Secondary Outcome(s)

Change From Baseline in Brief Pain Inventory-Short Form (BPI-SF) Questionnaire Scores [Time Frame: Baseline to Week 24 and Week 48 post gene therapy]

Change From Baseline in Left Ventricular Mass Index (LVMI) as Assessed by Cardiac Magnetic Resonance Imaging (MRI) [Time Frame: Baseline to Week 48 post gene therapy]

Average Vector Copy Number (VCN) in Peripheral Blood Leukocytes as Assessed by Quantitative Polymerase Chain Reaction (qPCR) and/or Droplet Digital Polymerase Chain Reaction (ddPCR) [Time Frame: At Week 24 and Week 48 post gene therapy]

Change From Baseline in Renal Function as Assessed by Measured Glomerular Filtration Rate (mGFR) [Time Frame: Baseline to Week 48 post gene therapy]

Change From Baseline in Renal Function as Assessed by Estimated Glomerular Filtration Rate (eGFR) [Time Frame: Baseline to Week 24 and Week 48 post gene therapy]

Change From Baseline in Renal Function as Assessed by Urine Albumin Levels [Time Frame: Baseline to Week 24 and Week 48 post gene therapy]

Change From Baseline in Abdominal Pain and Stool Consistency as Assessed by the Diary for Irritable Bowel Syndrome Symptoms-Diarrhea (DIBSS-D) [Time Frame: Baseline to Week 24 and Week 48 post gene therapy]

Change From Baseline in Globotriaosylceramide (Gb3) Biomarkers for Fabry Disease in Plasma [Time Frame: Baseline to Week 24 and Week 48 post gene therapy]

Change From Baseline in Globotriaosylceramide (Gb3) Biomarkers for Fabry Disease in Urine [Time Frame: Baseline to Week 24 and Week 48 post gene therapy]

Change From Baseline in Renal Function as Assessed by Urine Total Protein Levels [Time Frame: Baseline to Week 24 and Week 48 post gene therapy]

Change From Baseline (CFB) in AGA Enzyme Activity Level in Plasma and Peripheral Blood Leukocytes (PBLs) [Time Frame: Baseline to Week 24 and Week 48 post gene therapy]

Change From Baseline in Physical and Mental Functioning as Assessed by the Short Form 36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores [Time Frame: Baseline to Week 48 post gene therapy]

Change From Baseline in Substrate (i.e. Gb3) in Skin Biopsy [Time Frame: Baseline to Week 24 and Week 48 post gene therapy]

Average Vector Copy Number (VCN) in Bone Marrow / Progenitor Cells as Assessed by Quantitative Polymerase Chain Reaction (qPCR) and/or Droplet Digital Polymerase Chain Reaction (ddPCR) [Time Frame: At Week 48 post gene therapy]

Secondary ID(s)

AVRO-RD-01-201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/01/2024
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03454893