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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03454893




Registration number
NCT03454893
Ethics application status
Date submitted
20/12/2017
Date registered
6/03/2018

Titles & IDs
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
Secondary ID [1] 0 0
AVRO-RD-01-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fabry Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AVR-RD-01

Experimental: Single Assignment AVR-RD-01 - AVR-RD-01 is an autologous CD34+-enriched cell fraction transduced with LV/AGA containing an RNA transcript that, after reverse transcription, results in codon-optimized cDNA that, upon its integration into the human genome, encodes for functional human AGA.


Treatment: Drugs: AVR-RD-01
Single IV infusion of between 3 - 20 x 10\^6 CD34+ cells/kg.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Baseline to Week 48 post gene therapy
Primary outcome [2] 0 0
Change From Baseline in Immunogenicity of AVR-RD-01
Timepoint [2] 0 0
Baseline to Week 48 post gene therapy
Primary outcome [3] 0 0
Presence of Replication Competent Lentivirus (RCL)
Timepoint [3] 0 0
Baseline to Week 48 post gene therapy
Primary outcome [4] 0 0
Evaluation of Aberrant Clonal Expansion
Timepoint [4] 0 0
Baseline to Week 48 post gene therapy
Primary outcome [5] 0 0
Change From Baseline in the Average Number of Gb3 Inclusions (ie, Myelinosomes) Per Kidney Peritubular Capillary (PTC) Per Subject
Timepoint [5] 0 0
Baseline to Week 48 post gene therapy
Secondary outcome [1] 0 0
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)
Timepoint [1] 0 0
At Week 24 and Week 48 post gene therapy
Secondary outcome [2] 0 0
Change From Baseline (CFB) in AGA Enzyme Activity Level in Plasma and Peripheral Blood Leukocytes (PBLs)
Timepoint [2] 0 0
Baseline to Week 24 and Week 48 post gene therapy
Secondary outcome [3] 0 0
Change From Baseline in Globotriaosylceramide (Gb3) Biomarkers for Fabry Disease in Plasma
Timepoint [3] 0 0
Baseline to Week 24 and Week 48 post gene therapy
Secondary outcome [4] 0 0
Change From Baseline in Globotriaosylceramide (Gb3) Biomarkers for Fabry Disease in Urine
Timepoint [4] 0 0
Baseline to Week 24 and Week 48 post gene therapy
Secondary outcome [5] 0 0
Change From Baseline in Substrate (i.e. Gb3) in Skin Biopsy
Timepoint [5] 0 0
Baseline to Week 24 and Week 48 post gene therapy
Secondary outcome [6] 0 0
Change From Baseline in Renal Function as Assessed by Measured Glomerular Filtration Rate (mGFR)
Timepoint [6] 0 0
Baseline to Week 48 post gene therapy
Secondary outcome [7] 0 0
Change From Baseline in Renal Function as Assessed by Estimated Glomerular Filtration Rate (eGFR)
Timepoint [7] 0 0
Baseline to Week 24 and Week 48 post gene therapy
Secondary outcome [8] 0 0
Change From Baseline in Renal Function as Assessed by Urine Total Protein Levels
Timepoint [8] 0 0
Baseline to Week 24 and Week 48 post gene therapy
Secondary outcome [9] 0 0
Change From Baseline in Renal Function as Assessed by Urine Albumin Levels
Timepoint [9] 0 0
Baseline to Week 24 and Week 48 post gene therapy
Secondary outcome [10] 0 0
Change From Baseline in Left Ventricular Mass Index (LVMI) as Assessed by Cardiac Magnetic Resonance Imaging (MRI)
Timepoint [10] 0 0
Baseline to Week 48 post gene therapy
Secondary outcome [11] 0 0
Change From Baseline in Abdominal Pain and Stool Consistency as Assessed by the Diary for Irritable Bowel Syndrome Symptoms-Diarrhea (DIBSS-D)
Timepoint [11] 0 0
Baseline to Week 24 and Week 48 post gene therapy
Secondary outcome [12] 0 0
Change From Baseline in Brief Pain Inventory-Short Form (BPI-SF) Questionnaire Scores
Timepoint [12] 0 0
Baseline to Week 24 and Week 48 post gene therapy
Secondary outcome [13] 0 0
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
Timepoint [13] 0 0
Baseline to Week 48 post gene therapy
Secondary outcome [14] 0 0
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)
Timepoint [14] 0 0
At Week 48 post gene therapy

Eligibility
Key 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).
Minimum age
16 Years
Maximum age
50 Years
Sex
Males
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/02/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/03/2022
Sample size
Target
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
Parkville VI
Recruitment hospital [1] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [2] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment postcode(s) [2] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
United States of America
State/province [2] 0 0
Pennsylvania
Country [3] 0 0
Brazil
State/province [3] 0 0
Rio Grande Do Sul

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AVROBIO
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Inderpal Panesar, MRPharmS
Address 0 0
AVROBIO, Inc
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03454893