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

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ClinicalTrials.gov Identifier: NCT03454893
Recruitment Status : Recruiting
First Posted : March 6, 2018
Last Update Posted : March 19, 2018
Sponsor:
Information provided by (Responsible Party):
AvroBio

Brief Summary:
This is a multinational, open-label study to assess the efficacy and safety of AVR-RD-01 in approximately 8 to 12 male subjects 16 years of age or older and postpubertal with a confirmed diagnosis of classic Fabry disease based on deficient AGA enzyme activity who have not previously received treatment with enzyme replacement therapy (ERT) and/or chaperone therapy at the time of Screening.

Condition or disease Intervention/treatment Phase
Fabry Disease Drug: AVR-RD-01 Phase 1 Phase 2

Detailed Description:

The duration of each subject's participation in this study will be approximately 58 weeks (or 1 year, 6 weeks), comprised of a five study periods (Screening, Baseline, Pre-transplant, Transplant, and Post-transplant Follow-up). During the Screening Period (approximately 4 weeks), written informed consent (and assent, if applicable) will be obtained and the subject will complete other Screening procedures to confirm study eligibility. Once study eligibility is confirmed, subjects will enter the Baseline Period (up to 3 days) during which time assessments will be performed to establish a pre-transplant baseline. Once baseline assessments are complete, the subject will enter the Pre-transplant Period (approximately 6 weeks) during which time mobilization, apheresis, AVR-RD-01 drug product preparation and testing for release, and conditioning regimen administration to achieve partial myeloablation will take place. Following completion of the Pre-transplant Period, the subject will enter the Transplant Period (1 day) during which time AVR-RD-01 infusion will take place. After AVR-RD-01 infusion, the subject will enter the Post-transplant Follow-up Period (approximately 48 weeks), during which time periodic safety and efficacy assessments will be performed to assess measures of engraftment, clinical response, and safety post-transplant. Post-transplant follow-up will occur at the following time points: Week 1 (Days 1 through 7), Week 2 (Days 10 and 14), Week 4 (Day 28), Week 8 (Day 56), Week 12 (Day 84), Week 24 (Day 168), Week 36 (Day 216), and Week 48 (Day 336).

After study completion, consenting subjects will continue periodic safety and efficacy assessments for approximately 14 years (for a total of 15 years post-transplant follow-up) in a long-term follow-up study to AVRO-RD-01-201.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : February 21, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Single Assignment AVR-RD-01
AVR-RD-01 Drug Product (autologous CD34+ cell-enriched fraction that contains cells transduced with Lentiviral Vector/alpha-galactosidase A (AGA) encoding for the human AGA complementary deoxyribonucleic acid (cDNA) sequence
Drug: AVR-RD-01
AVR-RD-01 Drug Product (autologous CD34+ cell-enriched fraction that contains cells transduced with Lentiviral Vector/alpha-galactosidase A (AGA) encoding for the human AGA complementary deoxyribonucleic acid (cDNA) sequence




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events of AVR-RD-01 drug product [ Time Frame: baseline to 48 weeks post gene therapy ]
    Incidence and severity of adverse events and serious adverse events



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject is male, 16 years of age or older, and postpubertal,,
  2. Subject has a confirmed diagnosis of classic Fabry disease based on deficient AGA enzyme activity (defined as < 1% of normal).
  3. Subject has a history of GI symptoms including abdominal pain and diarrhea.

Exclusion Criteria:

  1. Subject has previously received ERT and/or chaperone therapy at any time for treatment of Fabry disease.
  2. Subject has eGFR < 60 mL/min/1.73 m² (ie, chronic kidney disease [CKD] stage ≥ 3) at Screening.
  3. Subject has a prior history of myocardial infarction (MI).
  4. Subject has 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).
  5. Subject has a history of moderate to severe valvular heart disease requiring valve replacement.
  6. Subject has 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.
  7. Subject has a history of clinically significant cardiac arrhythmia (eg, heart block [second or third degree], atrial fibrillation requiring therapy (history of intermittent atrial fibrillation not requiring treatment is allowed), ventricular fibrillation, ventricular tachycardia, supraventricular tachycardia, or cardiac arrest).
  8. Subject has a prior history of stroke and/or transient ischemic attack (TIA).
  9. Subject has aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≥ 3 times the upper limit of normal (ULN) at Screening.
  10. Subject has a prior history of (or current) malignancy; the one exception is a prior history of resected basal cell carcinoma.
  11. Subject has previously received treatment with AVR-RD-01 or any other gene therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03454893


Contacts
Contact: lisamarie fahy 6179148417 lisamarie.fahy@avrobio.com

Locations
Australia, Parkville VIC
Royal Melbourne Hospital Recruiting
Melbourne, Parkville VIC, Australia
Contact: Richard Verelli    61 3 9342 7348    Richard.verrelli@mh.org.au   
Principal Investigator: Kathy Nichols, MD         
Australia
Royal Perth Hospital Recruiting
Perth, Australia
Contact: David Nolan    +61 8 9224 3771    EHMS.REG@health.wa.gov.au   
Principal Investigator: Mark Thomas, MD         
Sponsors and Collaborators
AvroBio
Investigators
Study Director: Nerissa Kreher, MD AvroBio

Responsible Party: AvroBio
ClinicalTrials.gov Identifier: NCT03454893     History of Changes
Other Study ID Numbers: AVRO-RD-01-201
First Posted: March 6, 2018    Key Record Dates
Last Update Posted: March 19, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Fabry Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders