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Trial record 1 of 1 for:    NCT02800070
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Autologous Stem Cell Transplantation of Cells Engineered to Express Alpha-Galactosidase A in Patients With Fabry Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by University Health Network, Toronto
Ozmosis Research Inc.
Information provided by (Responsible Party):
University Health Network, Toronto Identifier:
First received: April 15, 2016
Last updated: August 16, 2016
Last verified: August 2016
This is a first-in-human study for the treatment of Fabry disease. Eligible patients will have an autologous stem cell transplantation using CD34+ cells that are transduced with the lentivirus vector containing the human alpha-gal A gene. The researchers of this study would like to see if the re-introduction of transduced cells will help increase the levels of alpha-gal A enzyme levels and to determine the safety and toxicity of autologous stem cell transplantation using CD34+ cells transduced with lentivirus vector containing the alpha-gal A gene. This study's objective is to determine the safety and toxicity of lentivirus alpha-gal A transduced CD34+ cells in adult males with Fabry disease.

Condition Intervention Phase
Fabry Disease
Biological: Lentivirus Alpha-gal A transduced stem cells
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical Pilot Study of Autologous Stem Cell Transplantation of Cluster of Differentiation 34 Positive (CD34+) Cells Engineered to Express Alpha-Galactosidase A in Patients With Fabry Disease

Resource links provided by NLM:

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment [ Time Frame: 5 years ]
    Safety measurement will be based on all clinical and laboratory assessment post-baseline. The assessment will be the frequency of clinically notable abnormal vital signs and laboratory values, and the frequency of treatment-related adverse events.

Secondary Outcome Measures:
  • Alpha-gal A enzyme activity levels [ Time Frame: 5 years ]
    Increase in α-gal A enzyme activity within the plasma, leukocytes, and Bone marrow aspirate.

  • Gb3 levels [ Time Frame: 5 years ]
    Reduction of Gb3 in plasma and urine

  • lyso-Gb3 levels [ Time Frame: 5 years ]
    Reduction of lyso-Gb3 in plasma and urine

  • lyso-Gb3 analogue (-28) [ Time Frame: 5 years ]
    Reduction of lyso-Gb3 (-28) in plasma and urine

  • lyso-Gb3 analogue (-2) [ Time Frame: 5 years ]
    Reduction of lyso-Gb3 (-2) in plasma and urine

  • lyso-Gb3 analogue (+16) [ Time Frame: 5 years ]
    Reduction of lyso-Gb3 (+16) in plasma and urine

  • lyso-Gb3 analogue (+34) [ Time Frame: 5 years ]
    Reduction of lyso-Gb3 (+34) in plasma and urine

  • lyso-Gb3 analogue (+50) [ Time Frame: 5 years ]
    Reduction of lyso-Gb3 (+50) in plasma and urine

  • vector copy number per genome on the CD34+ cell population [ Time Frame: 5 years ]
    Persistence of LV-transduced cells as measured by quantitative (q)PCR

  • transduction efficiency [ Time Frame: 5 years ]
    Vector copy number per genome on the CD34+ cell population

  • transduction efficiency [ Time Frame: 5 years ]
    Number of colonies positive by PCR for the provirus out of number plated in the colony assay

Estimated Enrollment: 6
Study Start Date: July 2016
Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm
Patients will receive Health Canada approved transduced autologous CD34+ cell product.
Biological: Lentivirus Alpha-gal A transduced stem cells


Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male patients 18-50 years of age at the time of enrollment
  2. Diagnosis of Fabry disease (FD) as defined by very low or absent α-gal A activity
  3. Classic FD Type I phenotype with alpha-galactosidase A (GLA) genotyping
  4. Patients on enzyme replacement therapy (ERT) prior to enrollment
  5. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
  6. Adequate organ function within 21 days prior to Pre-Treatment Phase:
  7. Willing and capable of signing and giving written informed consent in accordance with Research Ethics Board (REB) requirements
  8. Willing to comply with all procedures outlined in the study protocol, cooperative with the protocol schedule, able to return for safety evaluation, or otherwise likely to complete the study
  9. Willing to abstain from sexual activity or willing to use condoms during sexual intercourse from day of Melphalan administration on day -1 of Phase 3 until after 12 months follow-up post-transplant.
  10. Willing to not donate sperm after receiving Melphalan. Sperm banking will be recommended to any patient who would like to father children in the future.

Exclusion Criteria:

  1. Males with variant Fabry Disease.
  2. Female gender
  3. Use of immunosuppressive agents or any anticoagulant
  4. Ongoing ERT-related infusion associated reactions of moderate-to-severe intensity
  5. Presence of anti-agalsidase immunoglobulin (Ig)G antibodies above a threshold (5-fold above normal;) or evidence of high titre neutralizing antibodies
  6. Blood test positive for Hepatitis B virus (HBV), Hepatitis C virus (HCV), human immunodeficiency virus (HIV), human T-cell lymphotropic virus type 1 (HTLV-1), human T-cell lymphotropic virus type 1 (HTLV-2), or Venereal Disease Research Laboratory test (VDRL; Transmissible Disease (TD) testing will be done in Pre-Treatment Phase 2 - see section 5.1 for full panel of TD tests. Patients will only be excluded from the study if positive for the TD tests listed here in this exclusion).
  7. Uncontrolled bacterial, viral, or fungal infections
  8. Prior malignancies except resected basal cell carcinoma
  9. Chronic Kidney Disease (CKD) stage >2
  10. History of heart failure or left ventricle ejection fraction (LVEF) <45% or moderate to severe diastolic dysfunction by standard criteria
  11. Arrhythmia: bundle branch block, heart block degree II or III, atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, cardiac arrest, pacemaker, implantable cardiac defibrillator
  12. Coronary artery disease with angina, prior myocardial infarction, percutaneous transluminal coronary angioplasty with or without stent, coronary artery bypass graft surgery, moderate to severe valvular heart disease, valve replacement surgery
  13. Uncontrolled hypertension
  14. Diabetes mellitus
  15. Advanced liver disease, liver failure, cirrhosis
  16. Immune deficiency state
  17. Moderate-to-severe chronic obstructive pulmonary disease (COPD)
  18. Any hematological condition with white blood cells (WBC) <3.0 x109/L, platelet count <100 x109/L, and/or hemoglobin <100 g/L
  19. Prior bone marrow transplant (BMT) or organ transplant
  20. Any condition that would preclude use of Melphalan
  21. Use of a drug with cytotoxic or immunosuppressive effect within 60 days of trial entry
  22. Uncontrolled psychiatric disorder
  23. Active chronic infection
  24. Prior tuberculosis
  25. Any other serious concurrent disease
  26. Cognitive impairment that would prevent informed consent
  27. Use of an investigational drug within 30 days of stem cell transplant (SCT)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02800070

Contact: Jeffrey Medin

Canada, Alberta
Alberta Children's Hospital, University of Calgary Recruiting
Calgary, Alberta, Canada
Contact: Aneal Khan   
Contact: Andrew Daly   
Canada, Nova Scotia
QE II Health Sciences Centre Not yet recruiting
Halifax, Nova Scotia, Canada
Contact: MIchael West   
Contact: Stephen Couban   
Canada, Ontario
Princess Margaret Cancer Centre Not yet recruiting
Toronto, Ontario, Canada
Contact: Armand Keating   
Contact: Chantal Morel   
Sponsors and Collaborators
University Health Network, Toronto
Ozmosis Research Inc.
  More Information

Responsible Party: University Health Network, Toronto Identifier: NCT02800070     History of Changes
Other Study ID Numbers: OZM-074
Study First Received: April 15, 2016
Last Updated: August 16, 2016

Keywords provided by University Health Network, Toronto:
autologous stem cell transplant
gene therapy
Fabry disease
haematopoietic stem cell transplant

Additional relevant MeSH terms:
Fabry Disease
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
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders processed this record on May 24, 2017