Autologous Stem Cell Transplantation of Cells Engineered to Express Alpha-Galactosidase A in Patients With Fabry Disease
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ClinicalTrials.gov Identifier: NCT02800070 |
Recruitment Status :
Active, not recruiting
First Posted : June 15, 2016
Last Update Posted : April 22, 2020
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Condition or disease | Intervention/treatment | Phase |
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Fabry Disease | Biological: Lentivirus Alpha-gal A transduced stem cells | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 5 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (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 |
Study Start Date : | July 2016 |
Estimated Primary Completion Date : | February 2024 |
Estimated Study Completion Date : | February 2024 |

Arm | Intervention/treatment |
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Experimental: Treatment Arm
Patients will receive Health Canada approved transduced autologous CD34+ cell product.
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Biological: Lentivirus Alpha-gal A transduced stem cells |
- 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.
- 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

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, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 50 Years (Adult) |
Sexes Eligible for Study: | Male |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Male patients 18-50 years of age at the time of enrollment
- Diagnosis of Fabry disease (FD) as defined by very low or absent α-gal A activity
- Classic FD Type I phenotype with alpha-galactosidase A (GLA) genotyping
- Patients on enzyme replacement therapy (ERT) prior to enrollment
- Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
- Adequate organ function within 21 days prior to Pre-Treatment Phase:
- Willing and capable of signing and giving written informed consent in accordance with Research Ethics Board (REB) requirements
- 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
- 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.
- 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:
- Males with variant Fabry Disease.
- Female gender
- Use of immunosuppressive agents or any anticoagulant
- Ongoing ERT-related infusion associated reactions of moderate-to-severe intensity
- Presence of anti-agalsidase immunoglobulin (Ig)G antibodies above a threshold (5-fold above normal;) or evidence of high titre neutralizing antibodies
- 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).
- Uncontrolled bacterial, viral, or fungal infections
- Prior malignancies except resected basal cell carcinoma
- Chronic Kidney Disease (CKD) stage >2
- History of heart failure or left ventricle ejection fraction (LVEF) <45% or moderate to severe diastolic dysfunction by standard criteria
- Arrhythmia: bundle branch block, heart block degree II or III, atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, cardiac arrest, pacemaker, implantable cardiac defibrillator
- 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
- Uncontrolled hypertension
- Diabetes mellitus
- Advanced liver disease, liver failure, cirrhosis
- Immune deficiency state
- Moderate-to-severe chronic obstructive pulmonary disease (COPD)
- Any hematological condition with white blood cells (WBC) <3.0 x109/L, platelet count <100 x109/L, and/or hemoglobin <100 g/L
- Prior bone marrow transplant (BMT) or organ transplant
- Any condition that would preclude use of Melphalan
- Use of a drug with cytotoxic or immunosuppressive effect within 60 days of trial entry
- Uncontrolled psychiatric disorder
- Active chronic infection
- Prior tuberculosis
- Any other serious concurrent disease
- Cognitive impairment that would prevent informed consent
- Use of an investigational drug within 30 days of stem cell transplant (SCT)

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): NCT02800070
Canada, Alberta | |
Alberta Children's Hospital, University of Calgary | |
Calgary, Alberta, Canada | |
Canada, Nova Scotia | |
QE II Health Sciences Centre | |
Halifax, Nova Scotia, Canada | |
Canada, Ontario | |
Princess Margaret Cancer Centre | |
Toronto, Ontario, Canada |
Responsible Party: | University Health Network, Toronto |
ClinicalTrials.gov Identifier: | NCT02800070 |
Other Study ID Numbers: |
OZM-074 |
First Posted: | June 15, 2016 Key Record Dates |
Last Update Posted: | April 22, 2020 |
Last Verified: | April 2020 |
autologous stem cell transplant gene therapy Fabry disease lentivirus haematopoietic stem cell transplant |
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 |