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Trial record 1 of 2 for:    fabry cd34
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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
Sponsor:
Collaborator:
Ozmosis Research Inc.
Information provided by (Responsible Party):
University Health Network, Toronto

Study Description
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Brief Summary:
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 or disease Intervention/treatment Phase
Fabry Disease Biological: Lentivirus Alpha-gal A transduced stem cells Phase 1

Study Design
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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

Resource links provided by the National Library of Medicine


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


Outcome Measures
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Primary Outcome Measures :
  1. 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 :
  1. 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.

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

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

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

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

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

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

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

  9. 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

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

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


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

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
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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): NCT02800070


Locations
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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
Sponsors and Collaborators
University Health Network, Toronto
Ozmosis Research Inc.
More Information
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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
Keywords provided by University Health Network, Toronto:
autologous stem cell transplant
gene therapy
Fabry disease
lentivirus
haematopoietic stem cell transplant
Additional relevant MeSH terms:
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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