Autologous Stem Cell Transplantation of Cells Engineered to Express Alpha-Galactosidase A in Patients With Fabry Disease

April 16, 2024 updated by: University Health Network, Toronto

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
5

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada
        • Alberta Children's Hospital, University of Calgary
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
        • QE II Health Sciences Centre
    • Ontario
      • Toronto, Ontario, Canada
        • Princess Margaret Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment Arm
Patients will receive Health Canada approved transduced autologous CD34+ cell product.
Biological: Lentivirus Alpha-gal A transduced stem cells

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
5 years
Gb3 levels
Time Frame: 5 years
Reduction of Gb3 in plasma and urine
5 years
lyso-Gb3 levels
Time Frame: 5 years
Reduction of lyso-Gb3 in plasma and urine
5 years
lyso-Gb3 analogue (-28)
Time Frame: 5 years
Reduction of lyso-Gb3 (-28) in plasma and urine
5 years
lyso-Gb3 analogue (-2)
Time Frame: 5 years
Reduction of lyso-Gb3 (-2) in plasma and urine
5 years
lyso-Gb3 analogue (+16)
Time Frame: 5 years
Reduction of lyso-Gb3 (+16) in plasma and urine
5 years
lyso-Gb3 analogue (+34)
Time Frame: 5 years
Reduction of lyso-Gb3 (+34) in plasma and urine
5 years
lyso-Gb3 analogue (+50)
Time Frame: 5 years
Reduction of lyso-Gb3 (+50) in plasma and urine
5 years
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
5 years
transduction efficiency
Time Frame: 5 years
Vector copy number per genome on the CD34+ cell population
5 years
transduction efficiency
Time Frame: 5 years
Number of colonies positive by PCR for the provirus out of number plated in the colony assay
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Health Network, Toronto

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Ozmosis Research Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 15, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 9, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 15, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 17, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 16, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • OZM-074

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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