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AzTrials

Fabry DiseasePhase 1NCT02800070

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

A Phase 1 study testing Lentivirus Alpha-gal A transduced stem cells in people with Fabry Disease, run by University Health Network, Toronto at 3 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 50 years, men only
Conditions the study is for
Fabry Disease
What is being tested?
Lentivirus Alpha-gal A transduced stem cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
3 sitesCanada
Study dates
Jul 2016to Apr 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • Men only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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).
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  • 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)

Trial locations and contacts

3 sites in 1 country.

Canada3 sites

  • Alberta Children's Hospital, University of Calgary

    Calgary, Alberta

  • QE II Health Sciences Centre

    Halifax, Nova Scotia

  • Princess Margaret Cancer Centre

    Toronto, Ontario

Other trials in Canada

About this study

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

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.

Conditions
Fabry Disease
Being tested
Lentivirus Alpha-gal A transduced stem cells
Keywords
autologous stem cell transplant, gene therapy, Fabry disease, lentivirus, haematopoietic stem cell transplant
Medical subject headings
Fabry Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lentivirus Alpha-gal A transduced stem cellsBiological

Study groups in NCT02800070
Study groupRoleWhat they receive
Treatment ArmExperimentalPatients will receive Health Canada approved transduced autologous CD34+ cell product.
Receives: Biological: Lentivirus Alpha-gal A transduced stem cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

    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.

    Measured: 5 years

Secondary outcomes (11)

  1. Alpha-gal A enzyme activity levels

    Increase in α-gal A enzyme activity within the plasma, leukocytes, and Bone marrow aspirate.

    Measured: 5 years

  2. Gb3 levels

    Reduction of Gb3 in plasma and urine

    Measured: 5 years

  3. lyso-Gb3 levels

    Reduction of lyso-Gb3 in plasma and urine

    Measured: 5 years

  4. lyso-Gb3 analogue (-28)

    Reduction of lyso-Gb3 (-28) in plasma and urine

    Measured: 5 years

  5. lyso-Gb3 analogue (-2)

    Reduction of lyso-Gb3 (-2) in plasma and urine

    Measured: 5 years

  6. lyso-Gb3 analogue (+16)

    Reduction of lyso-Gb3 (+16) in plasma and urine

    Measured: 5 years

  7. lyso-Gb3 analogue (+34)

    Reduction of lyso-Gb3 (+34) in plasma and urine

    Measured: 5 years

  8. lyso-Gb3 analogue (+50)

    Reduction of lyso-Gb3 (+50) in plasma and urine

    Measured: 5 years

  9. vector copy number per genome on the CD34+ cell population

    Persistence of LV-transduced cells as measured by quantitative (q)PCR

    Measured: 5 years

  10. transduction efficiency

    Vector copy number per genome on the CD34+ cell population

    Measured: 5 years

  11. transduction efficiency

    Number of colonies positive by PCR for the provirus out of number plated in the colony assay

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2016 (estimated)
  2. Study startJul 2016
  3. Primary completionApr 2024
  4. Study completionApr 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02800070
Sponsor's protocol ID
OZM-074
Status last verified
Apr 2024
First submitted
15 Apr 2016
Last updated
17 Apr 2024
Results posted
No
Data monitoring committee
Yes

Publications

  • Khan A, Barber DL, Huang J, Rupar CA, Rip JW, Auray-Blais C, Boutin M, O'Hoski P, Gargulak K, McKillop WM, Fraser G, Wasim S, LeMoine K, Jelinski S, Chaudhry A, Prokopishyn N, Morel CF, Couban S, Duggan PR, Fowler DH, Keating A, West ML, Foley R, Medin JA. Lentivirus-mediated gene therapy for Fabry disease. Nat Commun. 2021 Feb 25;12(1):1178. doi: 10.1038/s41467-021-21371-5.

    PubMed 33633114

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lentivirus Alpha-gal A transduced stem cells in people with Fabry Disease, run by University Health Network, Toronto at 3 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02800070, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2024.

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