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

• Register: ClinicalTrials.gov
• Last refreshed on: 8 January 2024
• Main ID: NCT02800070
• Date of registration: 15/04/2016
• Prospective Registration: Yes
• Primary sponsor: University Health Network, Toronto
• Public title: Autologous Stem Cell Transplantation of Cells Engineered to Express Alpha-Galactosidase A in Patients With Fabry Disease
• Scientific 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
• Date of first enrolment: July 2016
• Target sample size: 5
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02800070
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Canada

Key inclusion & exclusion 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 a-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)



Age minimum: 18 Years
Age maximum: 50 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Fabry Disease

Intervention(s)

Biological: Lentivirus Alpha-gal A transduced stem cells

Primary Outcome(s)

Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment [Time Frame: 5 years]

Secondary Outcome(s)

Gb3 levels [Time Frame: 5 years]

lyso-Gb3 analogue (+50) [Time Frame: 5 years]

Alpha-gal A enzyme activity levels [Time Frame: 5 years]

lyso-Gb3 analogue (+16) [Time Frame: 5 years]

lyso-Gb3 analogue (-2) [Time Frame: 5 years]

lyso-Gb3 analogue (-28) [Time Frame: 5 years]

transduction efficiency [Time Frame: 5 years]

lyso-Gb3 analogue (+34) [Time Frame: 5 years]

lyso-Gb3 levels [Time Frame: 5 years]

vector copy number per genome on the CD34+ cell population [Time Frame: 5 years]

Secondary ID(s)

OZM-074

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Ozmosis Research Inc.