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

NCT ID: NCT02800070

Last Updated: 2024-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2024-04-30

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.

Conditions

Fabry Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

Patients will receive Health Canada approved transduced autologous CD34+ cell product.

Group Type: EXPERIMENTAL

Lentivirus Alpha-gal A transduced stem cells

Intervention Type: BIOLOGICAL

Interventions

Lentivirus Alpha-gal A transduced stem cells

Intervention Type: BIOLOGICAL

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Ozmosis Research Inc.

INDUSTRY

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Alberta Children's Hospital, University of Calgary

Calgary, Alberta, Canada

QE II Health Sciences Centre

Halifax, Nova Scotia, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 33633114 (View on PubMed)

Other Identifiers

OZM-074

Identifier Type: -

Identifier Source: org_study_id