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

NCT02800070 | Completed Phase 1 DMC

• 1 other identifier: OZM-074
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

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

Keywords

autologous stem cell transplant; gene therapy; Fabry disease; lentivirus; haematopoietic stem cell transplant

Outcome Measures

Primary Outcomes (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.

  5 years

Secondary Outcomes (11)

• Alpha-gal A enzyme activity levels

  5 years

• Gb3 levels

  5 years

• lyso-Gb3 levels

  5 years

• lyso-Gb3 analogue (-28)

  5 years

• lyso-Gb3 analogue (-2)

  5 years

Study Arms (1)

Treatment Arm

EXPERIMENTAL

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

Biological: Lentivirus Alpha-gal A transduced stem cells

Interventions

Lentivirus Alpha-gal A transduced stem cells BIOLOGICAL

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Ozmosis Research Inc.: collaborator

Study Sites (3)

Alberta Children's Hospital, University of Calgary

Calgary, Alberta, Canada

Location

QE II Health Sciences Centre

Halifax, Nova Scotia, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Location

Related Publications (1)

• 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.

  PMID: 33633114 DERIVED

MeSH Terms

Conditions

Fabry Disease

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2016
• First Posted: June 15, 2016
• Study Start: July 1, 2016
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: April 17, 2024

Record last verified: 2024-04

Locations

CA (3)