Immune Response in Subjects With Fabry Disease Who Are Switching From Agalsidase Alfa to Agalsidase Beta

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by O & O Alpan LLC
Sponsor:
Information provided by (Responsible Party):
O & O Alpan LLC
ClinicalTrials.gov Identifier:
NCT01745185
First received: December 5, 2012
Last updated: September 16, 2013
Last verified: September 2013
  Purpose

This study is a prospective active comparator study to assess the immune response elicited by human recombinant agalsidase therapy in subjects who are switching from agalsidase alfa to agalsidase beta with Fabry disease. Fabry disease is an X-linked lysosomal storage disorder, due to deficient alpha-galactosidase A activity. The progressive accumulation of globotriaosylceramide (GL-3) in the lysosomes of the vascular endothelial cells of multiple organ systems like the kidneys, heart, skin, and brain, leads to a microvascular disease. In Fabry disease, nephropathy dominates and renal function impairment occurs as a result of accumulation of GL-3 in renal cells


Condition
Fabry Disease

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Immune Response in Subjects With Fabry Disease Who Are Switching From Agalsidase Alfa to Agalsidase Beta

Resource links provided by NLM:


Further study details as provided by O & O Alpan LLC:

Primary Outcome Measures:
  • Monitoring antibody formation against agalsidase alfa and beta [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Blood samples will be collected prior to infusion (screening & month 12). At baseline, antibodies against agalsidase alfa and beta measured, and at 12 months, antibodies against agalsidase beta will be measured by ELISA technique and will be isotyped immunoglobulins (IgG, IgA, IgM, or IgE). Positive samples will subsequently tested for enzyme neutralizing activity using an in vitro assay. Antibody measurements will be done by Shire Human Genetics Therapies, INC.


Secondary Outcome Measures:
  • Measurement of plasma/urine Gb3 and plasma lyso-Gb3 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Plasma samples collected after at least 8 hours of fasting prior to the blood draw. Plasma and urine samples (Gb3 only) analyzed using mass spectrometry. Gb3 measurements will be performed by Shire HGT.


Biospecimen Retention:   Samples With DNA

Blood, Urine


Estimated Enrollment: 30
Study Start Date: June 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Fabry disease switch group
Subjects will include individuals with Fabry disease who are switching from agalsidase alfa to agalsidase beta
Control Group
Controls will include individuals with Fabry disease who have only received agalsidase beta as treatment in their lifetime.

Detailed Description:

Clinically, the development of an immune response is anticipated in a number of patients treated with any recombinant human proteins and suggested to be more common especially when the native protein is deficient or absent as many male patients with Fabry disease.

The immune response that results in the development of antibodies against the infused proteins may affect the clinical outcome of enzyme replacement therapy by the development of hypersensitivity, anaphylactoid, or febrile reactions, or may lead to the development of cytokine release and a generalized inflammatory response or immune complex formation. Furthermore, the mounted immune response may lead to inactivation or degradation of the recombinant enzyme or may change the pharmacokinetic and pharmacodynamic properties of the therapeutic protein.

The different rates of antibody formation with agalsidase alfa and agalsidases beta are often attributed to differences in techniques used to measure antibody formation. However, other factors such as host, structural similarity of the infused protein and tertiary structural difference such as glycosylation may lead to differences in the immune response. Among the factors that may affect host response are also the dose and the infusion frequency. Although agalsidase alfa and beta are derived from the same complementary DNA sequence there are minor differences in glycosylation patterns, and different dosing is used, 0.2 mg per kg every other week for agalsidase alfa, 1.0 mg per kg for agalsidase beta.

The investigator hypothesize that although the observation that the antibodies exhibit in vitro neutralizing capacity may suggest the presence of a single immunogenic epitope for both human recombinant alpha-galactosidases, the immunogenicity may not be similar for both agalsidase alfa and beta, and thus the differences in immune response will be determined by the host factors and the escalating dose of infused protein.

  Eligibility

Ages Eligible for Study:   7 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

30 subjects of (7 and above) who meet eligibility criteria.

Criteria

Inclusion Criteria:

  • Confirmed diagnosis of Fabry disease
  • Have been treated with ERT using recombinant human agalsidase A.

Exclusion Criteria:

  • If the diagnosis of Fabry disease is not confirmed
  • If the subject or guardian is not able to provide consent
  • Any chronic immunosuppressive state or therapy such as patients on dialysis or post-transplantation immunosuppressive therapy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01745185

Contacts
Contact: Ozlem Goker-Alpan, MD 571-308-1904 ogokeralpan@oandoalpan.com

Locations
United States, Virginia
O&O Alpan Recruiting
Fairfax, Virginia, United States, 22030
Contact: Tabitha Taber    571-308-1906    ttaber@oandoalpan.com   
Contact: Amanda Hebert, MS    571-308-1907    ahebert@oandoalpan.com   
Sponsors and Collaborators
O & O Alpan LLC
Investigators
Principal Investigator: Ozlem Goker-Alpan, MD O & O Alpan LLC
  More Information

Additional Information:
Publications:
Responsible Party: O & O Alpan LLC
ClinicalTrials.gov Identifier: NCT01745185     History of Changes
Other Study ID Numbers: 12-CFCT-03
Study First Received: December 5, 2012
Last Updated: September 16, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by O & O Alpan LLC:
Fabry Disease
immunity
antibody

Additional relevant MeSH terms:
Fabry Disease
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
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on September 16, 2014