We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 31 for:    O&O ALPAN
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01745185
Recruitment Status : Completed
First Posted : December 10, 2012
Last Update Posted : April 4, 2017
Sponsor:
Information provided by (Responsible Party):
O & O Alpan LLC

Study Description
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
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 or disease
Fabry Disease

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.

Study Design
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Immune Response in Subjects With Fabry Disease Who Are Switching From Agalsidase Alfa to Agalsidase Beta
Actual Study Start Date : June 2012
Actual Primary Completion Date : April 7, 2015
Actual Study Completion Date : August 7, 2016

Resource links provided by the National Library of Medicine


Groups and Cohorts
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort
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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Monitoring antibody formation against agalsidase alfa and beta [ Time Frame: 12 months ]
    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 :
  1. Measurement of plasma/urine Gb3 and plasma lyso-Gb3 [ Time Frame: 12 months ]
    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

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   7 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01745185


Locations
Layout table for location information
United States, Virginia
O&O Alpan
Fairfax, Virginia, United States, 22030
Sponsors and Collaborators
O & O Alpan LLC
Investigators
Layout table for investigator information
Principal Investigator: Ozlem Goker-Alpan, MD O & O Alpan LLC
More Information
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Publications:

Layout table for additonal information
Responsible Party: O & O Alpan LLC
ClinicalTrials.gov Identifier: NCT01745185    
Other Study ID Numbers: 12-CFCT-03
First Posted: December 10, 2012    Key Record Dates
Last Update Posted: April 4, 2017
Last Verified: April 2017
Keywords provided by O & O Alpan LLC:
Fabry Disease
immunity
antibody
Additional relevant MeSH terms:
Layout table for 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