Fabry DiseaseNCT01745185
Immune Response in Subjects With Fabry Disease Who Are Switching From Agalsidase Alfa to Agalsidase Beta
An observational study of Fabry Disease, run by O & O Alpan LLC at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 years and older
- Conditions the study is for
- Fabry Disease
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to 7 Aug 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: 30 subjects of (7 and above) who meet eligibility criteria.
Who may be able to join
- Confirmed diagnosis of Fabry disease
- Have been treated with ERT using recombinant human agalsidase A.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
Read the 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.
- Conditions
- Fabry Disease
- Keywords
- Fabry Disease, immunity, antibody
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Monitoring antibody formation against agalsidase alfa and beta
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.
Measured: 12 months
Secondary outcomes (1)
Measurement of plasma/urine Gb3 and plasma lyso-Gb3
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2012 (estimated)
- Study startJun 2012
- Primary completion7 Apr 2015
- Study completion7 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- O & O Alpan LLC
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ozlem Goker-Alpan, MD, Principal investigator, O & O Alpan LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01745185
- Sponsor's protocol ID
- 12-CFCT-03
- Status last verified
- Apr 2017
- First submitted
- 5 Dec 2012
- Last updated
- 4 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Benichou B, Goyal S, Sung C, Norfleet AM, O'Brien F. A retrospective analysis of the potential impact of IgG antibodies to agalsidase beta on efficacy during enzyme replacement therapy for Fabry disease. Mol Genet Metab. 2009 Jan;96(1):4-12. doi: 10.1016/j.ymgme.2008.10.004. Epub 2008 Nov 20.
PubMed 19022694
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Response in Subjects With Fabry Disease Who Are Switching From Agalsidase Alfa to Agalsidase Beta
- ClinicalTrials.gov ID
- NCT01745185
- Acronym / sponsor ID
- 12-CFCT-03
- Conditions
- Fabry Disease
- Keywords
- Fabry Disease, immunity, antibody
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- O & O Alpan LLCUniversity, hospital or other
- Study start
- Jun 2012 (actual)
- Primary completion
- 7 Apr 2015 (actual)
- Study completion
- 7 Aug 2016 (actual)
- First posted
- 10 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 7 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- 30 subjects of (7 and above) who meet eligibility criteria.
Key inclusion criteria (2 listed)
- Confirmed diagnosis of Fabry disease
- Have been treated with ERT using recombinant human agalsidase A.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
1 secondary outcome
Measurement of plasma/urine Gb3 and plasma lyso-Gb3
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2017.
- Background: PubMed 19022694Benichou B, Goyal S, Sung C, Norfleet AM, O'Brien F. A retrospective analysis of the potential impact of IgG antibodies to agalsidase beta on efficacy during enzyme replacement therapy for Fabry disease. Mol Genet Metab. 2009 Jan;96(1):4-12. doi: 10.1016/j.ymgme.2008.10.004. Epub 2008 Nov 20.
- O\&O Alpan LLCLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ozlem Goker-Alpan, MD principal investigator
O & O Alpan LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Fabry Disease, run by O & O Alpan LLC at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Monitoring antibody formation against agalsidase alfa and beta (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01745185, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2017.