A Study Evaluating Glycosphingolipid Clearance in Patients Treated With Agalsidase Alfa Who Switch to Agalsidase Beta

Evaluation of Glycosphingolipid Clearance in Patients Treated With Agalsidase Alfa Who Switch to Agalsidase Beta (The INFORM Study)

This is an exploratory study to evaluate changes in glycosphingolipid levels and other (exploratory) Fabry disease parameters in male Fabry disease participants who were previously treated with agalsidase alfa (Replagal®) 0.2 milligram per kilogram (mg/kg) every two weeks (q2w) and who are being switched to agalsidase beta (Fabrazyme®) 1.0 mg/kg q2w.

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Biological: Agalsidase beta

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Coral Springs, Florida, United States
  • Georgia
    • Decatur, Georgia, United States
  • Maryland
    • Baltimore, Maryland, United States
  • Michigan
    • Grand Rapids, Michigan, United States
  • Pennsylvania
    • Hellertown, Pennsylvania, United States
  • Virginia
    • Fairfax, Virginia, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• The participant and/or his parent/legal guardian is willing and able to provide signed informed consent, and the participant, if less than (<) 18 years of age, is willing to provide assent if deemed able to do so
• Participant is male and has been treated with agalsidase alfa at 0.2 mg/kg q2w for the 12 months prior to switching to agalsidase beta
• The participant has a confirmed diagnosis of Fabry disease by alfa-galactosidase A (alfa-GAL) activity and/or genotyping per local standards
• The participant when switched to agalsidase beta receives the labeled dose, that is, 0.9 to 1.1 mg/kg (1 mg/kg) q2w, and must be willing to maintain the labeled dose for the duration of the study

Exclusion Criteria:

• The participant is on dialysis or is post renal transplantation
• The participant is in end-stage cardiac failure
• The participant and/or his parent or legal guardian, in the opinion of the investigator, is unable to adhere to the requirements of the study
• The participant has been switched from agalsidase alfa to agalsidase beta and does not have historical blood and urine samples

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Agalsidase beta	Biological: Agalsidase beta; Commercially available agalsidase beta 1.0 mg/kg administered as an intravenous infusion q2w up to Month 6.; Other Names: Fabrazyme®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Plasma Deacylated Globotriaosylceramide (Lyso-GL-3) at Month 2, 4 and 6	Percent change from baseline = ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. For levels reported as below quantitative limit (BQL), the lower limit of quantitation (LLOQ) value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for plasma lyso-GL-3 was 5.0 nanogram per milliliter (ng/mL). This study is exploratory because little is known about the dose-response of these biomarkers to enzyme replacement therapy (ERT) or about the clinical significance of the biomarkers.	Baseline, Month 2, 4, 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Plasma Globotriaosylceramide (GL-3) at Month 2, 4 and 6	Percent change from baseline = ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. For levels reported as BQL, the LLOQ value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for plasma GL-3 was 2.0 microgram per milliliter (mcg/mL). This study is exploratory because little is known about the dose-response of these biomarkers to ERT or about the clinical significance of the biomarkers.	Baseline, Month 2, 4, 6
Percent Change From Baseline in Urine GL-3 at Month 2, 4, and 6	Percent change from baseline = ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. For levels reported as BQL, the LLOQ value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for urine GL-3 was 0.2 mcg/mL. The absolute values were calculated in microgram per millimole (mcg/mmol) of creatinine by dividing GL-3 (mcg/mL) by creatinine (mg/mL) and multiplying by 113.13 (mg/mmol), the molecular weight of creatinine. For levels reported BQL, the absolute values were calculated in microgram per millimole (mcg/mmol) of creatinine by dividing 0.1 (mcg/mL) by creatinine (mg/mL) and multiplying by 133.13 (mg/mmol). This study is exploratory because little is known about the dose-response of these biomarkers to ERT or about the clinical significance of the biomarkers.	Baseline, Month 2, 4, 6
Percent Change From Baseline in Gastrointestinal (GI) Symptoms (Abdominal Pain, Abdominal Distention, and Bowel Irregularities) at Month 2, 4, and 6	Gastrointestinal symptoms (abdominal pain, abdominal distention, and irregular bowel movements) were to be assessed by a modified version of the Irritable Bowel Syndrome (IBS) Severity Scoring System. The modified IBS Severity Scoring System is a 7-item questionnaire. The severity score calculated by summing the scores of 5 of the 7 questions. Each of the 5 questions were scored on a scale of 0 to 100, leading to a total possible score range of 0 to 500, where higher scores indicate more severe gastrointestinal symptoms. The data for this outcome measure was exploratory and to be collected in individual participant listing only.	Baseline, Month 2, 4, 6

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: July 24, 2012
• First Submitted That Met QC Criteria: July 25, 2012
• First Posted (Estimate): July 26, 2012

Study Record Updates

• Last Update Posted (Estimate): July 10, 2014
• Last Update Submitted That Met QC Criteria: June 9, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Fabry; GL-3; Fabrazyme; alpha-galactosidase A; a-GAL
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: AGAL19412

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No