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

Fabry Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01650779
• Other study ID #: AGAL19412
• Status: Completed
• Phase: Phase 4
• First received: July 24, 2012
• Last updated: June 9, 2014
• Start date: April 2012
• Est. completion date: March 2013

Study information

• Verified date: June 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fabry Disease

Intervention

Biological:
• Agalsidase beta
Commercially available agalsidase beta 1.0 mg/kg administered as an intravenous infusion q2w up to Month 6.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No