Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT01650779
First received: July 24, 2012
Last updated: June 9, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Fabry Disease
Biological: Agalsidase beta
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Glycosphingolipid Clearance in Patients Treated With Agalsidase Alfa Who Switch to Agalsidase Beta (The INFORM Study)

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percent Change From Baseline in Plasma Deacylated Globotriaosylceramide (Lyso-GL-3) at Month 2, 4 and 6 [ Time Frame: Baseline, Month 2, 4, 6 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percent Change From Baseline in Plasma Globotriaosylceramide (GL-3) at Month 2, 4 and 6 [ Time Frame: Baseline, Month 2, 4, 6 ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Urine GL-3 at Month 2, 4, and 6 [ Time Frame: Baseline, Month 2, 4, 6 ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Gastrointestinal (GI) Symptoms (Abdominal Pain, Abdominal Distention, and Bowel Irregularities) at Month 2, 4, and 6 [ Time Frame: Baseline, Month 2, 4, 6 ] [ Designated as safety issue: No ]
    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.


Enrollment: 15
Study Start Date: April 2012
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Fabrazyme®

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01650779

Locations
United States, Florida
Coral Springs, Florida, United States
United States, Georgia
Decatur, Georgia, United States
United States, Maryland
Baltimore, Maryland, United States
United States, Michigan
Grand Rapids, Michigan, United States
United States, Pennsylvania
Hellertown, Pennsylvania, United States
United States, Virginia
Fairfax, Virginia, United States
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01650779     History of Changes
Other Study ID Numbers: AGAL19412
Study First Received: July 24, 2012
Results First Received: June 9, 2014
Last Updated: June 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
alpha-galactosidase A
a-GAL
Fabry
GL-3
Fabrazyme

Additional relevant MeSH terms:
Fabry Disease
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Cardiovascular Diseases
Central Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lipidoses
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Sphingolipidoses
Vascular Diseases

ClinicalTrials.gov processed this record on November 25, 2014