A Study of Two Fabrazyme (Agalsidase Beta) Dosing Regimens in Treatment-naïve, Male Pediatric Patients Without Severe Symptoms

Fabry Disease Clinical Trial

— FIELD  

Official title:

A Randomized, Multicenter, Multinational, Phase 3B, Open-Label, Parallel-Group Study of Fabrazyme (Agalsidase Beta) in Treatment-Naïve Male Pediatric Patients With Fabry Disease Without Severe Symptoms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00701415
• Other study ID #: AGAL06207
• Secondary ID: 2007-005668-28EF
• Status: Completed
• Phase: Phase 3
• First received: June 17, 2008
• Last updated: October 16, 2015
• Start date: September 2008
• Est. completion date: June 2015

Study information

• Verified date: October 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaBrazil: National Health Surveillance AgencyCanada: Ministry of Health & Long Term Care, OntarioNetherlands: Medicines Evaluation Board (MEB)Norway: Norwegian Medicines Agency (NoMA)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products (CBEK)United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether 2 alternative dosing regimens of Fabrazyme (agalsidase beta) (1.0 mg/kg every 4 weeks or 0.5 mg/kg every 2 weeks) are effective in treatment-naïve pediatric patients without severe symptoms. Patients will be treated for 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 5 Years to 18 Years

Eligibility

Inclusion Criteria:

• The patient and/or patient's parent(s)/legal guardian(s) must provide written informed assent/consent prior to any protocol-related procedures being performed.

• The patient must have a confirmed diagnosis of Fabry disease as documented by leukocyte a-Galactosidase A (aGAL) activity of <4 nmol/hr/mg leukocyte (preferred assay; results from a central laboratory). If the leukocyte aGAL activity assay is difficult to obtain, the patient may be enrolled based on documented plasma aGAL <1.5 nmol/hr/mL, with the agreement of the Medical Monitor (results from a central laboratory).

• The patient must have evidence of globotriaosylceramide (GL-3) accumulation as documented by plasma GL-3 (>7.0 µg/mL) or urinary GL-3 (>0.3 mg GL-3/mmol creatinine) levels (results from a central laboratory).

• The patient must be male =5 and =18 years of age.

Exclusion Criteria:

• Patient has albuminuria (first morning void urinary albumin/creatinine ratio >30 mg/g on at least 2 out of 3 consecutive samples, each at least 1 week apart).

• Patient has a Glomerular Filtration Rate (GFR) by iohexol <90 L/min/1.73m^2. In case of properly documented low protein intake, values as low as 80 mL/min/1.73 m^2 may be acceptable, after consultation with the Medical Monitor.

• Patient has documented evidence of stroke or transient ischemic attack (TIA), or if a brain magnetic resonance imaging (MRI) has been performed, bright lesions >2 mm on T2- or fluid attenuated inversion recovery (FLAIR)- weighted images within the white matter or the basal ganglia.

• Patient has severe and recurrent acroparesthesia, judged by the physician as frequent (more than once a week) pain episodes for at least 3 months that influence daily activities, irrespective of medication.

• Patient has an end-diastolic left ventricular posterior wall thickness (LVPWTd) and/or an end-diastolic interventricular septum thickness (IVSTd)=2 standard deviations (SD) compared to normal (based on body surface area [BSA] normal ranges from Kampmann, et al 2000) as read at the study site.

• Patient has received prior treatment specific to Fabry Disease.

• Patient has participated in a study employing an investigational drug within 30 days of the start of their participation in this study.

• Patient has any medical condition or extenuating circumstance, which in the opinion of the Study Investigator, could interfere with study compliance.

• Patient has any medical condition or extenuating circumstance, for example diabetes mellitus, which in the opinion of the Study Investigator, could interfere with the interpretation of study results.

• Patient is on treatment with angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs).

• Patient has any contra-indication mentioned in the labeling of Fabrazyme and/or iohexol (Omnipaque).

• Patient or parent(s)/legal guardian(s) is unwilling to comply with the requirements of the protocol.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fabry Disease

Intervention

Biological:
• agalsidase beta
1.0 mg/kg/4 weeks
• agalsidase beta
0.5 mg/kg/2 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Czech Republic,  Netherlands,  Norway,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	globotriaosylceramide (GL-3) inclusion in skin vascular endothelium		Up to Week 260/Year 5	No
Secondary	GL-3 clearance in Plasma		Up to month 60	No
Secondary	GL-3 clearance in Urine		Up to month 60	No