A Prospective Study to Investigate Safety and Tolerability of Shorter Infusion of Fabrazyme

Study Overview
=================
Brief Summary
-----------------
This Phase 4 study will evaluate the safety and tolerability of Fabrazyme at current approved dose with increases in the infusion rate and reduced infusion volume. This study aims to generate data to provide the guidance on how infusion rate can be safely increased and minimize the burden of the life-long treatment with Fabrazyme.

Detailed Description
-----------------
The total duration will be up to 6 months

Official Title
-----------------
A Study to Investigate Safety and Tolerability of Higher Infusion Rate to shORten the duraTion of FabrazymE Infusion

Conditions
-----------------
Fabry's Disease

Intervention / Treatment
-----------------
* Drug: AGALSIDASE BETA (GZ419828)
* Drug: Acetaminophen
* Drug: Diphenhydramine
* Drug: Dexamethasone
* Drug: Montelukast


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - Participants with confirmed diagnosis of FD who are ≥2 and ≤65 years of age at the time of signing the informed consent form (ICF) or assent, if applicable. Cohort 1: female participants with body weight ≥30 kg who have been treated with Fabrazyme for at least 3 months without IARs during the most recent 3 infusions. Cohort 2: non-classic male participants with body weight ≥30 kg who have been treated with Fabrazyme for at least 3 months without IARs during the most recent 3 infusions. Cohort 3: classic male participants with body weight ≥30 kg who have been treated with Fabrazyme for at least 3 months without IARs during the most recent 3 infusions. Cohort 4: participants with body weight &lt;30 kg who have been treated with Fabrazyme for at least 3 months without IARs during the most recent 3 infusions. Cohort 5: ERT-naïve participants. Women of childbearing potential must use a highly effective method of contraception through the study. Exclusion Criteria: Female participants who are pregnant or breastfeeding. History of significant allergic disease or hypersensitivity to Fabrazyme or other medicinal products. Contraindication to Fabrazyme or any of the premedications or rescue medications (diphenhydramine, acetaminophen, montelukast, dexamethasone). Any other medical condition considered to make the increased infusion rate not tolerable at the Investigator's discretion. The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: agalsidase beta<br>agalsidase beta 1 mg/kg infusion once every other week | Drug: AGALSIDASE BETA (GZ419828)<br>* Pharmaceutical form: Lyophilized powder for reconstitution Route of administration: IV infusion<br>* Other names: Fabrazyme;Drug: Acetaminophen<br>* Tablet or solution; Oral<br>Drug: Diphenhydramine<br>* Tablet or solution; Oral<br>Drug: Dexamethasone<br>* Tablet or solution; Oral<br>Drug: Montelukast<br>* Tablet or chewable tablet or oral granules; Oral<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of infusion duration from pretrial average of recent 3 infusions |  | Baseline to month 4 | 
| Reduction of infusion duration from initial 120 minutes |  | Baseline to month 4 | 
| Shortest infusion duration each participant tolerates |  | Baseline to month 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants achieving the shortest planned duration of infusion time |  | Baseline to month 4 | 
| Percentage of participants achieving the shortest planned duration of infusion time |  | Baseline to month 4 | 
| Number of participants achieving infusion duration shorter than 90 minutes without experiencing any or the second IAR |  | Baseline to month 4 | 
| Percentage of participants achieving infusion duration shorter than 90 minutes without experiencing any or the second IAR |  | Baseline to month 4 | 
| Number of participants achieving infusion duration without experiencing any IAR |  | Baseline to month 4 |