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Safety Study of Replagal® Therapy in Children With Fabry Disease

Primary Purpose

Fabry Disease

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Replagal (agalsidase alfa)

About this trial

This is an interventional treatment trial for Fabry Disease focused on measuring agalsidase alfa, Replagal, Enzyme Replacement Therapy

Eligibility Criteria

7 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must meet all of the following criteria to be enrolled in this study.

All patients must be diagnosed with Fabry disease by the following criteria:
- Male Patients: The patient is a hemizygous male with Fabry disease as confirmed by a deficiency of alfa-galactosidase A activity measured in serum, leukocytes, or fibroblasts or has a confirmed mutation of the alfa-galactosidase-A gene.
- Female Patients: The patient is a heterozygous female with Fabry disease as confirmed by a mutation of the alfa-galactosidase A gene.
Note: If the diagnosis of Fabry disease is previously documented in the patient's medical record, screening tests do not need to be repeated.
The patient is 7 to <18 years of age
The patient is ERT-naïve
Adequate general health (as determined by the Investigators) to undergo the specified phlebotomy regimen and protocol-related procedures and no safety or medical contraindications for participation
The minor child must assent to participate in the protocol and the parent(s) or legally authorized representative(s) must have voluntarily signed an Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved informed consent form after all relevant aspects of the study have been explained and discussed with the child and the child's parent(s) or legally authorized representative(s)

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from the study.

Patient and/or the patient's parent(s) or legally authorized representative(s) are unable to understand the nature, scope, and possible consequences of the study
Patient is unable to comply with the protocol, eg, uncooperative with protocol schedule, refusal to agree to all of the study procedures, inability to return for evaluations, or is otherwise unlikely to complete the study, as determined by the Investigator or the medical monitor.
Otherwise unsuitable for the study, in the opinion of the Investigator.

Sites / Locations

Emory Division of Medical Genetics
Duke University Medical Center
Baylor University Medical Center
University of Utah Hospital
O & O Alpan LLC

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Replagal 0.2 mg/kg every other week (EOW)

Arm Description

Outcomes

Primary Outcome Measures

Number of Serious Adverse Event (SAE)

Number of Treatment Emergent Adverse Event (TEAE)

Development of IgG Anti-Agalsidase Alfa Antibody

Reflects development of Anti-Agalsidase antibodies post baseline

Change From Baseline in Heart Rate Variability Parameter SDNN

Change From Baseline in Heart Rate Variability Parameter rMSSD

Change From Baseline in Heart Rate Variability Parameter pNN50

Secondary Outcome Measures

Change From Baseline in LVMI

Change From Baseline in MFS

Change From Baseline in Plasma Gb3

Change From Baseline in Urine Gb3

Full Information

NCT ID

NCT01363492

First Posted

March 31, 2011

Last Updated

May 24, 2021

Sponsor

Shire

1. Study Identification

Unique Protocol Identification Number

NCT01363492

Brief Title

Safety Study of Replagal® Therapy in Children With Fabry Disease

Official Title

An Open-Label Clinical Trial of Replagal® Enzyme Replacement Therapy in Children With Fabry Disease Who Are Naive to Enzyme Replacement Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Completed

Study Start Date

May 12, 2011 (Actual)

Primary Completion Date

April 17, 2013 (Actual)

Study Completion Date

April 17, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shire

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to assess the safety of Replagal in children with Fabry disease who who have not previously been treated with enzyme replacement therapy (ERT).

Detailed Description

In 2008, a change in the agalsidase alfa drug substance manufacturing process was made. There are no changes to the drug product formulation, manufacturing site, manufacturing process, or container closure. An agalsidase alfa bioreactor manufacturing process (agalAF1) utilizing animal component-free media replaced the previous roller bottle (RB) process. This study will evaluate the safety of Replagal AF, manufactured using the new bioreactor process at a dose of 0.2 mg/kg infused IV over 40 minutes, every other week (EOW) in children with Fabry disease who are 7 years to less than 18 years of age and who are naive to ERT.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Fabry Disease

Keywords

agalsidase alfa, Replagal, Enzyme Replacement Therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Replagal 0.2 mg/kg every other week (EOW)

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

Replagal (agalsidase alfa)

Other Intervention Name(s)

agalsidase alfa

Intervention Description

0.2 mg/kg administered over 40 minutes every other week (EOW)

Primary Outcome Measure Information:

Title

Number of Serious Adverse Event (SAE)

Time Frame

Baseline to week 55

Title

Number of Treatment Emergent Adverse Event (TEAE)

Time Frame

Baseline to week 55

Title

Development of IgG Anti-Agalsidase Alfa Antibody

Description

Reflects development of Anti-Agalsidase antibodies post baseline

Time Frame

Baseline to Week 55

Title

Change From Baseline in Heart Rate Variability Parameter SDNN

Time Frame

Baseline to week 55

Title

Change From Baseline in Heart Rate Variability Parameter rMSSD

Time Frame

Baseline to week 55

Title

Change From Baseline in Heart Rate Variability Parameter pNN50

Time Frame

Baseline to week 55

Secondary Outcome Measure Information:

Title

Change From Baseline in LVMI

Time Frame

Baseline to week 55

Title

Change From Baseline in MFS

Time Frame

Baseline to week 55

Title

Change From Baseline in Plasma Gb3

Time Frame

Baseline to week 55

Title

Change From Baseline in Urine Gb3

Time Frame

Baseline to week 55

10. Eligibility

Sex

All

Minimum Age & Unit of Time

7 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must meet all of the following criteria to be enrolled in this study. All patients must be diagnosed with Fabry disease by the following criteria: Male Patients: The patient is a hemizygous male with Fabry disease as confirmed by a deficiency of alfa-galactosidase A activity measured in serum, leukocytes, or fibroblasts or has a confirmed mutation of the alfa-galactosidase-A gene. Female Patients: The patient is a heterozygous female with Fabry disease as confirmed by a mutation of the alfa-galactosidase A gene. Note: If the diagnosis of Fabry disease is previously documented in the patient's medical record, screening tests do not need to be repeated. The patient is 7 to <18 years of age The patient is ERT-naïve Adequate general health (as determined by the Investigators) to undergo the specified phlebotomy regimen and protocol-related procedures and no safety or medical contraindications for participation The minor child must assent to participate in the protocol and the parent(s) or legally authorized representative(s) must have voluntarily signed an Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved informed consent form after all relevant aspects of the study have been explained and discussed with the child and the child's parent(s) or legally authorized representative(s) Exclusion Criteria: Patients who meet any of the following criteria will be excluded from the study. Patient and/or the patient's parent(s) or legally authorized representative(s) are unable to understand the nature, scope, and possible consequences of the study Patient is unable to comply with the protocol, eg, uncooperative with protocol schedule, refusal to agree to all of the study procedures, inability to return for evaluations, or is otherwise unlikely to complete the study, as determined by the Investigator or the medical monitor. Otherwise unsuitable for the study, in the opinion of the Investigator.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Study Director

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

Facility Name

Emory Division of Medical Genetics

City

Decatur

State/Province

Georgia

ZIP/Postal Code

30033

Country

United States

Facility Name

Duke University Medical Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

Baylor University Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75246

Country

United States

Facility Name

University of Utah Hospital

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84132

Country

United States

Facility Name

O & O Alpan LLC

City

Fairfax

State/Province

Virginia

ZIP/Postal Code

22152

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

27307708

Citation

Goker-Alpan O, Longo N, McDonald M, Shankar SP, Schiffmann R, Chang P, Shen Y, Pano A. An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naive to enzyme replacement therapy. Drug Des Devel Ther. 2016 May 25;10:1771-81. doi: 10.2147/DDDT.S102761. eCollection 2016.

Results Reference

derived

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Safety Study of Replagal® Therapy in Children With Fabry Disease

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