Clinical trial NCT01363492: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fabry Disease
Keywords: agalsidase alfa
Replagal
Enzyme Replacement Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-06-01
Enrollment: 15
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

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

1. 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.
2. The patient is 7 to \<18 years of age
3. The patient is ERT-naïve
4. 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
5. 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.

1. 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
2. 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.
3. Otherwise unsuitable for the study, in the opinion of the Investigator.

Primary outcomes:
measure: Number of Serious Adverse Event (SAE)
timeFrame: Baseline to week 55
measure: Number of Treatment Emergent Adverse Event (TEAE)
timeFrame: Baseline to week 55
measure: Development of IgG Anti-Agalsidase Alfa Antibody
timeFrame: Baseline to Week 55
measure: Change From Baseline in Heart Rate Variability Parameter SDNN
timeFrame: Baseline to week 55
measure: Change From Baseline in Heart Rate Variability Parameter rMSSD
timeFrame: Baseline to week 55
measure: Change From Baseline in Heart Rate Variability Parameter pNN50
timeFrame: Baseline to week 55
Secondary outcomes:
measure: Change From Baseline in LVMI
timeFrame: Baseline to week 55
measure: Change From Baseline in MFS
timeFrame: Baseline to week 55
measure: Change From Baseline in Plasma Gb3
timeFrame: Baseline to week 55
measure: Change From Baseline in Urine Gb3
timeFrame: Baseline to week 55
Other outcomes:
Locations:
city: Decatur
country: United States
facility: Emory Division of Medical Genetics
state: Georgia
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Fairfax
country: United States
facility: O & O Alpan LLC
state: Virginia
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
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.