Clinical trial NCT00140621: A Safety and Efficacy Study of Fabrazyme® Replacement Therapy in Patients With Cardiac Fabry Disease
Official title: A Multicenter Open-label Study of the Safety and Efficacy of α-galactosidase A (R-h α-GAL) Replacement Therapy in Patients With Cardiac Fabry Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fabry Disease
Keywords: cardiac fabry disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2005-09-01
Enrollment: 6
Sex: ALL
Minimum age (years): 20
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multi-center, open label, phase IV study conducted to evaluate the efficacy and safety of agalsidase beta (Fabrazyme \[recombinant form\]) administered by intravenous drip infusion in participants with cardiac Fabry disease.

Participants participated for 4 weeks or less in the baseline period and 156 weeks for the treatment period.


Eligibility criteria: Inclusion Criteria:

* Participants definitively diagnosed with cardiac Fabry disease (who fulfill all of the following criteria)

  * In the case of male participants, documented plasma or leukocyte alpha-galactosidase A (α-GAL) activity was no more than 20 percent (%) of normal value (except for heterozygous female participants)
  * Left ventricular hypertrophy was noted.
  * Accumulation of globotriaosylceramide (GL-3) in the myocardium or a genetic deficiency associated with α-GAL was confirmed
  * Or in the case of heterozygous female participants, when the family (father or son) was diagnosed with Fabry disease. (Father or son was related by birth.)
  * Without symptoms or signs of Fabry, such as acroparesthesia, angiokeratomas, abnormal sweating, pain of distal extremities, chronic abdominal pain/diarrhea and corneal opacities were observed, except for proteinuria sign.
* Participants with interventricular and posterior wall thickness of at least 13 millimeter (mm) on echocardiography within 3 months before signed date to informed consent
* Participants in whom cardiac function was rated as Class I or II according to the New York Heart Association (NYHA) classification when giving informed consent.
* Participants classification: inpatients and outpatients
* Participants who had given written informed consent before the study-related baseline tests.

Exclusion Criteria:

* Participants with severe hypertension (for example, blood pressure more than or equal to 180 millimeter of mercury \[mmHg\] and/or blood pressure more than or equal to 110 mmHg in spite of adequate medication)
* Participants whose serum creatinine level was higher than the upper normal limit within 3 months (12 weeks) prior to giving informed consent.
* Participants who had undergone kidney transplantation or were currently on dialysis.
* Participants with any serious hepatic disorder. Participants who had abnormal hepatic function test values within 3 months (12 weeks) prior to giving informed consent (when either alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] level exceeded the value five times as high as the upper normal limit).
* Permanent pacemaker or defibrillator implanted participants
* Pregnant or lactating women
* Participants who had taken this drug for 6 months (26 weeks) or more before giving informed consent.
* Participants who had participated in a clinical study employing any other investigational product within 3 months prior to giving informed consent.
* Enzyme replacement therapy history, except for agalsidase beta
* Participants who were unwilling to comply with the requirements of the protocol.
* Others judged by the investigator or sub-investigator to be ineligible for the study

Primary outcomes:
measure: Percent Change From Baseline in Interventricular Septum and Left Ventricular Posterior Wall Thickness at Week 156
timeFrame: Baseline to Week 156
measure: Change From Baseline in Interventricular Septum and Left Ventricular Posterior Wall Thickness at Week 156
timeFrame: Baseline to Week 156
measure: Percent Change From Baseline in Left Ventricular Mass (LVM) at Week 156
timeFrame: Baseline to Week 156
measure: Change From Baseline in LVM at Week 156
timeFrame: Baseline to Week 156
Secondary outcomes:
measure: Number of Participants in Overall Cardiac Function Assessment and Clinical Symptoms at Week 156: Change From Baseline in Cardiac Function Test
timeFrame: Baseline to Week 156
measure: Percent Change From Baseline in GL-3 Plasma Levels at Week 156
timeFrame: Baseline to Week 156
measure: Change From Baseline in Short Form (36) Health Survey (SF-36) Scores at Week 156
timeFrame: Baseline to Week 156
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Fujita Health University Hospital
city: Hokkaido
country: Japan
facility: Sapporo Medical University Hospital
city: Kagoshima
country: Japan
facility: Akune Citizen Hospital
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Tokyo
country: Japan
facility: Nihon University Itabashi Hospital
city: Tokyo
country: Japan
facility: Nihon University Nerima Hikarigaoka Hospital
city: Yamanashi
country: Japan
facility: Yamanashi Prefectural Central Hospital
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References: