Clinical trial NCT00701415: A Study of Two Fabrazyme (Agalsidase Beta) Dosing Regimens in Treatment-naïve, Male Pediatric Patients Without Severe Symptoms
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fabry Disease
Keywords: α-GAL, α-Galactosidase-A, r-hαGAL
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2008-06-19
Enrollment: 31
Sex: MALE
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was 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) were effective in treatment-naïve pediatric participants without severe symptoms. Participants were to be treated for 5 years.


Eligibility criteria: Inclusion Criteria:

* The participant and/or participant's parent(s)/legal guardian(s) must provide written informed assent/consent prior to any protocol-related procedures being performed.
* The participant must had a confirmed diagnosis of Fabry disease as documented by leukocyte α-Galactosidase A (αGAL) activity of \<4 nmol/hr/mg leukocyte (preferred assay; resulted from a central laboratory). If the leukocyte αGAL activity assay was difficult to obtain, the participant might be enrolled based on documented plasma αGAL \<1.5 nmol/hr/mL, with the agreement of the Medical Monitor (resulted from a central laboratory).
* The participant must had 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 participant must be male ≥5 and ≤18 years of age.

Exclusion Criteria:

* Participant had 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).
* Participant had 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 might be acceptable, after consultation with the Medical Monitor.
* Participant had documented evidence of stroke or transient ischemic attack (TIA), or if a brain magnetic resonance imaging (MRI) had been performed, bright lesions \>2 mm on T2- or fluid attenuated inversion recovery (FLAIR)- weighted images within the white matter or the basal ganglia.
* Participant had severe and recurrent acroparesthesia, judged by the physician as frequent (more than once a week) pain episodes for at least 3 months that influenced daily activities, irrespective of medication.
* Participant had 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.
* Participant had received prior treatment specific to Fabry Disease.
* Participant had participated in a study employing an investigational drug within 30 days of the start of their participation in this study.
* Participant had any medical condition or extenuating circumstance, which in the opinion of the Study Investigator, could interfere with study compliance.
* Participant had 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.
* Participant was on treatment with angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs).
* Participant had any contra-indication mentioned in the labeling of Fabrazyme and/or iohexol (Omnipaque).
* Participant or parent(s)/legal guardian(s) was unwilling to comply with the requirements of the protocol.

Primary outcomes:
measure: Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium
timeFrame: Baseline, Week 52, Week 156 and Week 260
Secondary outcomes:
measure: Percent Change From Baseline in GL-3 Clearance From Plasma
timeFrame: Baseline, Week 12, 28, 40, 52, 80, 104, 132, 156, 184, 208, 236 and 260
measure: Percent Change From Baseline in GL-3 Clearance From Urine
timeFrame: Baseline, Week 12, 28, 40, 52, 80, 104, 132, 156, 184, 208, 236 and 260
Other outcomes:
Locations:
city: Decatur
country: United States
state: Georgia
city: Cincinnati
country: United States
state: Ohio
city: Seattle
country: United States
state: Washington
city: Buenos Aires
country: Argentina
city: Passo Fundo
country: Brazil
state: RS
city: Vancouver
country: Canada
state: British Columbia
city: Montreal, QC
country: Canada
city: Prague 2
country: Czech Republic
city: Amsterdam
country: Netherlands
city: Bergen
country: Norway
city: Warsaw
country: Poland
city: Cambridge
country: United Kingdom
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Wijburg FA, Benichou B, Bichet DG, Clarke LA, Dostalova G, Fainboim A, Fellgiebel A, Forcelini C, An Haack K, Hopkin RJ, Mauer M, Najafian B, Scott CR, Shankar SP, Thurberg BL, Tondel C, Tylki-Szymanska A, Ramaswami U. Characterization of early disease status in treatment-naive male paediatric patients with Fabry disease enrolled in a randomized clinical trial. PLoS One. 2015 May 8;10(5):e0124987. doi: 10.1371/journal.pone.0124987. eCollection 2015.
citation: Rombach SM, Smid BE, Bouwman MG, Linthorst GE, Dijkgraaf MG, Hollak CE. Long term enzyme replacement therapy for Fabry disease: effectiveness on kidney, heart and brain. Orphanet J Rare Dis. 2013 Mar 25;8:47. doi: 10.1186/1750-1172-8-47.