A Study of Two Fabrazyme (Agalsidase Beta) Dosing Regimens in Treatment-naïve, Male Pediatric Patients Without Severe Symptoms

NCT ID: NCT00701415

Last Updated: 2016-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2015-06-30

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.

Conditions

Fabry Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fabrazyme 0.5 mg/kg

Fabrazyme 0.5 mg/kg was administered every 2 weeks (up to 131 infusion) up to 260 weeks, the total infusion time was not less than 45 minutes. In case of significant progression of Fabry disease, the dose was increased to 1.0 mg/kg every 2 weeks.

Group Type: EXPERIMENTAL

Agalsidase beta

Intervention Type: BIOLOGICAL

Powder for concentrate for solution for infusion 1.0 mg/kg/4 weeks

Fabrazyme 1.0 mg/kg

Fabrazyme 1.0 mg/kg was administered every 4 weeks (up to 66 infusion) up to 260 weeks, the total infusion time was not less than 90 minutes. In case of significant progression of Fabry disease, the dose was increased to 1.0 mg/kg every 2 weeks.

Group Type: EXPERIMENTAL

Agalsidase beta

Intervention Type: BIOLOGICAL

Powder for concentrate for solution for infusion 0.5 mg/kg/2 weeks

Interventions

Agalsidase beta

Powder for concentrate for solution for infusion 1.0 mg/kg/4 weeks

Intervention Type: BIOLOGICAL

Agalsidase beta

Powder for concentrate for solution for infusion 0.5 mg/kg/2 weeks

Intervention Type: BIOLOGICAL

Other Intervention Names

Fabrazyme; Recombinant human α-galactosidase A (r-hαGAL); Fabrazyme; Recombinant human α-galactosidase A (r-hαGAL)

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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Genzyme, a Sanofi Company

Locations

Decatur, Georgia, United States

Cincinnati, Ohio, United States

Seattle, Washington, United States

Buenos Aires, , Argentina

Passo Fundo, Rio Grande do Sul, Brazil

Vancouver, British Columbia, Canada

Montreal, QC, , Canada

Prague, , Czechia

Amsterdam, , Netherlands

Bergen, , Norway

Warsaw, , Poland

Cambridge, , United Kingdom

Countries

United States; Argentina; Brazil; Canada; Czechia; Netherlands; Norway; Poland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 25955246 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23531228 (View on PubMed)

Other Identifiers

2007-005668-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC12821

Identifier Type: OTHER

Identifier Source: secondary_id

AGAL06207

Identifier Type: -

Identifier Source: org_study_id