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

NCT00701415 | Completed Phase 3 Results DMC

• 3 other identifiers: AGAL062072007-005668-28EFC12821
• Study Type: interventional
• Target: 31
• Locations: 9 countries
• Sites: 12

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

Keywords

α-GAL, α-Galactosidase-A, r-hαGAL

Outcome Measures

Primary Outcomes (1)

• Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium

  Skin biopsies were taken at Baseline, Week 52, Week 156 and Week 260 or early withdrawal and analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Each biopsy was scored for GL-3 accumulation on a severity score-scale of none, mild, moderate, severe (0-1-2-3). Scores are categorized as normal (score = 0) or abnormal (score = 1, 2 or 3). Data was summarized in terms of number of participants with none/trace, mild, moderate and severe biopsy scores.

  Baseline, Week 52, Week 156 and Week 260

Secondary Outcomes (2)

• Percent Change From Baseline in GL-3 Clearance From Plasma

  Baseline, Week 12, 28, 40, 52, 80, 104, 132, 156, 184, 208, 236 and 260

• Percent Change From Baseline in GL-3 Clearance From Urine

  Baseline, Week 12, 28, 40, 52, 80, 104, 132, 156, 184, 208, 236 and 260

Study Arms (2)

Fabrazyme 0.5 mg/kg

EXPERIMENTAL

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.

Biological: Agalsidase beta

Fabrazyme 1.0 mg/kg

EXPERIMENTAL

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.

Biological: Agalsidase beta

Interventions

Agalsidase beta BIOLOGICAL

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

Also known as: Fabrazyme, Recombinant human α-galactosidase A (r-hαGAL)

Fabrazyme 0.5 mg/kg

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (12)

Unknown Facility

Decatur, Georgia, United States

Location

Unknown Facility

Cincinnati, Ohio, United States

Location

Unknown Facility

Seattle, Washington, United States

Location

Unknown Facility

Buenos Aires, Argentina

Location

Unknown Facility

Passo Fundo, Rio Grande do Sul, Brazil

Location

Unknown Facility

Vancouver, British Columbia, Canada

Location

Unknown Facility

Montreal, QC, Canada

Location

Unknown Facility

Prague, Czechia

Location

Unknown Facility

Amsterdam, Netherlands

Location

Unknown Facility

Bergen, Norway

Location

Unknown Facility

Warsaw, Poland

Location

Unknown Facility

Cambridge, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 25955246 DERIVED

• 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.

  PMID: 23531228 DERIVED

MeSH Terms

Conditions

Fabry Disease

Interventions

agalsidase beta

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2008
• First Posted: June 19, 2008
• Study Start: September 1, 2008
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: June 29, 2016
• Results First Posted: June 29, 2016

Record last verified: 2016-05

Locations

CA (2); BR (1); PL (1); US (3); NL (1); CZ (1); NO (1); GB (1); AR (1)