To assess the glycosphingolipid clearance and clinical benefits of agalsidase beta in male patients with classic Fabry disease switching from agalsidase alfa

• Register: EUCTR
• Last refreshed on: 18 August 2020
• Main ID: EUCTR2019-000064-21-CZ
• Date of registration: 29/08/2019
• Prospective Registration: Yes
• Primary sponsor: Sanofi Aventis Groupe (SAG)
• Public title: To assess the glycosphingolipid clearance and clinical benefits of agalsidase beta in male patients with classic Fabry disease switching from agalsidase alfa
• Scientific title: A randomized, open-label, active comparator, 2-arm, prospective study to assess the glycosphingolipid clearance and clinical effects of switching to agalsidase beta (Fabrazyme) versus continuing on agalsidase alfa (Replagal) in male patients with classic Fabry disease
• Target sample size: 35
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-000064-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Austria, Canada, Czech Republic, Denmark, France, Germany, Italy, Norway, Spain, Turkey, United Kingdom

Contacts

• Name: www.sanofi.cz
• Affiliation: sanofi-aventis, s.r.o.

• Name: www.sanofi.cz
• Affiliation: sanofi-aventis, s.r.o.

Key inclusion & exclusion criteria

Inclusion criteria:
Male participant must be 16 to 45 years of age inclusive, at the time of signing the informed consent.

Participants who are diagnosed with classic Fabry disease based on phenotype, presence or absence of characteristic Fabry disease symptoms including neuropathic pain, clustered angiokeratoma and/or cornea verticillata, leucocyte a-GAL A enzyme activity (3% or less compared to control), and genotype (optional).

Participants who are currently receiving agalsidase alfa for a minimum of 6 months at an average dose of 0.2 mg/kg every other week (ie, every 2 weeks) at baseline.

Participants who are naïve to agalsidase beta.

Participants with estimated glomerular filtration rate (eGFR) =60 mL/min/1.73 m^2 at screening and baseline.

Proteinuria level as measured by 2 separate, morning, clean-catch urine samples taken a few days apart demonstrating an averaged urine protein-creatinine ratio of <0.5 (ie, <500 mg protein per 1 g creatinine) between the 2 samples. For participants on angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), the criterion is to be met both prior and after a temporary interruption of ACEIs/ARBs for 4 weeks.

Participants with plasma lyso-GL3 levels >20 ng/mL on 2 consecutive samples taken at least 4 weeks apart.

Participant’s medical records (including eGFR values) available and accessible during the study period.

Participant and/or participant’s legal representative has given signed informed consent as described in the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. For potential participants age 16 to 18 years, a parent or legal representative is required to sign the ICF, and the potential participant is also required to sign an informed assent form.

Are the trial subjects under 18? yes
Number of subjects for this age range: 4
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 31
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Participants with severe renal impairment (end-stage renal disease, dialysis, or renal transplantation) and/or nephropathies (including diabetic).

Participants with rapid renal decline: Loss of >6mL/min/1.73 m^2 at screening compared to the most recent eGFR value approximately 12 months prior to screening.

Participants with advanced cardiac failure (Stage D).

Participants with bleeding disorder, prior history of unexplained bleeding episodes, or receiving mandatory anticoagulants or antiplatelets for any indication not allowing interruption of therapy for renal biopsy.

Participants with diagnosed diabetes.

Participants with history of anaphylaxis to Enzyme Replacement Therapy (ERT).

Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.

Participants treated for more than 5 years with agalsidase alfa at an average dose of 0.2 mg/kg every other week (ie, every 2 weeks) prior to randomization.

Exposure to migalastat or any investigational study intervention, except agalsidase alfa, for Fabry disease in the last 5 years prior to study participation. Patients who previously participated in any agalsidase alfa clinical study will be eligible if they meet other criteria.

Exposure to any investigational drugs in the last 4 weeks or 5 half­lives, whichever is longer, prior to screening visit or concomitant enrollment in any other clinical study involving an investigational study treatment.

Individuals accommodated in an institution because of regulatory or legal order; prisoners or subjects who are legally institutionalized.

Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.

Participants are dependent on the Sponsor or Investigator or deemed vulnerable for any reason (in conjunction with Section 1.61 of the International Council for Harmonisation Good Clinical Practice [ICH-GCP] Ordinance E6).

Participants who are employees of the clinical study center or other individuals directly involved in the conduct of the study, or immediate family members of such individuals.

Any specific situation during study implementation/course that may raise ethics consideration



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Fabry's disease
MedDRA version: 20.0 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Trade Name: Fabrazyme
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: AGALSIDASE BETA
Current Sponsor code: GZ419828
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: Replagal
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AGALSIDASE ALFA
CAS Number: 104138-64-9
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline, 12 months (week 52)

Primary end point(s): Change in Plasma globotriaosylsphingosine (lyso-GL3) level

Secondary Objective: To assess reduction of kidney podocyte GL3 content after switch to agalsidase beta from agalsidase alfa

To assess reduction of GL3 content in endothelial skin cells after switch to agalsidase beta from agalsidase alfa

To assess change in renal function after switch to agalsidase beta from agalsidase alfa

To assess disease severity and clinical changes after switch to agalsidase beta from agalsidase alfa

To assess improvement in symptoms of Fabry disease after switch to agalsidase beta from agalsidase alfa

Main Objective: To assess reduction of plasma lyso-GL3 level after switch to agalsidase beta from agalsidase alfa

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Timepoint for all secondary end points: Baseline, 12 months (week 52)

Secondary end point(s): 1) Change in GL3 content in podocytes

2) Change in GL3 content in endothelial skin cells

3) Change in measured glomerular filtration rate (mGFR)

4) Change in estimated glomerular filtration rate (eGFR) calculated

5) Change in Mainz Severity Score Index (MSSI) total score

6) Change in Fabry Disease Patient Reported Outcomes (FD-PRO) total symptom score

Secondary ID(s)

LPS15918

2019-000064-21-NO

Source(s) of Monetary Support

Sanofi Aventis Groupe (SAG)