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Trial record 1 of 30 for:    sanofi | fabry
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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 (BCLEAR1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04143958
Recruitment Status : Withdrawn (The Sponsor terminated the study due to recruitment infeasibility without having enrolled any patient.)
First Posted : October 30, 2019
Last Update Posted : August 12, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

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

Secondary Objectives:

  • 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

Condition or disease Intervention/treatment Phase
Fabry's Disease Drug: agalsidase beta (GZ419828) Drug: agalsidase alfa Phase 4

Detailed Description:
The study will have a screening period of up to 9 weeks. Eligible participants will be randomized to switch to agalsidase beta or to continue agalsidase alfa in a 1:1 ratio for a period of 12 months (52 weeks).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Estimated Study Start Date : September 2020
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : November 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: agalsidase beta
Commercially available agalsidase beta treatment at approved dose and regimen;administered once every 2 weeks as an IV infusion
Drug: agalsidase beta (GZ419828)
Pharmaceutical form:Powder for concentrate for solution for infusion Route of administration: Intravenous (IV) infusion,

Active Comparator: agalsidase alfa
Commercially available agalsidase alfa treatment at approved dose and regimen; administered once every 2 weeks as an IV infusion
Drug: agalsidase alfa
Pharmaceutical form:concentrate for solution for infusion Route of administration: Intravenous (IV) infusion




Primary Outcome Measures :
  1. Change in Plasma globotriaosylsphingosine (lyso-GL3) level [ Time Frame: Baseline, 12 months (week 52) ]
    Change from baseline to 12 months (week 52) for plasma lyso-GL3 level


Secondary Outcome Measures :
  1. Change in GL3 content in podocytes [ Time Frame: Baseline, 12 months (week 52) ]
    Change from baseline to 12 months (week 52) for GL3 content in podocytes

  2. Change in GL3 content in endothelial skin cells [ Time Frame: Baseline, 12 months (week 52) ]
    Change from baseline to 12 months (Week 52) for GL3 content in endothelial skin cells

  3. Change in measured glomerular filtration rate (mGFR) [ Time Frame: Baseline, 12 months (week 52) ]
    Change from baseline to 12 months (Week 52) for measured glomerular filtration rate (mGFR) (measured by iohexol clearance)

  4. Change in estimated glomerular filtration rate (eGFR) calculated [ Time Frame: Baseline, 12 months (week 52) ]
    Change from baseline to 12 months (Week 52) for estimated glomerular filtration rate (eGFR) calculated using age appropriate formula [Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)/ Bedside-Schwartz]

  5. Change in Mainz Severity Score Index (MSSI) total score [ Time Frame: Baseline, 12 months (week 52) ]
    Change from baseline to 12 months (Week 52) for Mainz Severity Score Index (MSSI), based on MSSI total score

  6. Change in Fabry Disease Patient Reported Outcomes (FD-PRO) total symptom score [ Time Frame: Baseline, 12 months (week 52) ]
    Change from baseline to 12 months (Week 52) in Fabry Disease Patient Reported Outcomes (FD-PRO) score, based on FD-PRO total symptom score



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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 α-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.

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 half-lives, 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

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04143958


Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04143958    
Other Study ID Numbers: LPS15918
2019-000064-21 ( EudraCT Number )
U1111-1223-5105 ( Other Identifier: UTN )
First Posted: October 30, 2019    Key Record Dates
Last Update Posted: August 12, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Fabry Disease
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
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders