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WithdrawnNCT04143958BCLEAR1Updated Apr 7, 2023

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

A Phase 4 interventional study of agalsidase beta (GZ419828) and agalsidase alfa in Fabry Disease, sponsored by Sanofi. Withdrawn. Open to male participants aged 16 Years to 45 Years. Per ClinicalTrials.gov, last updated 2023-04-07.

Sponsored by Sanofi · Phase 4, Interventional, and Treatment

Why this study was withdrawn
The Sponsor terminated the study due to recruitment infeasibility without having enrolled any patient.
Phase
Phase 4
Study type
Interventional
Enrollment
0
Allocation
Randomized
Ages
16 Years to 45 Years
Sex
Male
01

Study 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
Read the 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).

02

Conditions studied

  • Fabry Disease

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03

In context

Fabry Disease

242 studies on the registry are indexed under Fabry Disease; 54 are open to participants now.

Browse Fabry Disease studies →

Lead sponsor

Sanofi is the lead sponsor of 1,508 studies on the registry; 90 are open to participants now.

Of its 198 completed or terminated interventional studies of FDA-regulated products, 118 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
16 Years to 45 Years
Sexes eligible
Male
Accepts healthy volunteers
No

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

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.

05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
0 participants (actual)

Study arms

  • 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)

  • 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

Interventions

  • Drugagalsidase beta (GZ419828)

    Pharmaceutical form:Powder for concentrate for solution for infusion Route of administration: Intravenous (IV) infusion,

  • Drugagalsidase alfa

    Pharmaceutical form:concentrate for solution for infusion Route of administration: Intravenous (IV) infusion

06

What researchers measure

Primary outcomes

  1. Change in Plasma globotriaosylsphingosine (lyso-GL3) level

    Change from baseline to 12 months (week 52) for plasma lyso-GL3 level

    Time frame: Baseline, 12 months (week 52)

Secondary outcomes

  1. Change in GL3 content in podocytes

    Change from baseline to 12 months (week 52) for GL3 content in podocytes

    Time frame: Baseline, 12 months (week 52)

  2. Change in GL3 content in endothelial skin cells

    Change from baseline to 12 months (Week 52) for GL3 content in endothelial skin cells

    Time frame: Baseline, 12 months (week 52)

  3. Change in measured glomerular filtration rate (mGFR)

    Change from baseline to 12 months (Week 52) for measured glomerular filtration rate (mGFR) (measured by iohexol clearance)

    Time frame: Baseline, 12 months (week 52)

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

    Change from baseline to 12 months (Week 52) for estimated glomerular filtration rate (eGFR) calculated using age appropriate formula \[Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)/ Bedside-Schwartz\]

    Time frame: Baseline, 12 months (week 52)

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

    Change from baseline to 12 months (Week 52) for Mainz Severity Score Index (MSSI), based on MSSI total score

    Time frame: Baseline, 12 months (week 52)

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

    Change from baseline to 12 months (Week 52) in Fabry Disease Patient Reported Outcomes (FD-PRO) score, based on FD-PRO total symptom score

    Time frame: Baseline, 12 months (week 52)

07

Study locations

No study locations are listed for this record.

08

References and documents

Individual participant data

Plan to share: Yes — 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://vivli.org

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 7, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT04143958
Lead sponsor
Sanofi
Responsible party
Sponsor
First posted
Oct 30, 2019
Start date
Sep 2020 (estimated)
Primary completion
Nov 2023 (estimated)
Completion
Nov 2023 (estimated)
Last update
Apr 7, 2023

Study contacts

Clinical Sciences & Operations
study director · Sanofi

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is withdrawn, as verified in Apr 2023. You cannot join it, but the record below documents what was studied.

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