Fabry DiseasePhase 4BCLEAR1NCT04143958
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 study testing agalsidase beta (GZ419828) and agalsidase alfa in people with Fabry Disease, run by Sanofi.
Trial 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… Read more about this study
- Who is it for?
- Ages 16 to 45 years, men only
- Conditions the study is for
- Fabry Disease
- What is being tested?
- agalsidase beta (GZ419828) and agalsidase alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2020to Nov 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 45 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
About this study
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
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).
- Conditions
- Fabry Disease
- Being tested
- agalsidase beta (GZ419828), agalsidase alfa
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
agalsidase beta (GZ419828)Drug
Pharmaceutical form:Powder for concentrate for solution for infusion Route of administration: Intravenous (IV) infusion,
agalsidase alfaDrug
Pharmaceutical form:concentrate for solution for infusion Route of administration: Intravenous (IV) infusion
| Study group | Role | What they receive |
|---|---|---|
| agalsidase beta | Experimental | Commercially available agalsidase beta treatment at approved dose and regimen;administered once every 2 weeks as an IV infusion Receives: Drug: agalsidase beta (GZ419828) |
| agalsidase alfa | Active comparator | Commercially available agalsidase alfa treatment at approved dose and regimen; administered once every 2 weeks as an IV infusion Receives: Drug: agalsidase alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Plasma globotriaosylsphingosine (lyso-GL3) level
Change from baseline to 12 months (week 52) for plasma lyso-GL3 level
Measured: Baseline, 12 months (week 52)
Secondary outcomes (6)
Change in GL3 content in podocytes
Change from baseline to 12 months (week 52) for GL3 content in podocytes
Measured: Baseline, 12 months (week 52)
Change in GL3 content in endothelial skin cells
Change from baseline to 12 months (Week 52) for GL3 content in endothelial skin cells
Measured: Baseline, 12 months (week 52)
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)
Measured: Baseline, 12 months (week 52)
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]
Measured: Baseline, 12 months (week 52)
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
Measured: Baseline, 12 months (week 52)
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
Measured: Baseline, 12 months (week 52)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2019
- Study startSep 2020 (estimated)
- Primary completionNov 2023 (estimated)
- Study completionNov 2023 (estimated)
Why it stopped: The Sponsor terminated the study due to recruitment infeasibility without having enrolled any patient.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04143958
- Sponsor's protocol ID
- LPS15918
- Other IDs
- 2019-000064-21, U1111-1223-5105, 2019
- Acronym
- BCLEAR1
- Status last verified
- Apr 2023
- First submitted
- 28 Oct 2019
- Last updated
- 7 Apr 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04143958
- Acronym / sponsor ID
- BCLEAR1 / LPS15918
- Conditions
- Fabry Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The Sponsor terminated the study due to recruitment infeasibility without having enrolled any patient.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Sep 2020 (estimated)
- Primary completion
- Nov 2023 (estimated)
- Study completion
- Nov 2023 (estimated)
- First posted
- 30 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| agalsidase beta | Experimental | Drug: agalsidase beta (GZ419828)Commercially available agalsidase beta treatment at approved dose and regimen;administered once every 2 weeks as an IV infusion |
| agalsidase alfa | Active comparator | Drug: agalsidase alfaCommercially available agalsidase alfa treatment at approved dose and regimen; administered once every 2 weeks as an IV infusion |
Who may qualify
- Ages
- 16 to 45 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| agalsidase beta (GZ419828)Pharmaceutical form:Powder for concentrate for solution for infusion Route of administration: Intravenous (IV) infusion, | Drug | agalsidase beta |
| agalsidase alfaPharmaceutical form:concentrate for solution for infusion Route of administration: Intravenous (IV) infusion | Drug | agalsidase alfa |
Primary outcome
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
6 secondary outcomes
Change in GL3 content in podocytes
Time frame: Baseline, 12 months (week 52)
Change in GL3 content in endothelial skin cells
Time frame: Baseline, 12 months (week 52)
Change in measured glomerular filtration rate (mGFR)
Time frame: Baseline, 12 months (week 52)
Change in estimated glomerular filtration rate (eGFR) calculated
Time frame: Baseline, 12 months (week 52)
Change in Mainz Severity Score Index (MSSI) total score
Time frame: Baseline, 12 months (week 52)
Change in Fabry Disease Patient Reported Outcomes (FD-PRO) total symptom score
Time frame: Baseline, 12 months (week 52)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2023.
- Individual participant dataSharing planned: 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing agalsidase beta (GZ419828) and agalsidase alfa in people with Fabry Disease, run by Sanofi.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 7 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Plasma globotriaosylsphingosine (lyso-GL3) level (time frame: Baseline, 12 months (week 52)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2023.