Switch Over Study of Biosimilar AGA for Fabry Disease
- Conditions
- Fabry Disease
- Interventions
- Drug: Recombinant human alpha galactosidase A (agalsidase beta)Drug: Recombinant human alpha-galactosidase A (agalsidase beta)
- Registration Number
- NCT05843916
- Lead Sponsor
- Bio Sidus SA
- Brief Summary
BIO-AGA-Fase III-001 is a Phase III, prospective, multicenter, open-label, single-group, baseline-controlled, switch over clinical trial to evaluate the efficacy and safety of AGA BETA BS in patients with FD already treated and previously stabilized with Fabrazyme®.
- Detailed Description
BIO-AGA-Fase III-001 is a Phase III, prospective, multicenter, open-label, single-group, baseline-controlled, switch over clinical trial to evaluate the efficacy and safety of AGA BETA BS in patients with FD already treated and previously stabilized with Fabrazyme®.
The study will be conducted in 2 parts: a 5-week Lead-in period (period 1) and 54 week treatment period (period 2). During period 1 all participants will receive 2 intravenous (IV) infusions of Fabrazyme®, provided by Biosidus. After that, in period 2 all participants will switch treatment to AGA BETA BS.
A total of up to 20 participants are planned for the study.
•The primary objective of the study is to evaluate the equivalence in efficacy between AGA BETA BS and Fabrazyme® after 6 months of treatment in participants with Fabry disease previously stabilized with Fabrazyme, by measuring disease biomarker (mean plasma Lyso-Gb3 marker ratio after 26 weeks of treatment, defined as plasma level of the marker Lyso-Gb3 after 26 weeks (6 months) divided by plasma level of the marker Lyso-Gb3 at baseline).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 20
Sex and Age
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Male or female participant with ≥18 and ≤60 years of age at the time of signing the informed consent form (ICF).
Reproduction
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Female participants who are not pregnant, breastfeeding, donating eggs (ova, oocytes), or considering becoming pregnant during the study and for 3 months after the last dose of study treatment.
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All women of childbearing potential (WOCBP) must have a negative urine pregnancy test at the Screening visit and at Baseline visit (prior to the first dose of experimental intervention).
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WOCBP must use one highly effective form of birth control contraception through the study and for 3 months after the last dose of study treatment (refer to Appendix 1 in Section 10.1).
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Male participants who are not considering fathering a child during the study and for 3 months after the last dose of study treatment.
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Male sexually active participant with female partner(s) of childbearing potential must agree to use male condoms during the study and for 3 months after the last dose of study treatment or have documented successful surgical sterilization.
Informed Consent
-
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Type of Participant and Characteristics
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Confirmed previous diagnosis of FD.
- Women: preferably present genetic testing showing pathogenic GLA mutation consistent with FD at screening.
- Men: preferably present leukocyte α-Gal A activity below normal range and/ or pathogenic GLA mutation consistent with FD at screening.
- At least 50% of the participants will be male with classic FD phenotype. The remaining percentage will consist of male late onset and classic women FD phenotype.
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Participants who have been on stable Fabrazyme® treatment for at least 6 months prior to Baseline visit.
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Patients that in the last 3 months before the baseline visit have been receiving ≥80% of Fabrazyme®'s labeled dose/kg, this calculation includes both infusions provided by Biosidus during the Lead in period.
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Disease status considered clinically stabilized, at Investigators' discretion.
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Estimated glomerular filtration rate (eGFR) ≥45 mL/minute/1.73 m2 by CKD-EPI equation at Screening visit.
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If receiving pain killers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), participants must be in a stable dose for ≥ 4 weeks.
Medical Conditions
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Chronic kidney disease in stage 3b, 4, or 5.
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History of dialysis, kidney transplant or participants who are on the waiting list for a kidney transplant.
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Proteinuria ≥1 g/day at screening.
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Participants who have suffered a clinical cardiovascular event (such as but not limited to myocardial infarction, transient ischemic attack) within 6 months prior to Screening visit.
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Participants who have clinically significant unstable cardiac disease (such as but not limited to uncontrolled symptomatic arrhythmia, unstable angina, congestive heart failure New York Heart Association class III or IV).
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Participants who have suffered a clinical cerebrovascular event (such as but not limited to stroke, transient ischemic attack) within 6 months prior to Screening visit.
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History of anaphylaxis or other type I hypersensitivity reactions to agalsidase beta.
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History of acute kidney injury in the 12 months prior to Screening visit (such as but not limited to acute interstitial nephritis, acute renal failure of glomerular origin or caused by vasculitis).
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Presence of any medical, emotional, behavioral, or psychological condition that, according to the Investigator, would interfere with the participant's compliance with the requirements of the study.
Prior/Concomitant Therapy
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Treatment initiation or change of dose of ACE inhibitors or ARBs in the 4 weeks before the screening.
Prior/Concurrent Clinical Trial Experience
-
Current participation in an interventional study, in which the participant received any drug within 90 days before the Screening visit.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AGA BETA BS Recombinant human alpha galactosidase A (agalsidase beta) The study has a single-arm. First, all participants will receive 2 doses of Fabrazyme® with approximately 14 days between them, and afterwards all participants will switch treatment and receive AGA BETA BS for 54 weeks AGA BETA BS Recombinant human alpha-galactosidase A (agalsidase beta) The study has a single-arm. First, all participants will receive 2 doses of Fabrazyme® with approximately 14 days between them, and afterwards all participants will switch treatment and receive AGA BETA BS for 54 weeks
- Primary Outcome Measures
Name Time Method Equivalence in efficacy between AGA BETA BS and Fabrazyme® after 6 months of treatment 6 months • The primary objective of the study is to evaluate the equivalence in efficacy between AGA BETA BS and Fabrazyme® after 6 months of treatment in participants with Fabry disease previously stabilized with Fabrazyme, by measuring disease biomarker. Endpoint: • Mean plasma Lyso-Gb3 marker ratio after 26 weeks of treatment, defined as plasma level of the marker Lyso-Gb3 after 26 weeks (6 months) divided by plasma level of the marker Lyso-Gb3 at baseline.
- Secondary Outcome Measures
Name Time Method To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of hematocrit 54 weeks Hematocrit at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of mean corpuscular volume 54 weeks Mean corpuscular volume at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of white blood cell count 54 weeks White blood cell count at 54 weeks
Compare the impact of pain on daily functions before and after 54 weeks of treatment with AGA BETA 54 weeks • To compare the impact of pain on daily functions before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the BPI (Brief Pain Inventory)-short form. Endpoint: • Change from baseline in pain interference as assessed by BPI-short form pain interference items scores after 54 weeks of treatment
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of %reticulocytes 54 weeks %reticulocytes at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of chlorine 54 weeks Chlorine at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of red blood cell count after 26 weeks of treatment 26 weeks Red blood cell count at 26 weeks
Difference in efficacy between AGA BETA BS and Fabrazyme® after 1 year of treatment 1 year • To evaluate the difference in efficacy between AGA BETA BS and Fabrazyme® after 1 year of treatment in participants with Fabry disease previously stabilized with Fabrazyme®, by measuring disease biomarker. Endpoint: • Mean plasma Lyso-Gb3 marker ratio after 54 weeks of treatment, defined as plasma level of the marker Lyso-Gb3 after 54 weeks (12 months) divided by plasma level of the marker Lyso-Gb3 at baseline.
Compare the pain severity before and after 26 weeks of treatment with AGA BETA BS 26 weeks • To compare the pain severity before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the BPI (Brief Pain Inventory)-short form. Endpoint: • Change from baseline in pain severity as assessed by BPI-short form pain severity items scores after 26 of treatment.
Compare the pain severity before and after 54 weeks of treatment with AGA BETA BS 54 weeks • To compare the pain severity before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the BPI (Brief Pain Inventory)-short form. Endpoint: • Change from baseline in pain severity as assessed by BPI-short form pain severity items scores after 54 weeks of treatment.
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of red blood cell count after 14 weeks of treatment 14 weeks Red blood cell count at 14 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of red blood cell count after 54 weeks of treatment 54 weeks Red blood cell count at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of hemoglobin after 14 weeks of treatment 14 weeks Hemoglobin at 14 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of hemoglobin after 26 weeks of treatment 26 weeks Hemoglobin at 26 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of mean corpuscular hemoglobin 54 weeks Mean corpuscular hemoglobin at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of neutrophils 54 weeks Neutrophils at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of lymphocytes 54 weeks Lymphocytes at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of monocytes 54 weeks Monocytes at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of eosinophils 54 weeks Eosinophils at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of basophils 54 weeks Basophils at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of blood urea nitrogen 54 weeks Blood urea nitrogen at 54 weeks
Compare the impact of pain on daily functions before and after 26 weeks of treatment with AGA BETA 26 weeks • To compare the impact of pain on daily functions before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the BPI (Brief Pain Inventory)-short form. Endpoint: • Change from baseline in pain interference as assessed by BPI-short form pain interference items scores after 26 weeks of treatment
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of platelet count after 26 weeks of treatment. 26 weeks Platelet count at 26 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of red blood cell count at baseline. Baseline Red blood cell count at baseline
Compare the participants' perception of their own health before and after 26 weeks of treatment with AGA BETA BS 26 weeks • To compare the participants' perception of their own health before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the SF (Short Form)-36. Endpoint: • Change from baseline in SF-36 scores after 26 weeks of treatment.
Compare the participants' perception of their own health before and after 54 weeks of treatment with AGA BETA BS 54 weeks • To compare the participants' perception of their own health before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the SF (Short Form)-36. Endpoint: • Change from baseline in SF-36 scores after 54 weeks of treatment.
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of platelet count at baseline. Baseline Platelet count at baseline
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of platelet count after 14 weeks of treatment. 14 weeks Platelet count at 14 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of platelet count after 54 weeks of treatment. 54 weeks Platelet count at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of hemoglobin at baseline Baseline Hemoglobin at baseline
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of hemoglobin after 54 weeks of treatment 54 weeks Hemoglobin at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of phosphate 54 weeks Phosphate at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of creatinine 54 weeks Creatinine at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of cholesterol LDL 54 weeks Cholesterol LDL at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of mean cell hemoglobin concentration 54 weeks Mean cell hemoglobin concentration at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of total cholesterol 54 weeks Total cholesterol at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of cholesterol HDL 54 weeks Cholesterol HDL at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of direct bilirrubin 54 weeks Direct bilirrubin at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of triglycerides 54 weeks Triglycerides at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of glycemia 54 weeks Glycemia at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of total bilirrubin 54 weeks Total bilirrubin at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of aspartate aminotransferase 54 weeks Aspartate aminotransferase at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of alanine aminotransferase 54 weeks Alanine aminotransferase at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of sodium 54 weeks Sodium at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of alkaline phosphatase 54 weeks Alkaline phosphatase at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of albumin 54 weeks Albumin at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of Gamma glutamyl transferase 54 weeks Gamma glutamyl transferase at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of estimated Glomerular Filtration Rate 54 weeks estimated Glomerular Filtration Rate at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of urine albumin-creatinine ratio 54 weeks Urine albumin-creatinine ratio at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the general evaluation of first morning urine 54 weeks First morning urine at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® regarding cardiac function through the evaluation of electrocardiograms. 54 weeks General evaluation of cardiac function based on the analysis of electrocardiogram exam performed after 54 weeks of treatment.
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of anti-AGA levels from blood samples. 54 weeks Evaluation of immunogenicity based on the analysis of anti-AGA levels from blood samples collected at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the analysis of physical assessments, adverse events and infusion-related reactions. 54 weeks Analysis of data obtained from clinical and physical assessments, and from reported adverse events and infusion-related reactions throughout the clinical trial. This outcome will be measured in terms of Presence/Absence of relevant clinical findings.
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of potassium 54 weeks Potassium at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of bicarbonate 54 weeks Bicarbonate at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of magnesium 54 weeks Magnesium at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of calcium 54 weeks Calcium at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® through the evaluation of total proteins 54 weeks Total proteins at 54 weeks
To characterize the safety of AGA BETA BS treatment in participants with Fabry disease previously stabilized with Fabrazyme® regarding cardiac function through the evaluation of echocardiograms. 54 weeks Evaluation of cardiac function based on the analysis of bidimensional echocardiogram exams performed after 54 weeks of treatment.
Trial Locations
- Locations (4)
Instituto de Nefrología Pergamino S.R.L
🇦🇷Pergamino, Buenos Aires, Argentina
Centro Médico Santa María de la Salud
🇦🇷San Isidro, Buenos Aires, Argentina
Instituto de Investigaciones Clínicas Quilmes
🇦🇷Buenos Aires, Argentina
Clínica Universitaria Reina Fabiola
🇦🇷Córdoba, Argentina