Fabry Disease
Conditions
Keywords
Biosimilar, Fabry disease, Fabry, agalsidase beta, Switch over
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 serum Lyso-Gb3 marker ratio after 26 weeks of treatment, defined as serum level of the marker Lyso-Gb3 after 26 weeks (6 months) divided by serum level of the marker Lyso-Gb3 at baseline).
Interventions
DRUGRecombinant human alpha galactosidase A (agalsidase beta)
All participants will receive 2 doses of Fabrazyme® with approximately 14 days between them. The dose will be 1 mg/kg of body mass every 2 weeks
DRUGRecombinant human alpha-galactosidase A (agalsidase beta)
All participants will receive AGA BETA BS for 54 weeks. The dose will be 1 mg/kg of body mass every 2 weeks
Sponsors
Bio Sidus SA
Amsterdam UMC
IQVIA Solutions
IQVIA RDS Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model 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®.
Eligibility
Sex/Gender
ALL
Age
16 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Sex and Age 1. Male or female participant with ≥16 and ≤60 years of age at the time of signing the informed consent form (ICF). Reproduction 2. 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. 3. 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). 4. 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. 5. Male participants who are not considering fathering a child during the study and for 3 months after the last dose of study treatment. 6. 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. 7. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 8. Confirmed previous diagnosis of FD. 1. Women: preferably present genetic testing showing pathogenic GLA mutation consistent with FD at screening. 2. Men: preferably present leukocyte α-Gal A activity below normal range and/ or pathogenic GLA mutation consistent with FD at screening. 3. Male with classic FD phenotype, female with classic FD and men with late onset may be included. 9. Participants who have been on stable Fabrazyme® treatment for at least 6 months prior to Baseline visit. 10. 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. 11. Disease status considered clinically stabilized, at Investigators' discretion. 12. Estimated glomerular filtration rate (eGFR) ≥45 mL/minute/1.73 m2 by CKD-EPI equation at Screening visit. 13. 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.
Exclusion criteria
1. Chronic kidney disease in stage 3b, 4, or 5. 2. History of dialysis, kidney transplant or participants who are on the waiting list for a kidney transplant. 3. Proteinuria ≥1 g/day at screening. 4. Participants who have suffered a clinical cardiovascular event (such as but not limited to myocardial infarction, transient ischemic attack) within 6 months prior to 5. 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). 6. 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. 7. History of anaphylaxis or other type I hypersensitivity reactions to agalsidase beta. 8. 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). 9. 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. 10. Treatment initiation or change of dose of ACE inhibitors or ARBs in the 4 weeks before the screening. 11. Current participation in an interventional study, in which the participant received any drug within 90 days before the Screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Lyso Gb3 Serum Levels | Baseline (after 5 week lead-in period on Fabrazyme®) and 26 weeks (after the switch to AGA BETA BS) | 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 serum Lyso-Gb3 marker ratio after 26 weeks of treatment, defined as serum level of the marker Lyso-Gb3 after 26 weeks (6 months) divided by serum level of the marker Lyso-Gb3 at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Lyso-Gb3 Serum Levels | Baseline (after 5 week lead-in period on Fabrazyme®) and 54 weeks (after the switch to AGA BETA BS) | To evaluate the difference in efficacy between AGA BETA BS and Fabrazyme® after 1 year (54 weeks) of treatment in participants with Fabry disease previously stabilized with Fabrazyme®, by measuring disease biomarker. Endpoint: Mean serum Lyso-Gb3 marker ratio after 54 weeks of treatment, defined as serum level of the marker Lyso-Gb3 after 54 weeks (12 months) divided by serum level of the marker Lyso-Gb3 at baseline. |
| Change From Baseline in Pain Severity as Assessed by Brief Pain Inventory-short Form Pain Severity Items Scores | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). | 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 Brief Pain Inventory-short form (BPI). The Brief Pain Inventory (BPI) is a validated patient-reported outcome instrument assessing pain severity and pain-related interference with daily activities. Pain severity is assessed using four items rated on a 0-10 numeric rating scale (0 = no pain; 10 = pain as bad as imaginable), with the score calculated as the mean of items (range 0-10; higher scores indicate worse pain). Pain interference is assessed using seven items rated on a 0-10 numeric rating scale (0 = does not interfere; 10 = completely interferes), with the score calculated as the mean of items (range 0-10; higher scores indicate worse outcome). Endpoint: Change from baseline in pain severity as assessed by BPI-short form pain severity items scores after 26 and 54 weeks of treatment. |
| Change From Baseline in Pain Interference as Assessed by BPI-short Form Pain Interference Items Scores | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). | 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. The Brief Pain Inventory (BPI) is a validated patient-reported outcome instrument assessing pain severity and pain-related interference with daily activities. Pain severity is assessed using four items rated on a 0-10 numeric rating scale (0 = no pain; 10 = pain as bad as imaginable), with the score calculated as the mean of items (range 0-10; higher scores indicate worse pain). Pain interference is assessed using seven items rated on a 0-10 numeric rating scale (0 = does not interfere; 10 = completely interferes), with the score calculated as the mean of items (range 0-10; higher scores indicate worse outcome). Endpoint: Change from baseline in pain severity as assessed by BPI-short form pain severity items scores after 26 and 54 weeks of treatment. |
| Change From Baseline in SF-36 Health Survey Scores | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). | 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 Short Form-36 Health Survey (SF-36). The Short Form-36 Health Survey (SF-36) is a validated patient-reported outcome instrument consisting of 36 questions designed to assess health-related quality of life. The questionnaire generates scores across eight domains (physical functioning, role limitations due to physical health, pain, general health, energy/fatigue, social functioning, role limitations due to emotional problems, and emotional well being), each scored on a 0-100 scale. Domain scores are calculated according to standard scoring algorithms, with higher scores indicating better health status and quality of life. Endpoint: Change from baseline in SF-36 scores after 26 and 54 weeks of treatment. |
| Mean Blood Urea Nitrogen (BUN) Levels at Specified Timepoints | Baseline (after 5 week lead-in period on Fabrazyme®), 14 weeks, 26 weeks and 54 weeks (after the switch to AGA BETA BS). | — |
| Mean Estimated Glomerular Filtration Rate (eGFR) at Specified Timepoints | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). | — |
| Mean Urine Albumin-to-Creatinine Ratio at Specified Timepoints | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). | — |
| Mean Electrolyte and Phosphate Levels at Specified Timepoints | Baseline (after 5 week lead-in period on Fabrazyme®), 14 weeks, 26 weeks and 54 weeks (after the switch to AGA BETA BS). | — |
| Mean Heart Rate From Electrocardiogram Assessments at Specified Timepoints | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). | Evaluation of Heart Rate based on the analysis of electrocardiogram exams performed at baseline, 26 weeks and 54 weeks. |
| Mean PR, QRS, QT, QTcB, and QTcF Intervals at Specified Timepoints | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). | Evaluation of PR, QRS, QT , QTcB and QTcF intervals based on the analysis of electrocardiogram exams performed at baseline, 26 weeks and 54 weeks. |
| Mean Left Ventricular Wall Thickness at Specified Timepoints | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). | Evaluation of cardiac function based on the analysis of bidimensional echocardiogram exams performed at baseline, 26 weeks and 54 weeks. |
| Mean Left Ventricular Mass Index at Specified Timepoints | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). | Evaluation of cardiac function based on the analysis of bidimensional echocardiogram exams performed at baseline, 26 weeks and 54 weeks. |
| Mean Left Ventricular Ejection Fraction at Specified Timepoints | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). | Evaluation of cardiac function based on the analysis of bidimensional echocardiogram exams performed at baseline, 26 weeks and 54 weeks. |
| Number of Participants With Positive Neutralizing Antibodies at Specified Timepoints | Baseline (after 5 week lead-in period on Fabrazyme®),14 weeks, 26 weeks and 54 weeks (after the switch to AGA BETA BS). | Count of participants whose serum samples showed a neutralization percentage of agalsidase beta activity greater than 50%, the predefined threshold indicating a positive result for neutralizing antibodies. Neutralizing antibody activity was evaluated using blood samples collected at Baseline, Week 14, Week 26, and Week 54. Participants with neutralization values exceeding the 50% cutoff were classified as positive for neutralizing antibodies at each timepoint. |
Countries
Argentina
Contacts
PRINCIPAL_INVESTIGATORAlberto A Fernández, MD
Instituto de Investigaciones Clínicas Quilmes
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 35.6 years STANDARD_DEVIATION 12.6 |
| BMI | 26.4 Kg/m2 STANDARD_DEVIATION 6.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fabry disease Phenotype Classic Female | 15 Participants |
| Fabry disease Phenotype Classic Male | 5 Participants |
| Fabry disease Phenotype Late Onset Female | 0 Participants |
| Fabry disease Phenotype Late Onset Male | 0 Participants |
| Height | 162.2 Centimeters STANDARD_DEVIATION 7.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment Argentina | 20 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 5 Participants |
| Weight | 69.9 Kilograms STANDARD_DEVIATION 15.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 19 |
| other Total, other adverse events | 4 / 20 | 17 / 19 |
| serious Total, serious adverse events | 0 / 20 | 5 / 19 |
Outcome results
None listed