A Phase 3, Open-label Study to Evaluate the Efficacy and Safety of REPLAGAL® in Treatment-naïve Subjects With Fabry Disease
Overview
- Phase
- Phase 3
- Intervention
- REPLAGAL
- Conditions
- Fabry Disease
- Sponsor
- Shire
- Enrollment
- 17
- Locations
- 28
- Primary Endpoint
- Change From Baseline in Cardiac Structure at Week 104
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
In this study, adults with Fabry Disease who have not had any treatment for this condition will be treated with Replagal. The main aim of the study is to check if Replagal improves kidney function and heart structure of participants with Fabry Disease. Participants will receive one Replagal infusion every other week for up to 104 weeks. They will visit the clinic every 12 to 14 weeks during treatment with a follow-up visit 2 weeks after treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The participant must voluntarily sign an Institutional Review Board (IRB)/Independent Ethics Committee/Research Ethics Board approved informed consent form after all relevant aspects of the study have been explained and discussed with the participant.
- •The participant has Fabry disease as confirmed at screening by the following criteria using a dried blood spot (DBS) assay:
- •For male participants, Fabry disease is confirmed by a deficiency of alpha-galactosidase A (GLA) activity and a mutation in the GLA gene
- •For female participants, Fabry disease is confirmed by a mutation in the GLA gene
- •The participant is 18 to 65 years of age, inclusive.
- •Female participants must have a negative pregnancy test at screening.
- •Female participants of child-bearing potential must agree to use a medically acceptable method of contraception at all times during the study and for at least 14 days after the final study infusion; the methods of acceptable contraception are listed in the protocol.
- •The participant is deemed, as determined by the investigator, to have adequate general health to undergo the specified protocol-related procedures and to have no safety or medical contraindications for participation.
- •The participant has not received any treatment (approved or investigational) specific to Fabry disease, such as enzyme replacement therapy (ERT), chaperone therapy, or substrate reduction therapy.
- •The participant must have an eGFR of 45 to 120 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2); eGFR will be calculated by a Shire-designated laboratory using the CKD-EPI formula. If the eGFR measurement at screening is not within the range, a second eGFR measurement may be completed and, if in range, used as the screening value. If a second measurement is taken, a minimum of 1 week and maximum of 30 days should separate it from the first. This inclusion criterion follows the European Guidelines for Treatment of Fabry Disease and Kidney Disease Improving Global Outcomes guidelines for classification of renal disease.
Exclusion Criteria
- •In the opinion of the investigator, the participant's life expectancy is less than or equal to (\<=) 5 years.
- •The participant has undergone or is scheduled to undergo kidney transplantation or is currently on dialysis, or has any signs or symptoms of end stage renal disease.
- •Urine protein/creatinine ratio (PCR) greater than (\>) 1.5 milligram per milligram (mg/mg).
- •Participants who have clinically relevant history of allergy or signs or symptoms of severe hypersensitivity, (including hypersensitivity to the REPLAGAL active substance or any of the excipients), which in the investigator's judgment, will substantially increase the participant's risk if he or she participates in the study.
- •Cardiac fibrosis involving more than 2 segments, as determined by cMRI at screening.
- •In the opinion of the investigator, the participant has non-Fabry disease-related cause of end-organ (renal, cardiac, central nervous system) dysfunction/failure or is receiving medications that may affect the rate of disease progression, as assessed by cardiac and/or renal measures.
- •The participant has a positive test at screening for hepatitis B surface antigen, positive test for hepatitis B core antibody, positive test for hepatitis C (HCV) antibody with confirmation by HCV-ribonucleic acid polymerase chain reaction testing, or positive test for human immunodeficiency virus antibody.
- •Treatment with REPLAGAL at any time prior to the study.
- •Prior treatment with any of the following medications:
- •FABRAZYME (agalsidase beta) and its biosimilars
Arms & Interventions
REPLAGAL
Participants will receive REPLAGAL 0.2 milligram per kilogram (mg/kg) body weight of intravenous (IV) infusion Every Other Week (EOW) for 104 weeks.
Intervention: REPLAGAL
Outcomes
Primary Outcomes
Change From Baseline in Cardiac Structure at Week 104
Time Frame: Baseline, Week 104
Cardiac structure was planned to be assessed by left ventricular mass index (LVMI) using cardiac magnetic resonance imaging (cMRI). Change from baseline in cardiac structure at Week 104 was planned to be reported.
Change From Baseline in Renal Function at Week 104
Time Frame: Baseline, Week 104
Renal function was planned to be assessed by estimated glomerular filtration rate (eGFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. The eGFR was planned to be calculated by CKD-EPI formula: eGFR = 141 x min (Serum Creatinine \[Scr\]/κ,1)\^(α) x max(Scr/κ,1)\^(-1.209) x 0.993\^(Age) x 1.018 (if female) x 1.159 (if black) where: Scr was serum creatinine (mg/dL); κ was 0.7 for females and 0.9 for males; α was -0.329 for females and -0.411 for males; min indicated the minimum of Scr/κ or 1; max indicated the maximum of Scr /κ or 1. Change from baseline in renal function at Week 104 was planned to be reported.
Secondary Outcomes
- Annualized Rate of Change in Left Ventricular Mass Index (LVMI) up to Week 104(From Baseline up to Week 104)
- Change From Baseline in LVMI up to Week 104(From Baseline up to Week 104)
- Number of Participants With Adverse Events (AEs)(From start of study drug administration up to follow-up visit (i.e., up to Week 106))
- Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) up to Week 104(From Baseline up to Week 104)
- Change From Baseline in eGFR up to Week 104(From Baseline up to Week 104)
- Change From Baseline in Proteinuria up to Week 104(From Baseline up to Week 104)
- Change From Baseline in Plasma Globotriaosylsphingosine (Lyso-Gb3) up to Week 104(From Baseline up to Week 104)
- Change From Baseline in Cardiac Fibrotic Segments up to Week 104(From Baseline up to Week 104)
- Change From Baseline in Interventricular Septal End-Diastolic Thickness and Posterior Wall Thickness in Diastole up to Week 104(From Baseline up to Week 104)
- Number of Participants Who Will Develop Anti-drug Antibodies (ADA) to REPLAGAL(From Baseline up to Week 104)