Study of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function (BALANCE)

Protalix BioTherapeutics

Status and phase: Completed; Phase 3

Conditions: Fabry Disease

Treatments: Biological: agalsidase beta; Biological: PRX-102 (pegunigalsidase alfa)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02795676

PB-102-F20

Details and patient eligibility

About

This was a randomized, double-blind, active control study of the enzyme replacement therapy (ERT) drug PRX-102 (pegunigalsidase alfa) in Fabry disease patients with impaired renal function. Patients who had been treated for approximately 1 year with agalsidase beta and who had been on a stable dose of that product for at least 6 months were randomized in a 2:1 ratio to either switch to PRX-102 or to continue treatment with agalsidase beta. Both treatments were delivered by intravenous infusions every two weeks, at a dosage of 1 mg/kg.

Full description

This was a randomized, double-blind, active control study examining the safety and efficacy of pegunigalsidase alfa (PRX-102) in Fabry disease patients with impaired renal function. Participants had to have been taking the licensed ERT drug agalsidase beta (Fabrazyme®) for at least 1 year prior to study entry, and to have been on a stable dose of that product for at least the last 6 months. Since the disease expresses itself differently in males and females, gender could have an impact on the therapeutic effect; thus, there was additionally a requirement that no more than 50% of the patients could be female.

Following screening, eligible patients were randomized in a 2:1 ratio to either switch to PRX-102 or continue treatment with agalsidase beta, with randomization stratified according to whether the urine protein-to-creatinine ratio (UPCR), a measure of kidney function, was above or below a specified threshold. Both products were administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg, for up to 24 months. Both patients and study staff were blinded as to which treatment was being given.

Patients who completed the study were invited to continue in a long-term open-label extension study, PB-102-F60, in which all participants would receive PRX-102 1 mg/kg every 2 weeks.

Enrollment: 78 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Symptomatic adult Fabry disease patients, age 18-60 years

  1. Males: Plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than 30% mean normal levels and one or more of the characteristic features of Fabry disease

     i. neuropathic pain

     ii. cornea verticillata

     iii. clustered angiokeratoma

  2. Females:

     a. historical genetic test results consistent with Fabry pathogenic mutation and one or more of the described characteristic features of Fabry disease:

     i. neuropathic pain

     ii. cornea verticillata

     iii. clustered angiokeratoma

     b. or in the case of novel mutations a first degree male family member with Fabry disease with the same mutation, and one or more of the characteristic features of Fabry disease

     i. neuropathic pain

     ii. cornea verticillata

     iii. clustered angiokeratoma

• Screening eGFR by CKD-EPI equation 40 to 120 mL/min/1.73 m²

• Linear negative slope of eGFR based on at least 3 serum creatinine values over approximately 1 year (range of 9 to 18 months, including the value obtained at the screening visit) of ≥ 2 mL/min/1.73 m²/year

• Treatment with a dose of 1 mg/kg agalsidase beta per infusion every 2 weeks for at least one year and at least 80% of 13 (10.4) mg/kg total dose over the last 6 months.

• Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically accepted method of contraception, not including the rhythm method.

Exclusion criteria

• History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase beta
• Known non-pathogenic Fabry mutations
• History of renal dialysis or transplantation
• History of acute kidney injury in the 12 months prior to screening, including specific kidney diseases (e.g., acute interstitial nephritis, acute glomerular and vasculitic renal diseases); non-specific conditions (e.g, ischemia, toxic injury); as well as extrarenal pathology (e.g., prerenal azotemia, and acute postrenal obstructive nephropathy)
• Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
• Patient with a screening eGFR value between 91-120 mL/min/1.73 m², having an historical eGFR value higher than 120 mL/min/1.73 m² (during 9 to 18 months before screening)
• Urine protein to creatinine ratio (UPCR) > 0.5 g/g and not treated with an ACE inhibitor or ARB
• Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before randomization
• Congestive heart failure NYHA Class IV
• Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before randomization
• Known history of hypersensitivity to Gadolinium contrast agent that is not managed by the use of pre-medication
• Female subjects who are pregnant, planning to become pregnant during the study, or are breastfeeding
• Presence of any medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator and/or Medical Director, would interfere with the patient's compliance with the requirements of the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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78 participants in 2 patient groups

PRX-102 (pegunigalsidase alfa)

Experimental group

Description:

PRX-102 infusion every 2 weeks

Treatment:

Biological: PRX-102 (pegunigalsidase alfa)

agalsidase beta

Active Comparator group

Description:

agalsidase beta infusion every 2 weeks

Treatment:

Biological: agalsidase beta