Safety, Efficacy, & PK of PRX-102 in Patients With Fabry Disease Administered Intravenously Every 4 Weeks

Launched by PROTALIX · Jun 7, 2017

Keywords

ClinConnect Summary

This is an open-label switchover study to assess the safety, efficacy, and pharmacokinetics of pegunigalsidase alfa treatment of 2 mg/kg every 4 weeks in patients previously treated with enzyme-replacement therapy (ERT): agalsidase alfa or agalsidase beta, for at least 3 years and on a stable dose (\>80% labelled dose/kg) for at least the last 6 months. Following screening, patients will be enrolled and switched from their current ERT to receive intravenous (IV) infusions of pegunigalsidase alfa 2 mg/kg every 4 weeks for 52 weeks (total of 14 infusions). At the time of enrollment, premedica...

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Eligibility criteria

• Key inclusion criteria:
• Eligible subjects must fulfill the following inclusion criteria:
• • 1. Age: 18-60 years
• • 2. A documented diagnosis of Fabry disease
• • 3. Males: plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than lower limit of normal according to the laboratory reference ranges and one or more of the characteristic features of Fabry disease
• • 1. Neuropathic pain
• • 2. Cornea verticillata
• • 3. Clustered angiokeratoma
• • 4. Females: historical genetic test results consistent with Fabry mutations, or in the case of novel mutations a first-degree male relative with Fabry disease, and one or more of the characteristic features of Fabry disease
• • 1. Neuropathic pain
• • 2. Cornea verticillata
• • 3. Clustered angiokeratoma
• • 5. Treatment with agalsidase alfa or agalsidase beta for at least 3 years and on a stable dose (\>80% labelled dose/kg) for at least last 6 months
• • 6. eGFR ≥ 30 mL/min/1.73m\^2 by CKD-EPI equation at screening visit
• • 7. Availability of at least 3 historical serum creatinine evaluations since starting agalsidase alfa or agalsidase beta treatment and not more than 2 years old
• • 8. Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically accepted, highly effective method of contraception. These include combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, or sexual abstinence
• • 9. Patients whose clinical condition, in the opinion of the Investigator, is suitable for treatment with ERT every 4 weeks.
• Key exclusion criteria:
• The presence of any of the following excludes a subject from study enrollment:
• • 1. History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase alfa or agalsidase beta
• • 2. History of renal dialysis or transplantation
• • 3. Linear negative slope of eGFR of ≥ 2 mL/min/1.73m\^2/year based on at least 4 serum creatinine values over approximately 2 years (including the value obtained at the screening visit)
• • 4. 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 post renal obstructive nephropathy)
• • 5. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
• • 6. Urine protein to creatinine ratio (UPCR) at screening \> 0.5 g/g or mg/mg or 500 mg/g and not treated with an ACE inhibitor or ARB
• • 7. Females who are pregnant, planning to become pregnant during the study, or are breast feeding
• • 8. Cardiovascular event (myocardial infarction, unstable angina) in the 6-month period before screening
• • 9. Cerebrovascular event (stroke, transient ischemic attack) in the 6-month period before screening
• • 10. 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.