Study to Evaluate the Safety, PK, PD, and Efficacy of PRX-102 in Japanese Patients With Fabry Disease
- Conditions
- Fabry disease
- Registration Number
- JPRN-jRCT2031230079
- Lead Sponsor
- Simona Amore
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 18
Subjects must meet all of the following inclusion criteria to be eligible for enrolment in the study:
All subjects
1. Must have been born in Japan and have their biological parents and all 4 grandparents of Japanese descent
2. A documented diagnosis of Fabry disease, as determined by the following:
- Males: Plasma and/or leukocyte alfa-galactosidase-A activity (by activity assay) that is =<5% of mean normal laboratory levels, or, if the enzymatic activity is above the 5% limit but still under the normal level, a confirmed disease-causing mutation of the GLA gene
- Females: Historical genetic test results consistent with Fabry mutations, or, in the case of novel mutations, a first-degree male relative with Fabry disease
- All subjects: At least one of the following characteristic features of Fabry disease: neuropathic pain, cornea verticillata, and/or clustered angiokeratoma
3. Estimated glomerular filtration rate (eGFR) at screening =>40 mL/min/1.73 m^2. For adults, this will be calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine equation (2009); and for adolescents, it will be calculated using the Creatinine Cystatin C-based Chronic Kidney Disease in Children (CKiD) equation.
4. Clinical condition that in the opinion of the Investigator requires treatment with ERT
5. A female subject (including an adolescent in Cohort C, if applicable) must meet one of the following criteria:
- If of childbearing potential, she must:
a. Have a negative serum pregnancy test result at screening, AND
b. Agree to undergo a urine pregnancy test at baseline and every 12 weeks thereafter up to the final treatment, AND
c. Agree to use one of the following highly reliable methods of contraception from the day of the informed consent signature until 30 days after the last infusion received. The following methods are acceptable:
- Placement of an intrauterine device (IUD) or intrauterine releasing system (IUS)
- Combined (both estrogen and progestogen) hormonal contraception (oral) associated with inhibition of ovulation, supplemented with a barrier method (preferably male condom)
- Bilateral tubal occlusion
- Sexual abstinence, defined as refraining from heterosexual intercourse during the entire study period
- Partner vasectomy, provided that the partner is the sole sexual partner and has received medical verification of the surgical success
Be of non-childbearing potential, defined as one of the following:
- Post-menopausal (12 consecutive months of amenorrhea), OR
- Permanently sterile following hysterectomy, bilateral salpingectomy, or bilateral oophorectomy (supporting evidence required)
Additional inclusion criteria for subjects in Cohort A
- Aged =>18 to =< 60 years
- Treatment with agalsidase beta for at least the last 12 months, with the dose stable (defined as having received at least 80% of the labelled dose) for at least the last 6 months
- Diagnosis of kidney impairment, defined as a linear slope of eGFR more negative or equal to -2 mL/min/1.73 m~2/year. The historical slope will be calculated based on at least 3 serum creatinine values obtained over the past 9 to 24 months prior to screening, using the CKD-EPI Creatinine equation (2009). It is preferable if all 3 samples assessed were done at the same center using the same laboratory; however, the results of samples that were assessed by different laboratories will be accepted. This criterion will be confirmed at screening by calculating the screening eGFR
The presence of any of the following will exclude a prospective subject from study enrolment:
1. Administration of previous treatment for Fabry disease within 14 days before baseline or chaperone therapy for Fabry disease within 3 days before baseline
2. History of severe type I hypersensitivity reactions (anaphylactic or anaphylactoid life-threatening reaction) to other ERT treatment for Fabry disease or to any component of the study drug
3. Cohort A only: eGFR value of >90 to =<120 mL/min/1.73 m^2 at screening, and a historical eGFR value >120 mL/min/1.73 m^2 in the past 9 to 24 months before screening, indicating absence of renal impairment
4. Urine protein to creatinine ratio (UPCR) >0.5 g/g (0.5 mg/mg or 500 mg/g) if not treated with an ACE inhibitor or ARB
5. Initiation of treatment, or a change in dose to ongoing treatment, with an angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in the 4 weeks prior to screening
6. Currently taking another investigational drug for any condition
7. Known non-pathogenic Fabry mutations
8. History of renal dialysis or kidney transplantation
9. History of acute kidney injury in the 12 months prior to screening, including specific kidney diseases (e.g., acute interstitial nephritis, acute glomerular and renal vasculitis); non-specific conditions (e.g., ischemia, toxic injury); as well as extrarenal pathology (e.g., prerenal azotemia, and acute postrenal obstructive nephropathy
10. History of (current) malignancy requiring treatment; the one exception is a prior history of resected basal cell carcinoma
11. Severe cardiomyopathy or significant unstable cardiac disease within 6 months prior to screening
12. A positive test for Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) within 3 months prior to Screening, using a validated molecular assay or validated antigen assay
13. Females: Pregnant or lactating or of childbearing potential with a fertile male partner and unwilling to use a highly reliable method of contraception from the informed consent signature until study participation ends
14. Presence of any medical, emotional, behavioral, or psychological condition that in the judgment of the Investigator could interfere with the subject compliance with the requirements of the study
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method