Study to Evaluate the Safety, PK, PD, and Efficacy of PRX-102 in Japanese Patients With Fabry Disease
- Conditions
- Fabry Disease
- Interventions
- Drug: PRX-102 1 mg/kg every 2 weeksDrug: PRX-102 2 mg/kg every 4 weeks
- Registration Number
- NCT05710692
- Lead Sponsor
- Chiesi Farmaceutici S.p.A.
- Brief Summary
The aim of this study is to evaluate the safety and efficacy of pegunigalsidase alfa in Japanese patients (adults and adolescents) affected by Fabry disease. It is planned of a total of approximately 18-20 male and female Fabry disease patients between the ages of 13 and 60 years to be part of the study. The study is conducted in Japan.
- Detailed Description
Investigators are doing this study to find out if treatment with pegunigalsidase alfa will prevent or reduce the development of health problems caused by Fabry disease and thereby improve patients' health and quality of life.
pegunigalsidase alfa (PRX-102) is a drug made using genetic engineering techniques and manufactured using cultured tobacco cells. It is given by intravenous infusion every 2 weeks, at a dosage of 1 milligram per kilogram (mg/kg) of body weight.
The study consists of a main study that is divided into two stages, each of which will last one year, followed by an optional extension study. In the optional extension stage, the participants may receive PRX-102 intravenous infusion every 2 weeks, at a dosage of 1 milligram per kilogram (mg/kg) of body weight or every 4 weeks at a dosage of 2 milligrams per kilogram (mg/kg) of body weight.
There are three groups (cohorts) in this study, with adults enrolled in either Cohort A or B and adolescents in Cohort C. Whether an adult is assigned to Cohort A or Cohort B depends on their kidney function and treatment history.
This study will start with a screening visit of up to 4 weeks. It will be followed up by infusion visits every 2 weeks or 4 weeks. For subjects not continuing in the extension stage, a follow-up call is to be made 30 days after the last study drug infusion.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 18
Not provided
- Administration of ERT for Fabry disease within 14 days before baseline, substrate reduction therapy for Fabry disease within 3 days before baseline, or chaperone therapy for Fabry disease within 3 days before baseline
- History of 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
- Cohort A only: eGFR value of >90 to ≤120 mL/min/1.73 m2 at screening and a historical eGFR value >120 mL/min/1.73 m2 in the past 9 to 24 months before screening, indicating absence of renal impairment
- 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
- 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.
- Currently taking another investigational drug for any condition
- Carry only known non-pathogenic Fabry mutations
- History of renal dialysis or kidney 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 renal vasculitis); non-specific conditions (e.g., ischemia, toxic injury); as well as extrarenal pathology (e.g., prerenal azotaemia, and acute postrenal obstructive nephropathy
- History of (or current) malignancy requiring treatment; the one exception is a prior history of resected basal cell carcinoma
- Severe cardiomyopathy or significant unstable cardiac disease within 6 months prior to screening
- 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
- 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 30 days after the last study treatment
- Presence of any medical, emotional, behaevioral, or psychological condition that in the judgment of the Investigator could interfere with the subject's compliance with the requirements of the study
- Previous treatment with cellular therapy or gene therapy for any condition
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description PRX-102 1 mg/kg every 2 weeks or PRX-102 2 mg/kg every 4 weeks PRX-102 1 mg/kg every 2 weeks PRX-102 1 mg/kg every 2 weeks or PRX-102 2 mg/kg every 4 weeks (available only in the optional extension part) PRX-102 1 mg/kg every 2 weeks or PRX-102 2 mg/kg every 4 weeks PRX-102 2 mg/kg every 4 weeks PRX-102 1 mg/kg every 2 weeks or PRX-102 2 mg/kg every 4 weeks (available only in the optional extension part)
- Primary Outcome Measures
Name Time Method Change of laboratory tests' results 12 Months, 24 Months and through study completion (an average of 4.5 years) Change in height in centimeters 12 Months, 24 Months and through study completion (an average of 4.5 years) Incidence of Infusion Related Reactions (IRRs) 12 Months, 24 Months and through study completion (an average of 4.5 years) Incidence of Injection site reactions (ISRs) 12 Months, 24 Months and through study completion (an average of 4.5 years) Incidence of premedication use at each visit and change of infusion premedications from baseline 12 Months, 24 Months and through study completion (an average of 4.5 years) Change from baseline of Time to maximum plasma concentration (tmax), pharmacokinetic parameter Assessments will be done over three two-week periods, starting at Baseline (Week 0), V7 (Week 12), and V27 (Week 52) Change from baseline of Area under the plasma concentration-time curve from time 0 to time t (AUC0 t), pharmacokinetic parameter Assessments will be done over three two-week periods, starting at Baseline (Week 0), V7 (Week 12), and V27 (Week 52) Change from baseline of Area under the curve from time 0 to 2 weeks (AUC0-2wk), pharmacokinetic parameter Assessments will be done over three two-week periods, starting at Baseline (Week 0), V7 (Week 12), and V27 (Week 52) Change from baseline of Terminal half-life (t1/2), pharmacokinetic parameter Assessments will be done over three two-week periods, starting at Baseline (Week 0), V7 (Week 12), and V27 (Week 52) Change from baseline of Volume of distribution (Vz), pharmacokinetic parameters Assessments will be done over three two-week periods, starting at Baseline (Week 0), V7 (Week 12), and V27 (Week 52) Incidence of Treatment Emergent Adverse Events (TEAEs) 12 Months, 24 Months and through study completion (an average of 4.5 years) Incidence of treatment-emergent Anti-Drug Antibodies (ADAs) 12 Months, 24 Months and through study completion (an average of 4.5 years) ADA status change from baseline 12 Months, 24 Months and through study completion (an average of 4.5 years) Change from baseline of Area under the curve from time 0 to infinity (AUC0-∞), pharmacokinetic parameter Assessments will be done over three two-week periods, starting at Baseline (Week 0), V7 (Week 12), and V27 (Week 52) Change from baseline of Observed drug concentration at the end of the dosing interval (Cτ), pharmacokinetic parameter Assessments will be done over three two-week periods, starting at Baseline (Week 0), V7 (Week 12), and V27 (Week 52) Change in in body weight in kilograms 12 Months, 24 Months and through study completion (an average of 4.5 years) Change from baseline of Maximum plasma concentration (Cmax), pharmacokinetic parameter Assessments will be done over three two-week periods, starting at Baseline (Week 0), V7 (Week 12), and V27 (Week 52) Change from baseline of Clearance (Cl), pharmacokinetic parameter Assessments will be done over three two-week periods, starting at Baseline (Week 0), V7 (Week 12), and V27 (Week 52) Change from baseline of 12-lead ECG quantitative parameters: Mean Heart Rate, PR Interval, QRS Duration, QT Interval, QTc Interval, and ST Segment 12 Months, 24 Months and through study completion (an average of 4.5 years) Quantitative ECG parameters will be summarized by cohort and overall
Change from baseline of Area under the curve over a dosing interval (AUCτ), pharmacokinetic parameter Assessments will be done over three two-week periods, starting at Baseline (Week 0), V7 (Week 12), and V27 (Week 52) Change in Tanner stage 12 Months, 24 Months and through study completion (an average of 4.5 years) Tanner Staging of Sexual Development will be used to assess sexual development (i.e. breast development (B1 to B5) and pubic hair development (Ph-1 to Ph-5) in females and pubic hair and genetical development (G1-G5) in males.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (9)
Fukuoka University Chikushi Hospital
🇯🇵Chikushino, Fukuoka, Japan
Tohoku University Hospital
🇯🇵Sendai, Miyagi, Japan
University of the Ryukyu Hospital
🇯🇵Nishihara, Okinawa, Japan
Osaka University Hospital
🇯🇵Suita, Osaka, Japan
Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-ku, Tokyo
🇯🇵Bunkyo-ku, Tokyo, Japan
Tokyo Jikei University Hospital
🇯🇵Minato-ku, Tokyo, Japan
Keio University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
Asahikawa Medical University Hospital
🇯🇵Asahikawa City, Japan
Niigata University Medical & Dental Hospital
🇯🇵Niigata, Japan