Study to Evaluate the Safety, PK, PD, and Efficacy of PRX-102 in Japanese Patients With Fabry Disease

NCT05710692 | Recruiting Phase 2

• 1 other identifier: CLI-06657AA2-01
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 10

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 16 male and female Fabry disease patients between the ages of 13 and 70 years to be part of the study. The study is conducted in Japan.

Conditions

Fabry Disease

Outcome Measures

Primary Outcomes (21)

• Incidence of Treatment Emergent Adverse Events (TEAEs)

  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)

• Change of laboratory tests' results

  12 Months, 24 Months and through study completion (an average of 4.5 years)

• Change in in body weight in kilograms

  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)

• Change in Tanner stage

  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.

  12 Months, 24 Months and through study completion (an average of 4.5 years)

• Change from baseline of 12-lead ECG quantitative parameters: Mean Heart Rate, PR Interval, QRS Duration, QT Interval, QTc Interval, and ST Segment

  Quantitative ECG parameters will be summarized by cohort and overall

  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)

• 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 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 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 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 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 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 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 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 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)

Other Outcomes (23)

• Change in eGFR

  12 Months, 24 Months and through study completion (an average of 4.5 years)

• Change in annualized eGFR slope

  12 Months, 24 Months and through study completion (an average of 4.5 years)

• Change in urine albumin levels

  12 Months, 24 Months and through study completion (an average of 4.5 years)

Study Arms (1)

PRX-102 1 mg/kg every 2 weeks or PRX-102 2 mg/kg every 4 weeks

EXPERIMENTAL

PRX-102 1 mg/kg every 2 weeks or PRX-102 2 mg/kg every 4 weeks (available only in the optional extension part)

Drug: PRX-102 1 mg/kg every 2 weeks; Drug: PRX-102 2 mg/kg every 4 weeks

Interventions

PRX-102 1 mg/kg every 2 weeks DRUG

PRX-102 1 mg/kg every 2 weeks

Also known as: pegunigalsidase alfa, Recombinant human alpha galactosidase-A

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 DRUG

PRX-102 2 mg/kg every 4 weeks

Also known as: pegunigalsidase alfa, Recombinant human alpha galactosidase-A

PRX-102 1 mg/kg every 2 weeks or PRX-102 2 mg/kg every 4 weeks

Eligibility Criteria

• Age: 13 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have been born in Japan and have their biological parents and all 4 grandparents of Japanese descent
• A documented diagnosis of Fabry disease, as determined by the following:
• Males: Plasma and/or leukocyte alpha-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
• Estimated glomerular filtration rate (eGFR) at screening ≥40 mL/min/1.73 m2. For adults, this will be calculated using the Japanese Modified Chronic Kidney Disease Epidemiology Collaboration (JPN-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.
• Clinical condition that in the opinion of the Investigator requires treatment with ERT
• A female subject (including an adolescent in Cohort C, if applicable) must meet one of the following criteria:
• If of childbearing potential, she must:
• Have a negative serum pregnancy test result at screening, AND
• Agree to undergo a urine pregnancy test at baseline and every 12 weeks thereafter up to the final treatment, AND
• 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 system (IUS)
• Combined (both oestrogen and progestogen) hormonal contraception (oral) associated with inhibition of ovulation, supplemented with a barrier method (preferably male condom)
• Bilateral tubal occlusion

You may not qualify if:

• 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 9 to 24 months before screening, indicating absence of renal impairment. eGFR to be calculated using the JPN-CKD-EPI creatinine equation (2009).
• 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); or 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 infusion received
• 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

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead
• ICON plc: collaborator

Study Sites (10)

Fukuoka University Chikushi Hospital

Chikushino-shi, Fukuoka, 818-8502, Japan

WITHDRAWN

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

RECRUITING

University of the Ryukyu Hospital

Nishihara, Okinawa, 903-0125, Japan

RECRUITING

Osaka University Hospital

Suita, Osaka, 565-0871, Japan

RECRUITING

Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-ku, Tokyo

Bunkyo-ku, Tokyo, 113-0033, Japan

RECRUITING

Tokyo Jikei University Hospital

Minato-ku, Tokyo, 105-8461, Japan

RECRUITING

Keio University Hospital

Shinjuku-ku, Tokyo, 160-8582, Japan

RECRUITING

Asahikawa Medical University Hospital

Asahikawa, Japan

RECRUITING

Niigata University Medical & Dental Hospital

Niigata, 951-8520, Japan

RECRUITING

National Hospital Organization Okayama Medical Center

Okayama, Japan

NOT YET RECRUITING

MeSH Terms

Conditions

Fabry Disease

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Central Study Contacts

Chiesi Clinical Trial

CONTACT

+3905212791; clinicaltrials_info@chiesi.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2022
• First Posted: February 2, 2023
• Study Start: August 1, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): August 1, 2029
• Last Updated: March 18, 2026

Record last verified: 2026-03

Locations

JP (10)