A Study to Learn About the Safety and Effects of the Study Drug PRX-102 in Children and Adolescents With Fabry Disease

Phase 3RecruitingNCT06328608

Chiesi Farmaceutici S.p.A.22 enrolled

Overview

A Study to Learn About the Safety and Effects of the Study Drug PRX-102 in Children and Adolescents with Fabry Disease.

This study aims to learn how safe pegunigalsidase alfa (PRX-102 for short) is and how it works at treating Fabry disease in children and adolescents. PRX-102 is an enzyme replacement therapy (ERT), meaning it acts like a natural enzyme. PRX-102 is given through a needle placed in a vein (intravenous infusion) every two weeks. The main questions this study aims to answer are: * Which is the safest and most effective dose to be given to children and adolescents. * Which effects PRX-102 has on signs and symptoms of Fabry disease (e.g. renal and cardiac function, pain, gastrointestinal symptoms) 20 to 22 boys and girls with Fabry disease between the ages of 2 and 17 will be part of this study. There will be three age cohorts, with children aged 2 to 7 years included (enrolled) in Cohort A, children aged 8 to 12 years in Cohort B, and adolescents aged 13 to less than 18 years in Cohort C. The study is divided into three parts, or "stages": * A dose-finding stage (Stage I). In this stage, researchers will determine the dose for children. * A confirmatory stage (Stage II). In this part, researchers will learn about the safety and efficacy of PRX-102. * and an optional extension stage (Stage III) will continue until the study drug becomes commercially available or the Sponsor chooses to end this study. PRX-102 will be given at the study visits, which will occur at least every two weeks. Tests for verifying the study drug's safety and efficacy and determining the dose will also be conducted at different time points throughout the study (not all tests will be done at all visits). These tests may include a review of any health problems and medications the participants have had or taken since the last visit; a physical examination; ECG; ultrasound of the heart; questionnaires that evaluate the nature and severity of Fabry disease symptoms, quality of life and pain; a collection of blood and urine samples for standard safety tests, to analyse the severity of Fabry disease and to see how the drug is behaving and how long it remains active in the body (this involves taking multiple blood samples over several days with the first sample taken just before the start of the PRX-102 infusion and the last one taken just before the start of the next PRX-102 at the next visit).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Fabry Disease

Interventions

PRX-102 1 mg/kg every two weeksDRUG

Drug: PRX-102 1 mg/kg every two weeks

Eligibility

Sex: ALLMin age: 2 YearsMax age: 17 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participants with the provision of informed consent from their legal guardians * Boys and girls aged 2 to 7 years (Cohort A), 8 to 12 years (Cohort B), or 13 to \<18 years (Cohort C). * Confirmed diagnosis of Fabry disease * Presence of at least one of the following characteristic features of Fabry disease: neuropathic pain, cornea verticillata, and/or clustered angiokeratoma. * History of Fabry pain: Fabry crises OR chronic pain. * Clinical condition that, in the investigator's opinion, requires ERT treatment. Exclusion Criteria: All Subjects: * Estimated glomerular filtration rate (eGFR) at screening \< 80 mL/min/1.73 m2. * History of type I hypersensitivity reactions (anaphylactic or anaphylactoid life-threatening reaction) to other ERT treatment for Fabry disease or any component of the study drug. * Initiation of treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) or a dose change in ongoing treatment in the four weeks before screening. * 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. * Currently taking another investigational drug for any condition. * History of acute kidney injury in the 12 months before screening, including specific kidney diseases (e.g., acute interstitial nephritis, acute glomerular and vasculitic renal diseases); non-specific conditions (e.g., ischaemia, toxic injury); or extrarenal pathology (e.g., prerenal azotaemia, acute postrenal obstructive nephropathy). * History of renal dialysis or kidney transplantation. * History of or current malignancy requiring treatment. * Severe cardiomyopathy or significant unstable cardiac disease within six months before screening. * A positive test for Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) within three months before screening. * Presence of any medical, emotional, behavioural, or psychological condition that, in the Investigator's judgement, could interfere with the subject's compliance with the requirements of the study. Additional Exclusion Criteria for Subjects Enrolled in Stage I: * Female * Non-classic form of Fabry disease * Receipt of treatment for Fabry disease within six months before screening * Positive for anti-PRX-102 antibodies at screening Additional Exclusion Criteria for Subjects in Stage II (i.e., non-treatment naïve males or females): * Unwilling to discontinue current ERT treatment for Fabry disease before baseline. * 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.

Locations (12)

Phoenix Children's

Phoenix, Arizona, United States

RECRUITING

Emory Genetics Clinical Trials Center

Atlanta, Georgia, United States

Outcomes

Primary Outcomes

Incidence of Treatment Emergent Adverse Events (TEAEs)

Time frame: 12 Months

Incidence of Infusion Related Reactions (IRRs)

Time frame: 12 Months

Incidence of Injection site reactions (ISRs)

Time frame: 12 Months

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.

Time frame: Baseline and 12 Months

Change from baseline of 12-lead ECG quantitative parameters: Mean Heart Rate

Time frame: Baseline and 12 Months

Change from baseline of 12-lead ECG quantitative parameters: PR Interval

Time frame: Baseline and 12 Months

Change from baseline of 12-lead ECG quantitative parameters: QRS Duration

Time frame: Baseline and 12 Months

Change from baseline of 12-lead ECG quantitative parameters: QT Interval

Time frame: Baseline and 12 Months

Change from baseline of 12-lead ECG quantitative parameters: QTc Interval

Time frame: Baseline and 12 Months

Change from baseline of 12-lead ECG quantitative parameters: ST Segment

Time frame: Baseline and 12 Months

Incidence of treatment-emergent Anti-Drug Antibodies (ADAs)

Central Contacts

Chiesi Clinical Trial

CONTACT

+3905212791 clinicaltrials_info@chiesi.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

University of Iowa

Iowa City, Iowa, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

NOT_YET_RECRUITING

University of Utah

Salt Lake City, Utah, United States

RECRUITING

Lysosomal and Rare Disorders Research and Treatment Center Inc

Fairfax, Virginia, United States

NOT_YET_RECRUITING

UK für Kinder- und Jugendheilkunde der PMU Salzburg

Salzburg, Austria

RECRUITING

Centre Hospitalier Universitaire (CHU) de Bordeaux - Groupe Hospitalier Pellegrin

Bordeaux, France

RECRUITING

Hopital Arnaud de Villeneuve

Montpellier, France

RECRUITING

Haukeland Universitetssjukehus

Bergen, Norway

RECRUITING

...and 2 more locations

Time frame: Baseline and 12 Months

Incidence of premedication use at each visit and change of infusion premedications from baseline

Time frame: Baseline and 12 Months

Pharmacokinetics: Time to maximum plasma concentration (tmax)

Time frame: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

Pharmacokinetic : Area under the plasma concentration-time curve from time 0 to time t (AUC0 t)

Time frame: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

Pharmacokinetics: Area under the curve from time 0 to 2 weeks (AUC0-2wk)

Time frame: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

Pharmacokinetics: Area under the curve from time 0 to infinity (AUC0-∞)

Time frame: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

Pharmacokinetics: Terminal half-life (t1/2)

Time frame: Baseline, week 2, week 4, week 12, week 26 and week 52]

Pharmacokinetics: Area under the curve over a dosing interval (AUCτ)

Time frame: Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

Pharmacokinetics: Observed drug concentration at the end of the dosing interval (Cτ)

Time frame: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

Pharmacokinetics: Clearance (Cl)

Time frame: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

Pharmacokinetics: Volume of distribution (Vz)

Time frame: Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]

Change in eGFR

Time frame: Baseline and 12 Months

Change in annualized eGFR slope

Time frame: Baseline and 12 Months

Change in urine albumin levels

Time frame: Baseline and 12 Months

Change in urine protein levels

Time frame: Baseline and 12 Months

Change from baseline in LVMi as assessed by echocardiogram

Echocardiogram parameters include left ventricular mass index (LVMi)

Time frame: Baseline and 12 Months

Change from baseline in LVMi as assessed by echocardiogram

Echocardiogram parameters include ejection fraction

Time frame: Baseline and 12 Months

Change from baseline in LVMi as assessed by echocardiogram

Echocardiogram parameters include, fractional shortening

Time frame: Baseline and 12 Months

Change from baseline in LVMi as assessed by echocardiogram

Echocardiogram parameters include left ventricular mass

Time frame: Baseline and 12 Months

Change from baseline in LVMi as assessed by echocardiogram

Echocardiogram parameters include valve abnormalities and thickness.

Time frame: Baseline and 12 Months

Incidence of any cardiac arrythmias as assessed by Holter ECG

Time frame: Baseline and 12 Months

Change in plasma levels of cardiac biomarkers

High-sensitivity cardiac troponin T (hs-cTnT) and N- terminal pro brain natriuretic peptide (NT-Pro BNP) will be assessed.

Time frame: Baseline and 12 Months

Change in plasma level of Gb3 concentration (nM)

Time frame: Baseline and 12 Months

Change in plasma level of lyso-Gb3 (nM)

Time frame: Baseline and 12 Months

Change in urine level of lyso-Gb3 (nM)

Time frame: Baseline and 12 Months

Incidence of change from baseline in the number of different pain medications

Time frame: Baseline and 12 Months

Incidence of Fabry Clinical Events

FCEs are classified into four categories: renal, cardiac, cerebrovascular and death due to non-cardiac reasons

Time frame: 12 Months

Change from baseline of Mainz Severity Score Index (MSSI) scores

Domains (general, neurological, cardiovascular, renal dysfunction)

Time frame: Baseline and 12 Months

Change from baseline of PedsQL-GI (or GSRS for subjects who reaches 18 yrs of age) scores

Time frame: Baseline and 12 Months

Change from baseline of FPHPQ scores

Time frame: Baseline and 12 Months

Change from baseline of PedsQL-PPQ (or BPI-SF for subjects who reaches 18 yrs of age) scores

Time frame: Baseline and 12 Months

Change from baseline of EQ-5D-Y (or EQ-5D-5L for subjects who reaches 18 yrs of age) scores

Time frame: Baseline and 12 Months