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

Fabry Disease Clinical Trial

— FLY  

Official title:

Multi-centre, Open-label Trial to Assess the saFety, Pharmacodynamics, Efficacy and Pharmacokinetics of pegunigaLsidase Alfa in Patients From 2 Years to Less Than 18 Years of Age With Confirmed FabrY Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06328608
• Other study ID #: CLI-06657AA1-01
• Secondary ID: 2022-503128-29
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: October 2024
• Est. completion date: March 2028

Study information

• Verified date: March 2024
• Source: Chiesi Farmaceutici S.p.A.
• Contact: Chiesi Clinical Trial
• Phone: +3905212791
• Email: clinicaltrials_info[@]chiesi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 22
• Est. completion date: March 2028
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fabry Disease

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Chiesi Farmaceutici S.p.A.	ICON plc

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment Emergent Adverse Events (TEAEs)		12 Months
Primary	Incidence of Infusion Related Reactions (IRRs)		12 Months
Primary	Incidence of Injection site reactions (ISRs)		12 Months
Primary	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.	Baseline and 12 Months
Primary	Change from baseline of 12-lead ECG quantitative parameters: Mean Heart Rate		Baseline and 12 Months
Primary	Change from baseline of 12-lead ECG quantitative parameters: PR Interval		Baseline and 12 Months
Primary	Change from baseline of 12-lead ECG quantitative parameters: QRS Duration		Baseline and 12 Months
Primary	Change from baseline of 12-lead ECG quantitative parameters: QT Interval		Baseline and 12 Months
Primary	Change from baseline of 12-lead ECG quantitative parameters: QTc Interval		Baseline and 12 Months
Primary	Change from baseline of 12-lead ECG quantitative parameters: ST Segment		Baseline and 12 Months
Primary	Incidence of treatment-emergent Anti-Drug Antibodies (ADAs)		Baseline and 12 Months
Primary	Incidence of premedication use at each visit and change of infusion premedications from baseline		Baseline and 12 Months
Primary	Pharmacokinetics: Time to maximum plasma concentration (tmax)		Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Primary	Pharmacokinetic : Area under the plasma concentration-time curve from time 0 to time t (AUC0 t)		Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Primary	Pharmacokinetics: Area under the curve from time 0 to 2 weeks (AUC0-2wk)		Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Primary	Pharmacokinetics: Area under the curve from time 0 to infinity (AUC0-8)		Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Primary	Pharmacokinetics: Terminal half-life (t1/2)		Baseline, week 2, week 4, week 12, week 26 and week 52]
Primary	Pharmacokinetics: Area under the curve over a dosing interval (AUCt)		Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Primary	Pharmacokinetics: Observed drug concentration at the end of the dosing interval (Ct)		Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Primary	Pharmacokinetics: Clearance (Cl)		Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Primary	Pharmacokinetics: Volume of distribution (Vz)		Stage I - Baseline, week 2, week 4, week 12, week 26 and week 52; Stage II -Baseline, week 12, week 26 and week 52]
Primary	Change in eGFR		Baseline and 12 Months
Primary	Change in annualized eGFR slope		Baseline and 12 Months
Primary	Change in urine albumin levels		Baseline and 12 Months
Primary	Change in urine protein levels		Baseline and 12 Months
Primary	Change from baseline in LVMi as assessed by echocardiogram	Echocardiogram parameters include left ventricular mass index (LVMi)	Baseline and 12 Months
Primary	Change from baseline in LVMi as assessed by echocardiogram	Echocardiogram parameters include ejection fraction	Baseline and 12 Months
Primary	Change from baseline in LVMi as assessed by echocardiogram	Echocardiogram parameters include, fractional shortening	Baseline and 12 Months
Primary	Change from baseline in LVMi as assessed by echocardiogram	Echocardiogram parameters include left ventricular mass	Baseline and 12 Months
Primary	Change from baseline in LVMi as assessed by echocardiogram	Echocardiogram parameters include valve abnormalities and thickness.	Baseline and 12 Months
Primary	Incidence of any cardiac arrythmias as assessed by Holter ECG		Baseline and 12 Months
Primary	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.	Baseline and 12 Months
Primary	Change in plasma level of Gb3 concentration (nM)		Baseline and 12 Months
Primary	Change in plasma level of lyso-Gb3 (nM)		Baseline and 12 Months
Primary	Change in urine level of lyso-Gb3 (nM)		Baseline and 12 Months
Primary	Incidence of change from baseline in the number of different pain medications		Baseline and 12 Months
Primary	Incidence of Fabry Clinical Events	FCEs are classified into four categories: renal, cardiac, cerebrovascular and death due to non-cardiac reasons	12 Months
Primary	Change from baseline of Mainz Severity Score Index (MSSI) scores	Domains (general, neurological, cardiovascular, renal dysfunction)	Baseline and 12 Months
Primary	Change from baseline of PedsQL-GI (or GSRS for subjects who reaches 18 yrs of age) scores		Baseline and 12 Months
Primary	Change from baseline of FPHPQ scores		Baseline and 12 Months
Primary	Change from baseline of PedsQL-PPQ (or BPI-SF for subjects who reaches 18 yrs of age) scores		Baseline and 12 Months
Primary	Change from baseline of EQ-5D-Y (or EQ-5D-5L for subjects who reaches 18 yrs of age) scores		Baseline and 12 Months