Clinical trial

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

ID

Name

CLI-06657AA1-01

Description

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

Trial arms

Trial start

2024-10-01

Estimated PCD

2027-12-01

Trial end

2028-03-01

Status

Not yet recruiting

Phase

Early phase I

Treatment

PRX-102 1 mg/kg every two weeks

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

Arms:

Single Arm - Pegunigalsidase alfa (PRX-102)

Other names:

pegunigalsidase alfa, Recombinant human alpha galactosidase-A

Size

22

Primary endpoint

Incidence of Treatment Emergent Adverse Events (TEAEs)

12 Months

Incidence of Infusion Related Reactions (IRRs)

12 Months

Incidence of Injection site reactions (ISRs)

12 Months

Change in Tanner stage

Baseline and 12 Months

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

Baseline and 12 Months

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

Baseline and 12 Months

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

Baseline and 12 Months

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

Baseline and 12 Months

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

Baseline and 12 Months

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

Baseline and 12 Months

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

Baseline and 12 Months

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

Baseline and 12 Months

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]

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]

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]

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

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)

Baseline, week 2, week 4, week 12, week 26 and week 52]

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

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)

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)

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)

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

Baseline and 12 Months

Change in annualized eGFR slope

Baseline and 12 Months

Change in urine albumin levels

Baseline and 12 Months

Change in urine protein levels

Baseline and 12 Months

Change from baseline in LVMi as assessed by echocardiogram

Baseline and 12 Months

Change from baseline in LVMi as assessed by echocardiogram

Baseline and 12 Months

Change from baseline in LVMi as assessed by echocardiogram

Baseline and 12 Months

Change from baseline in LVMi as assessed by echocardiogram

Baseline and 12 Months

Change from baseline in LVMi as assessed by echocardiogram

Baseline and 12 Months

Incidence of any cardiac arrythmias as assessed by Holter ECG

Baseline and 12 Months

Change in plasma levels of cardiac biomarkers

Baseline and 12 Months

Change in plasma level of Gb3 concentration (nM)

Baseline and 12 Months

Change in plasma level of lyso-Gb3 (nM)

Baseline and 12 Months

Change in urine level of lyso-Gb3 (nM)

Baseline and 12 Months

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

Baseline and 12 Months

Incidence of Fabry Clinical Events

12 Months

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

Baseline and 12 Months

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

Baseline and 12 Months

Change from baseline of FPHPQ scores

Baseline and 12 Months

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

Baseline and 12 Months

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

Baseline and 12 Months

Eligibility criteria

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.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2', 'PHASE3'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 22, 'type': 'ESTIMATED'}}

Updated at

2024-03-25

1 organization

1 product

1 indication

Product

Indication

Organization

Chiesi Farmaceutici