Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Exploratory Efficacy Parameters of PRX-102 Administered by Intravenous Infusion to Adult Fabry Patients

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2012-004786-40-ES
• Date of registration: 05/09/2013
• Prospective Registration: Yes
• Primary sponsor: Protalix Ltd.
• Public title: Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Exploratory Efficacy Parameters of PRX-102 Administered by Intravenous Infusion to Adult Fabry Patients
• Scientific title: A Phase 1/2, Open Label, Dose Ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Exploratory Efficacy Parameters of PRX-102 Administered by Intravenous Infusion Every 2 Weeks for 12 Weeks to Adult Fabry Patients
• Date of first enrolment: 13/11/2013
• Target sample size: 18
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004786-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Argentina, Australia, Israel, Paraguay, Serbia, Spain, United Kingdom, United States

Contacts

• Name: Rainer Schuckelt
• Affiliation: Cato Europe GmbH

• Name: Rainer Schuckelt
• Affiliation: Cato Europe GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1.Symptomatic adult Fabry patients (> or = to 18 yrs, males and females)
2.Males: plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than lower limit of normal (LLN in plasma=3.2 nmol/hr/ml, LLN in leucocytes=32 nmol/hr/mg/protein)
3.Females: historical genetic test results consistent with Fabry mutations
4.Globotriaosylceramide (Gb3) concentration in urine > 1.5 times upper normal limit
5.Patients who have never received enzyme replacement therapy (ERT) in the past, or patients who have not received ERT in the past 6 months and have a negative anti PRX-102 antibody test
6.Chronic kidney disease - stages 1 or 2 (CKD1 or 2) (Appendix 7) with proteinuria > 200 mg/g protein-to-creatinine ratio measured in a Spot urine sample or equivalent demonstrated in at least one of 2 separate samples (one sample in screening visit and the other from historical data)
7.The patient signs informed consent
8.Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically acceptable method of contraception, not including the rhythm method
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 17
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
1.Participation in any trial of an investigational drug within 30 days prior to study screening
2.Chronic kidney disease stages 3-5 (CKD 3-5) (Appendix 7)
3.History of dialysis or renal transplantation
4.Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
5.Severe myocardial fibrosis by MRI (> or = to 2 late-enhancement [LE] positive left ventricular segments) (Weidemann et al. 2009)
6.History of clinical stroke
7.Pregnant or nursing
8.Presence of HIV and/or HBsAg and/or Hepatitis C infections
9.Known allergies to ERT
10.Known allergy to Gadolinium based contrast agents
11.Presence of any medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator and/or Medical Director, would interfere with the patients compliance with the requirements of the study


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Fabry disease
MedDRA version: 16.1 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Name: PRX102
Product Code: PRX102
Pharmaceutical Form: Infusion
INN or Proposed INN: PRX102
CAS Number: 1333358-30-7
Current Sponsor code: PRX102
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Product Name: PRX102
Product Code: PRX102
Pharmaceutical Form: Infusion
INN or Proposed INN: PRX102
CAS Number: 1333358-30-7
Current Sponsor code: PRX102
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Product Name: PRX102
Product Code: PRX102
Pharmaceutical Form: Infusion
INN or Proposed INN: PRX102
CAS Number: 1333358-30-7
Current Sponsor code: PRX102
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Samples will be taken at first and last infusions at the following time points: pre-infusion (baseline); 1 hour after the beginning of the infusion; at the end of the infusion; 1, 4, 8, 24, 48±3, 72±3, 96±3 hours and 2 weeks ± 3 days post-infusion

Main Objective: To evaluate the safety, tolerability, pharmacokinetics and exploratory efficacy parameters of PRX-102 in adult Fabry patients.

Primary end point(s): The following PK parameters will be derived from the plasma concentration versus time profiles to determine the profile of the study drug: Cmax, t1/2, Tmax, AUC0-t, and AUC0-8.

Secondary Objective: -Gb3 concentrations assessed by Gb3 concentrations in plasma and urine sediment. (Gb3 is a component in the cell membrane and its accumulation in body tissues results in Fabry Disease).
-Globotriaosylsphingosine(LysoGb3) concentrations assessed by LysoGb3
concentrations in plasma
-Kidney function measurement of glomerular filtration and proteinuria
-Pain assessed by a short term brief pain inventory
-Assessment of gastrointestinal symptoms

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 12 weeks

Secondary end point(s): Efficacy Variables:
-Gb3 concentrations in plasma and urine sediment at baseline and at every infusion during the study
-Globotriaosylsphingosine (Lyso-Gb3) concentration in plasma at baseline and at every infusion during the study
-Assessment of gastrointestinal symptoms at baseline and at last infusion (Appendix 8)
-Kidney functions (eGFR and proteinuria) at baseline and at last infusion
-Short Form Brief Pain Inventory (BPI) at baseline and at last infusion (Appendix 9)
The following additional procedures will be performed only at baseline in this protocol as a reference point for evaluation as an exploratory efficacy endpoint parameter in an extension protocol. These parameters are not expected to show significant response during the 12 weeks of dosing in this study and will not be repeated at the last infusion.
-Kidney biopsy for Gb3 concentration (Appendix 5)
-Skin punch biopsy for Gb3 concentration (Appendix 5)
-MRI of the heart and brain
-Mainz Severity Score Index (MSSI) (Appendix 6)
-Cardiac function assessment (echocardiography and stress test)

Safety Variables
-Safety will be assessed by the frequency, severity, and duration of treatment-emergent AEs (adverse events), including clinically significant laboratory abnormalities, ECG changes from baseline, physical examination findings and assessment of the injection site after administration of the study drug
-Anti-PRX-102 antibodies will be assessed before dosing at: baseline, every month, at last infusion, and 1 and 3 months after last infusion

Secondary ID(s)

2012-004786-40-GB

PB-102-F01

Source(s) of Monetary Support

Protalix Ltd.