An Extension of the PB102F01 study: A clinical study in patients with Fabry disease to assess the safety, tolerability, and the body processing of the medication PRX102, which will be given as an infusion.

• Register: EUCTR
• Last refreshed on: 10 October 2016
• Main ID: EUCTR2013-002554-78-ES
• Date of registration: 20/09/2013
• Prospective Registration: Yes
• Primary sponsor: Protalix Ltd.
• Public title: An Extension of the PB102F01 study: A clinical study in patients with Fabry disease to assess the safety, tolerability, and the body processing of the medication PRX102, which will be given as an infusion.
• Scientific title: An Extension of 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 38 Weeks (9 Months) to Adult Fabry Patients
• Date of first enrolment: 26/11/2013
• Target sample size: 18
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002554-78
• 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:
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

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.Completion of Phase 1/2 study PB-102-F01
2.The patient signs informed consent
3.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. Acceptable methods of contraception include hormonal products, intrauterine device, or male or female condoms. Contraception should be used for 1 month after termination of treatment.
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.Pregnant or nursing
2.Presence of any medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator and/or Medical Director, would interfere with the patient?s 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: 14.1 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: Clinical lab tests, Physical Examination, ECG will be assessed at Screening, Visit 7 (total treatment of ~ 6 months), 13 and 20 (total treatment of ~12 months). Adverse events will be assessed at every visit.
Injection site reactions will be assessed at every visit up to visit 20.
Anti-PRX-102 antibodies will be assessed at Screening, Visit 2, 7, 11, 15, 20 and 2 months after visit 20.

Primary end point(s): The main outcome will be evaluation of safety in PRX102 treated subjects at each dose. Safety will be assessed by the frequency, severity, and duration of treatment-emergent adverse events (TEAEs), including clinically significant laboratory abnormalities, ECG changes from baseline, physical examination findings and assessment of the injection
site reactions after administration of the study drug. Also AntiPRX102
antibodies will be assessed.

Secondary Objective: All exploratory endpoints that were evaluated during the Phase 1/2 study PB-102-F01 will continue to be assessed in the extension protocol .These include:
-Gb3 concentration in kidney and in skin (assessed histologically in kidney biopsy and skin punch biopsy )
-Gb3 concentrations in plasma and urine sediment
-LysoGb3 concentration in plasma
-Assessment of gastrointestinal symptoms
-Kidney functions (eGFR and proteinuria)
-Short Form Brief Pain Inventory (BPI)
-Left ventricular mass (LVM) and myocardial fibrosis assessment by cardiac MRI
-Cardiac function assessment by echocardiography and stress test
-Cerebrovascular disease assessment (clinical and MRI evaluation)
-Mainz Severity Score Index (MSSI)

Main Objective: To evaluate the ongoing safety, tolerability, pharmacokinetics and exploratory efficacy parameters of PRX102 in adult Fabry patients who have successfully completed treatment with PRX102 in the core study PB-102-F01, and are continuing to receive treatment at the dose assigned to each patient in the PB-102-F01 study. This extension study may provide important additional long term information on safety, tolerability and clinical outcome in patients treated with different doses of PRX102.

Secondary Outcome(s)

Secondary end point(s): PHARMACOKINETIC ENDPOINTS:
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, AUC0t, and AUC0?.
EXPLORATORY EFFICACY ENDPOINTS:
-Globotriaosylceramide (Gb3) concentration in kidney (assessed histologically in kidney biopsy)
-Gb3 concentration in skin (assessed histologically in skin punch biopsy)
-Gb3 concentrations in plasma and urine sediment
-Globotriaosylsphingosine (LysoGb3) concentration in plasma
-Assessment of gastrointestinal symptoms
-Kidney functions (eGFR and proteinuria)
-Short Form Brief Pain Inventory (BPI)
-Left ventricular mass (LVM) and myocardial fibrosis assessment by cardiac MRI
-Cardiac function assessment (echocardiography and stress test)
-Cerebrovascular disease assessment (clinical and MRI evaluation)
-Mainz Severity Score Index (MSSI)

Timepoint(s) of evaluation of this end point: EXPLORATORY:
Visit 7: Kidney biopsy & skin punch biopsy
Screening, visit 7, 13 & 20 (after total treatment of 12 months): Gb3 concentrations in plasma and urine sediment, Globotriaosylsphingosine (LysoGb3) concentration, Assessment of gastrointestinal symptoms, Kidney functions,Short Form Brief Pain Inventory
Visit 7 & 20: Left ventricular mass (LVM) and myocardial fibrosis, Cardiac function Mainz Severity Score Index
Visit 20: Cerebrovascular disease assessment
PK: preinfusion, 1 hour after infusion starts, end of infusion, 1,4,8,24,48,72,96 hours post infusions and 2 weeks post infusión.

Secondary ID(s)

2013-002554-78-GB

NCT01769001

PB-102-F02

Source(s) of Monetary Support

Protalix Ltd.