E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Fabry disease is an inherited condition caused by a deficiency of an enzyme, leading to a range of systemic symptoms (potentially life-threatening), such as kidney failure, heart attacks and strokes. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016016 |
E.1.2 | Term | Fabry's disease |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The principal research objective of this study is to evaluate the safety, tolerability, pharmacokinetics (the amount of exposure to the drug amd turnover time in the blood) and exploratory efficacy parameters of PRX-102, a chemically modified enzyme (alpha galactosidase) expressed in plant cells and indicated for long-term enzyme replacement therapy in adult patients with diagnosed Fabry disease (alpha galactosidase deficiency). |
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E.2.2 | Secondary objectives of the trial |
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).
Kidney function measurement of glomerular filtration and proteinuria
Pain assessed by a short term brief pain inventory
Assessment of gastrointestinal symptoms |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Symptomatic adult Fabry patients (≥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 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 |
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E.4 | Principal 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 (≥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 patient’s compliance with the requirements of the study |
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E.5 End points |
E.5.1 | 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-∞. |
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E.5.1.1 | 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, 72 , 96 hours and 2 weeks post-infusion |
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E.5.2 | Secondary end point(s) |
EXPLORATORY EFFICACY ENDPOINTS: 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 Kidney functions (eGFR and proteinuria) at baseline and at last infusion Short Form Brief Pain Inventory (BPI) at baseline and at last infusion 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 (Appendix 5) MRI of the heart and brain Mainz Severity Score Index (MSSI) (Whybra et al. 2004) Cardiac function assessment (echocardiography and stress test)
SAFETY ENDPOINTS: Changes from baseline in: Clinical laboratory tests Physical examination Assessment of the injection site ECG Treatment-emergent adverse events Anti-PRX-102 antibodies |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Chile |
Israel |
Paraguay |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |