A study to assess the renal function in young male patients with Fabry disease who have never received any specific treatment for this disease.

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2012-001966-14-ES
• Date of registration: 03/09/2012
• Prospective Registration: Yes
• Primary sponsor: Genzyme, a Sanofi Company
• Public title: A study to assess the renal function in young male patients with Fabry disease who have never received any specific treatment for this disease.
• Scientific title: A Cross-sectional Study of Renal Function in Treatment-naïve, Young Male Patients with Fabry Disease - FABRY-MAP
• Date of first enrolment: 25/10/2012
• Target sample size: 45
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001966-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Netherlands, Norway, Spain, United Kingdom, United States

Contacts

• Name: Medical Information Genzyme Europe
• Affiliation: Genzyme Europe BV

• Name: Medical Information Genzyme Europe
• Affiliation: Genzyme Europe BV

Key inclusion & exclusion criteria

Inclusion criteria:
A patient must meet all of the following criteria to be eligible for this study.
1. The patient and/or their parent/legal guardian is willing and able to provide signed informed consent. If the patient is below the age of consent per local guidelines, he is willing to provide assent, if
deemed able to do so.
2. The patient must have a confirmed diagnosis of Fabry disease as documented by leukocyte ?-galactosidase A (?GAL) of <4 mol/hr/mg leukocyte (preferred assay; results from a central
laboratory). If the leukocyte ?GAL activity assay is difficult to obtain, the patient may be enrolled based on documented plasma ?GAL <1.5 nmol/hr/mL (results from a central laboratory), with the
agreement of the Genzyme Medical Monitor.
3. The patient must be male and ?5 and ?25 years of age at screening.
Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
A patient who meets any of the following criteria will be excluded from this study.
1. Patient has received prior treatment with enzyme replacement therapy (ERT) or oral pharmacological chaperone therapy for Fabry disease.
2. Patient has received an investigational drug within 30 days of the screening visit.
3. Patient is receiving any of the following medications and is clinically unable or unwilling to temporarily discontinue treatment with these medications for the indicated washout period prior to
the renal function assessments until completion of these assessments:
? Angiotensin converting enzyme inhibitors or angiotensin receptor blockers (6 week washout);
? Non-steroidal anti-inflammatory drugs (3 day washout).
NOTE: Patients who are on chronic dialysis or have had a kidney transplant will not be required to discontinue the above medications because renal function assessments will not be performed in these
patients.
4. Patient has any contraindication mentioned in the labeling of iohexol. NOTE: patients with an eGFR <30 mL/min/1.73m2 and patients who are on chronic dialysis or have had a kidney transplant may be enrolled irrespective of any contraindication to iohexol because iGFR will not be measured in these patients.
5. Patient has any medical condition or extenuating circumstance which, in the opinion of the Investigator, could interfere with the patient?s ability to complete all study procedures, or with the
interpretation of study results (e.g., diabetes mellitus).
6. The patient and/or their parent or legal guardian, in the opinion of the Investigator, is unable to adhere to the requirements of the study.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Fabry disease
MedDRA version: 15.0 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Trade Name: Iohexol
Product Name: OMNIPAQUE
Product Code: Not applicable
Pharmaceutical Form: Solution for injection
INN or Proposed INN: iohexol
Current Sponsor code: Not applicable
Other descriptive name: iohexol
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 300-

Primary Outcome(s)

Secondary Objective: To provide a reference group for comparison with interventional clinical trials of Fabry disease.

Timepoint(s) of evaluation of this end point: ? eGFR: screening, clinical investigation visit (after washout)
? iGFR:clinical investigation visit (after washout)
? ACR, PCR, RBP and ?2-microglobulin, as measured in three first morning void urine samples, each obtained at least 1 week apart and not more than 2 weeks apart.
? ECG: clinical investigation visit
? Electrocardiography: clinical investigation visit
? Information on GI symptoms: screening
? PedsQL, PPQ: screening
? BPI[SF]: screening
? Blood and urine exploratory biomarkers: clinical investigation visit (after washout)
? Plasma and urine globotriaosylceramide (total GL-3 and lyso-GL-3):clinical investigation visit
? Genotyping for ?GAL gene mutations: clinical investigation visit

Main Objective: To document renal function and other Fabry disease manifestations across age in treatment-naïve, young male patients with Fabry disease.

Primary end point(s): Renal Function (all assessments by central laboratories):
? GFR estimated from serum creatinine using age-appropriate formulas (eGFR).
? GFR measurement by plasma iohexol clearance (iGFR). NOTE: iGFR will not be measured for patients with a screening eGFR <30 mL/min/1.73m2.
? Albumin/creatinine ratio (ACR), total protein/creatinine ratio (PCR), retinol binding protein (RBP), and ?2-microglobulin, as measured in three first morning void urine samples, each obtained at least 1 week apart and not more than 2 weeks apart.

Cardiovascular Function (all tests read by central laboratories)
? Standard 12-lead electrocardiogram (ECG) parameters and abnormalities.
? Standard cardiac dimensions, calculated ejection fraction (EF), and valve abnormalities by 2-dimensional Doppler echocardiograph and mitral annulus velocities by optional tissue Doppler imaging (based on the site?s technical capabilities).

Gastrointestinal (GI) Symptoms
? Information on GI symptoms, obtained by asking patients a series of specific questions.

Quality of Life (QoL):
? Pediatric QoL (PedsQL) Pediatric Pain Questionnaire (PPQ) in patients 5 to 17 years of age at screening.
? Brief Pain Inventory (Short Form) (BPI[SF]) in patients ?18 years of age at screening.

Exploratory Biomarkers (all assessments by central laboratories):
? Blood and urine samples will also be collected for exploratory analyses of potential biomarkers of Fabry disease, which will be identified on the basis of emerging scientific data and will be analyzed individually or in multi-analyte biomarker panels. Blood and urine samples collected for exploratory biomarker analyses in this study will not be used for genetic testing.

Other Disease Characteristics (all assessments by central laboratories)
? Plasma and urine globotriaosylceramide (total GL-3 and lyso-GL-3).
? Genotyping for ?GAL gene mutations.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Continuous monitoring throughout the study from written informed consent through the follow-up phone contact.

Secondary end point(s): Safety will be assessed by evaluation of the incidence of adverse events (AEs), especially those events at least possibly related to iohexol or to other study procedures.

Secondary ID(s)

AGAL19110

Source(s) of Monetary Support

Genzyme, a Sanofi Company

Ethics review

Status: Approved
Approval date: 15/10/2012
Contact:

Results

• Results available: Yes
• Date Posted: 02/03/2017
• Date Completed: 17/08/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-001966-14/results