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Intra-monocyte Imiglucerase Kinetics in Gaucher Disease (CIMI)

Primary Purpose

Gaucher Disease

Status
Unknown status
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Imiglucérase (drug) pharmacokinetics
Sponsored by
University Hospital, Clermont-Ferrand
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gaucher Disease focused on measuring Gaucher disease, Imiglucerase, Pharmacokinetics

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patient older than 12 years old with Gaucher disease type 1 or type 3 and having signed an informed consent
  • Treated with imiglucerase (Cerezyme ®) with a stable therapeutic strategy for at least 3 months.

OR

  • Untreated patient, with no therapeutic indication at the time of inclusion and having a diagnosis older than 2 years (non progressive disease)
  • Patients must have a social security system

Exclusion Criteria:

  • Age <12 years old
  • Gaucher disease unproven
  • Gaucher disease treated with therapeutic changes in the previous 3 months, or current treatment different from imiglucerase
  • Gaucher disease untreated whose diagnosis was established for under 2 years

Sites / Locations

  • CHU Clermont-FerrandRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Imiglucerase

Arm Description

Primary purpose: to evaluate the pharmacokinetics of Imiglucerase activity into target cellular compartment depending on dose and frequency of infusions. Secondary purposes : 1) to establish a possible relationship between the intra-monocytic activity of glucocerebrosidase and the clinical and biological activity of Gaucher disease and to define a possible threshold value of enzyme activity; 2) to establish a better correlation with known biomarkers of disease (routine markers and markers recently identified), which would better predict and / or monitor response to treatment ; 3) to compare the residual and natural rate of activity enzyme intra-monocytic for untreated patients (low severity disease).

Outcomes

Primary Outcome Measures

Enzyme intra-monocyte activity (sum of endogenous enzyme activities and therapeutic enzyme)in patients treated with imiglucerase
Enzyme intra-monocyte activity (sum of endogenous enzyme activities and therapeutic enzyme) in patients treated with imiglucerase will be assessed at different times between infusions (8 to 10 time points), and just before an infusion (residual rate). The population pharmacokinetics method allows to perform this analysis in measurement windows that are not necessarily included in the period between two consecutive infusions of imiglucerase but may be spread over several cycles.

Secondary Outcome Measures

Residual rate
Pharmacokinetics descriptive criteria are the area under curve at balance, the terminal half-life and the residual rate.
Endogeneous intra-monocyte glucocérébrosidase activity from untreated patients
Biomarker dosages will provide serum concentration values
1) routine biomarkers (ACE, TRAP, chitotriosidase, ferritin) and 2) potentially interesting biomarkers but not routinely evaluated in France (CCL18, MIP1a, MIP1b, MCP1, IL-8, glycated ferritin). - Gaucher disease status will be assessed by clinical and biological criteria defined by the HAS (Haute Autorité de Santé = High Health Authority). We will consider the two-year periods before and after treatment to identify progressive diseases (clinical or biological significant events associated with Gaucher disease in the two years before and 2 years after the enrolment time

Full Information

First Posted
September 2, 2013
Last Updated
September 24, 2013
Sponsor
University Hospital, Clermont-Ferrand
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1. Study Identification

Unique Protocol Identification Number
NCT01951989
Brief Title
Intra-monocyte Imiglucerase Kinetics in Gaucher Disease
Acronym
CIMI
Official Title
Study of Intra-monocytic Imiglucerase Kinetic and Its Correlation With Clinical and Biological Gaucher Disease
Study Type
Interventional

2. Study Status

Record Verification Date
September 2013
Overall Recruitment Status
Unknown status
Study Start Date
November 2012 (undefined)
Primary Completion Date
February 2016 (Anticipated)
Study Completion Date
June 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Clermont-Ferrand

4. Oversight

5. Study Description

Brief Summary
Rational: Imiglucerase has been used to treat Gaucher disease since 1997 but data about its pharmacokinetics have been partial; investigators know that imiglucerase undergoes a quick clearance from plasma compartment following the infusion (1/2 life: 1-6 min, from tissue: <24h), an observation apparently contradictory with usual infusion rhythm (one infusion every two weeks). Furthermore, by going by GD response, the rhythm of Infusion is sometimes diminished (for example, every 3 or 4 wks) without pharmacological rational ; In parallel, investigators demonstrated that monocytes represent a satisfactory surrogate of GD target cells and that enzyme activity into monocytes varies between individuals. Our hypothesis is that enzyme activity into monocyte compartment could be different and could be related to GD response. Primary purpose: to evaluate the pharmacokinetics of Imiglucerase activity into target cellular compartment depending on dose and frequency of infusions. Secondary purposes : 1) to establish a possible relationship between the intra-monocytic activity of glucocerebrosidase and the clinical and biological activity of Gaucher disease and to define a possible threshold value of enzyme activity; 2) to establish a better correlation with known biomarkers of disease (routine markers and markers recently identified), which would better predict and / or monitor response to treatment ; 3) to compare the residual and natural rate of activity enzyme intra-monocytic for untreated patients (low severity disease).
Detailed Description
Rational: Imiglucerase has been used to treat Gaucher disease since 1997 but data about its pharmacokinetics have been partial; investigators know that imiglucerase undergoes a quick clearance from plasma compartment following the infusion (1/2 life: 1-6 min, from tissue: <24h), an observation apparently contradictory with usual infusion rhythm (one infusion every two weeks). Furthermore, by going by GD response, the rhythm of Infusion is sometimes diminished (for example, every 3 or 4 wks) without pharmacological rational ; In parallel, investigators demonstrated that monocytes represent a satisfactory surrogate of GD target cells and that enzyme activity into monocytes varies between individuals. Our hypothesis is that enzyme activity into monocyte compartment could be different and could be related to GD response. Primary purpose: to evaluate the pharmacokinetics of Imiglucerase activity into target cellular compartment depending on dose and frequency of infusions. Secondary purposes : 1) to establish a possible relationship between the intra-monocytic activity of glucocerebrosidase and the clinical and biological activity of Gaucher disease and to define a possible threshold value of enzyme activity; 2) to establish a better correlation with known biomarkers of disease (routine markers and markers recently identified), which would better predict and / or monitor response to treatment ; 3) to compare the residual and natural rate of activity enzyme intra-monocytic for untreated patients (low severity disease).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gaucher Disease
Keywords
Gaucher disease, Imiglucerase, Pharmacokinetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Imiglucerase
Arm Type
Experimental
Arm Description
Primary purpose: to evaluate the pharmacokinetics of Imiglucerase activity into target cellular compartment depending on dose and frequency of infusions. Secondary purposes : 1) to establish a possible relationship between the intra-monocytic activity of glucocerebrosidase and the clinical and biological activity of Gaucher disease and to define a possible threshold value of enzyme activity; 2) to establish a better correlation with known biomarkers of disease (routine markers and markers recently identified), which would better predict and / or monitor response to treatment ; 3) to compare the residual and natural rate of activity enzyme intra-monocytic for untreated patients (low severity disease).
Intervention Type
Drug
Intervention Name(s)
Imiglucérase (drug) pharmacokinetics
Primary Outcome Measure Information:
Title
Enzyme intra-monocyte activity (sum of endogenous enzyme activities and therapeutic enzyme)in patients treated with imiglucerase
Description
Enzyme intra-monocyte activity (sum of endogenous enzyme activities and therapeutic enzyme) in patients treated with imiglucerase will be assessed at different times between infusions (8 to 10 time points), and just before an infusion (residual rate). The population pharmacokinetics method allows to perform this analysis in measurement windows that are not necessarily included in the period between two consecutive infusions of imiglucerase but may be spread over several cycles.
Time Frame
at day 1
Secondary Outcome Measure Information:
Title
Residual rate
Description
Pharmacokinetics descriptive criteria are the area under curve at balance, the terminal half-life and the residual rate.
Time Frame
every 6 months during 2 years.
Title
Endogeneous intra-monocyte glucocérébrosidase activity from untreated patients
Time Frame
every 6 months during 2 years
Title
Biomarker dosages will provide serum concentration values
Description
1) routine biomarkers (ACE, TRAP, chitotriosidase, ferritin) and 2) potentially interesting biomarkers but not routinely evaluated in France (CCL18, MIP1a, MIP1b, MCP1, IL-8, glycated ferritin). - Gaucher disease status will be assessed by clinical and biological criteria defined by the HAS (Haute Autorité de Santé = High Health Authority). We will consider the two-year periods before and after treatment to identify progressive diseases (clinical or biological significant events associated with Gaucher disease in the two years before and 2 years after the enrolment time
Time Frame
at D0, M3, M6 and every 6 months during 2 years:

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient older than 12 years old with Gaucher disease type 1 or type 3 and having signed an informed consent Treated with imiglucerase (Cerezyme ®) with a stable therapeutic strategy for at least 3 months. OR Untreated patient, with no therapeutic indication at the time of inclusion and having a diagnosis older than 2 years (non progressive disease) Patients must have a social security system Exclusion Criteria: Age <12 years old Gaucher disease unproven Gaucher disease treated with therapeutic changes in the previous 3 months, or current treatment different from imiglucerase Gaucher disease untreated whose diagnosis was established for under 2 years
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Patrick LACARIN
Phone
04 73 75 11 95
Email
placarin@chu-clermontferrand.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc BERGER
Organizational Affiliation
University Hospital, Clermont-Ferrand
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Clermont-Ferrand
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrick LACARIN
Phone
04 73 75 11 95
Email
placarin@chu-clermontferrand.fr
First Name & Middle Initial & Last Name & Degree
Marc BERGER
First Name & Middle Initial & Last Name & Degree
Nadia BELMATOUG
First Name & Middle Initial & Last Name & Degree
Agathe MASSEAU
First Name & Middle Initial & Last Name & Degree
Christine SERRATRICE
First Name & Middle Initial & Last Name & Degree
Christian ROSE
First Name & Middle Initial & Last Name & Degree
Vassili VALAYANNOPOULOS
First Name & Middle Initial & Last Name & Degree
Thierry BILLETTE DE VILLEMEUR
First Name & Middle Initial & Last Name & Degree
Olivier LIDOVE
First Name & Middle Initial & Last Name & Degree
Christian LAVIGNE
First Name & Middle Initial & Last Name & Degree
Pierre KAMINSKY
First Name & Middle Initial & Last Name & Degree
Yves-Marie PERS
First Name & Middle Initial & Last Name & Degree
Catherine CAILLAUD

12. IPD Sharing Statement

Learn more about this trial

Intra-monocyte Imiglucerase Kinetics in Gaucher Disease

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