Intra-monocyte Imiglucerase Kinetics in Gaucher Disease (CIMI)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by University Hospital, Clermont-Ferrand
Sponsor:
Information provided by (Responsible Party):
University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier:
NCT01951989
First received: September 2, 2013
Last updated: September 24, 2013
Last verified: September 2013
  Purpose

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).


Condition Intervention Phase
Gaucher Disease
Drug: Imiglucérase (drug) pharmacokinetics
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study of Intra-monocytic Imiglucerase Kinetic and Its Correlation With Clinical and Biological Gaucher Disease

Resource links provided by NLM:


Further study details as provided by University Hospital, Clermont-Ferrand:

Primary Outcome Measures:
  • Enzyme intra-monocyte activity (sum of endogenous enzyme activities and therapeutic enzyme)in patients treated with imiglucerase [ Time Frame: at day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: every 6 months during 2 years. ] [ Designated as safety issue: No ]
    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 [ Time Frame: every 6 months during 2 years ] [ Designated as safety issue: No ]
  • Biomarker dosages will provide serum concentration values [ Time Frame: at D0, M3, M6 and every 6 months during 2 years: ] [ Designated as safety issue: No ]

    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



Estimated Enrollment: 60
Study Start Date: November 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imiglucerase

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).

Drug: Imiglucérase (drug) pharmacokinetics

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).

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01951989

Contacts
Contact: Patrick LACARIN 04 73 75 11 95 placarin@chu-clermontferrand.fr

Locations
France
CHU Clermont-Ferrand Recruiting
Clermont-Ferrand, France, 63003
Contact: Patrick LACARIN    04 73 75 11 95    placarin@chu-clermontferrand.fr   
Principal Investigator: Marc BERGER         
Sub-Investigator: Nadia BELMATOUG         
Sub-Investigator: Agathe MASSEAU         
Sub-Investigator: Christine SERRATRICE         
Sub-Investigator: Christian ROSE         
Sub-Investigator: Vassili VALAYANNOPOULOS         
Sub-Investigator: Thierry BILLETTE DE VILLEMEUR         
Sub-Investigator: Olivier LIDOVE         
Sub-Investigator: Christian LAVIGNE         
Sub-Investigator: Pierre KAMINSKY         
Sub-Investigator: Yves-Marie PERS         
Sub-Investigator: Catherine CAILLAUD         
Sponsors and Collaborators
University Hospital, Clermont-Ferrand
Investigators
Principal Investigator: Marc BERGER University Hospital, Clermont-Ferrand
  More Information

No publications provided

Responsible Party: University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier: NCT01951989     History of Changes
Other Study ID Numbers: CHU-0167, 2012-019622-13
Study First Received: September 2, 2013
Last Updated: September 24, 2013
Health Authority: France: Ministry of Health

Keywords provided by University Hospital, Clermont-Ferrand:
Gaucher disease
Imiglucerase
Pharmacokinetics

Additional relevant MeSH terms:
Gaucher Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on September 22, 2014