Intra-monocyte Imiglucerase Kinetics in Gaucher Disease
Information source: University Hospital, Clermont-Ferrand
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Gaucher Disease
Intervention: Imiglucérase (drug) pharmacokinetics (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: University Hospital, Clermont-Ferrand Official(s) and/or principal investigator(s): Marc BERGER, Principal Investigator, Affiliation: University Hospital, Clermont-Ferrand
Overall contact: Patrick LACARIN, Phone: 04 73 75 11 95, Email: placarin@chu-clermontferrand.fr
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).
Clinical Details
Official title: Study of Intra-monocytic Imiglucerase Kinetic and Its Correlation With Clinical and Biological Gaucher Disease
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Enzyme intra-monocyte activity (sum of endogenous enzyme activities and therapeutic enzyme)in patients treated with imiglucerase
Secondary outcome: Residual rateEndogeneous intra-monocyte glucocérébrosidase activity from untreated patients Biomarker dosages will provide serum concentration values
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
Minimum age: 12 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Patrick LACARIN, Phone: 04 73 75 11 95, Email: placarin@chu-clermontferrand.fr
CHU Clermont-Ferrand, Clermont-Ferrand 63003, France; Recruiting Patrick LACARIN, Phone: 04 73 75 11 95, Email: placarin@chu-clermontferrand.fr Marc BERGER, Principal 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, Sub-Investigator
Additional Information
Starting date: November 2012
Last updated: September 24, 2013
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