Clinical trial NCT01951989: Intra-monocyte Imiglucerase Kinetics in Gaucher Disease
Official title: Study of Intra-monocytic Imiglucerase Kinetic and Its Correlation With Clinical and Biological Gaucher Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Gaucher Disease
Keywords: Gaucher disease
Imiglucerase
Pharmacokinetics
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2013-09-27
Enrollment: 60
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Enzyme intra-monocyte activity (sum of endogenous enzyme activities and therapeutic enzyme)in patients treated with imiglucerase
timeFrame: at day 1
Secondary outcomes:
measure: Residual rate
timeFrame: every 6 months during 2 years.
measure: Endogeneous intra-monocyte glucocérébrosidase activity from untreated patients
timeFrame: every 6 months during 2 years
measure: Biomarker dosages will provide serum concentration values
timeFrame: at D0, M3, M6 and every 6 months during 2 years:
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Marc BERGER
role: PRINCIPAL_INVESTIGATOR
References: