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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT01951989
Other study ID # CHU-0167
Secondary ID 2012-019622-13
Status Recruiting
Phase Phase 2
First received September 2, 2013
Last updated September 24, 2013
Start date November 2012
Est. completion date June 2016

Study information

Verified date September 2013
Source University Hospital, Clermont-Ferrand
Contact Patrick LACARIN
Phone 04 73 75 11 95
Email placarin@chu-clermontferrand.fr
Is FDA regulated No
Health authority France: Ministry of Health
Study type Interventional

Clinical Trial 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).


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).


Recruitment information / eligibility

Status Recruiting
Enrollment 60
Est. completion date June 2016
Est. primary completion date February 2016
Accepts healthy volunteers No
Gender Both
Age group 12 Years and older
Eligibility 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
Imiglucérase (drug) pharmacokinetics


Locations

Country Name City State
France CHU Clermont-Ferrand Clermont-Ferrand

Sponsors (1)

Lead Sponsor Collaborator
University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. at day 1 No
Secondary Residual rate Pharmacokinetics descriptive criteria are the area under curve at balance, the terminal half-life and the residual rate. every 6 months during 2 years. No
Secondary Endogeneous intra-monocyte glucocérébrosidase activity from untreated patients every 6 months during 2 years No
Secondary 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
at D0, M3, M6 and every 6 months during 2 years: No
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