Intra-monocyte Imiglucerase Kinetics in Gaucher Disease (CIMI)

University Hospital, Clermont-Ferrand

Status and phase: Unknown; Phase 2

Conditions: Gaucher Disease

Treatments: Drug: Imiglucérase (drug) pharmacokinetics

Study type: Interventional

Funder types: Other

Identifiers

NCT01951989

2012-019622-13

CHU-0167

Details and patient eligibility

About

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).

Full 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).

Enrollment: 60 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Imiglucerase

Experimental group

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).

Treatment:

Drug: Imiglucérase (drug) pharmacokinetics