Intra-monocyte Imiglucerase Kinetics in Gaucher Disease

NCT01951989 | Unknown Phase 2

• 2 other identifiers: CHU-01672012-019622-13
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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).

Conditions

Gaucher Disease

Keywords

Gaucher disease; Imiglucerase; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Residual rate

  every 6 months during 2 years.

• Endogeneous intra-monocyte glucocérébrosidase activity from untreated patients

  every 6 months during 2 years

• Biomarker dosages will provide serum concentration values

  at D0, M3, M6 and every 6 months during 2 years:

Study Arms (1)

Imiglucerase

EXPERIMENTAL

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

Interventions

Imiglucérase (drug) pharmacokinetics DRUG

Imiglucerase

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients must have a social security system

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (1)

CHU Clermont-Ferrand

Clermont-Ferrand, 63003, France

RECRUITING

MeSH Terms

Conditions

Gaucher Disease

Interventions

Pharmaceutical Preparations; Pharmacokinetics

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Metabolism; Pharmacological and Toxicological Phenomena; Physiological Phenomena

Study Officials

• Marc BERGER

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrick LACARIN

CONTACT

04 73 75 11 95; placarin@chu-clermontferrand.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2013
• First Posted: September 27, 2013
• Study Start: November 1, 2012
• Primary Completion: February 1, 2016
• Study Completion: June 1, 2016
• Last Updated: September 27, 2013

Record last verified: 2013-09

Locations

FR (1)