A Study Evaluating the Safety and Pharmacokinetics of Aldurazyme® (Laronidase) in MPS I Patients Less Than 5 Years Old

Mucopolysaccharidosis I Clinical Trial

Official title:

A Phase II Open-Label Clinical Trial of Recombinant Human Alpha-L-iduronidase (Aldurazyme®) to Evaluate the Safety and Pharmacokinetics in Mucopolysaccharidosis I (MPS I) Patients Less Than 5 Years Old

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00146757
• Other study ID #: ALID-014-02
• Status: Completed
• Phase: Phase 2
• First received: September 2, 2005
• Last updated: March 17, 2015
• Start date: October 2002
• Est. completion date: May 2005

Study information

• Verified date: March 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The main objectives of this study are to evaluate the safety and pharmacokinetics (PK) of enzyme replacement therapy with recombinant human alpha-L-iduronidase [Aldurazyme® (laronidase)] in mucopolysaccharidosis I (MPS I) patients less than 5 years old. Efficacy measurements will also be evaluated in this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 2005
• Est. primary completion date: May 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 5 Years

Eligibility

Inclusion Criteria:

• Written informed consent is required from the parent(s) or legal guardian(s) prior to any protocol-related procedures being performed. (A separate informed consent will be requested from the parent(s) for their genotyping, which is independent of the inclusion.)

• Be less than 5 years of age at the time of enrollment.

• Have confirmed iduronidase deficiency with a fibroblast or leukocyte alpha-L-iduronidase enzyme activity level of less than 10.0 % of the lower limit of the normal range, or below the detection range of the measuring laboratory.

• Have a clinical diagnosis of MPS I based on genotyping.

• Documentation in his/her medical record that the parent(s) or legal guardian(s) have had counseling or a consultation regarding HSCT in order to assure that the parent(s) or legal guardian(s) are fully informed regarding the risks and benefits of this alternative treatment for patients eligible for the trial and with the severe manifestations of MPS I with neurodegeneration.

Exclusion Criteria:

• The patient is under consideration for or has undergone hematopoietic stem cell transplantation (HSCT).

• The patient has acute hydrocephalus at the time of enrollment.

• The patient has a clinically significant organic disease (with the exception of symptoms relating to MPS I) including: cardiovascular, hepatic, pulmonary, neurologic, or renal disease, other serious intercurrent illness, or extenuating circumstances that, in the opinion of the Investigator, would preclude participation in the trial or potentially decrease survival.

• The patient has received any investigational product within 30 days prior to trial enrollment.

• The patient has known severe hypersensitivity to Aldurazyme® (laronidase) or components of the delivery solution.

Study Design

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

Related Conditions & MeSH terms

• Hurler Syndrome
• Hurler-Scheie Syndrome
• Mucopolysaccharidoses
• Mucopolysaccharidosis I
• Scheie Syndrome
• Syndrome

Intervention

Biological:
• Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
100 U/kg every week
• Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
200 U/kg every week (Week 26 onwards)

Locations

Country	Name	City	State
France	Hôpital E. Herriot	Lyon
Germany	Johannes Gutenberg Universität	Kinderklinik	Mainz
Netherlands	Sophia Children's Hospital	Rotterdam
United Kingdom	Willink Biochemical Genetics Unit Royal Hospital for Children	Manchester

Sponsors (2)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company	BioMarin/Genzyme LLC

Countries where clinical trial is conducted

France,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percent Change From Baseline to Week 52 in Urinary Glycosaminoglycan (uGAG) Level	Percentage change in the concentration of GAG relative to creatinine (ug GAG/mg creatinine) in urine from Baseline to Week 52; A greater decrease in percent change indicates a greater response.	Baseline to 52 weeks	No
Other	Percent Change From Baseline to Week 52 in Liver Size (Hepatomegaly)	Percent change in extent of Liver Edge Below Right Costal Margin (BRCM) measured in centimeters from Baseline to Week 52; A greater decrease in percent change indicates a greater response.	Baseline to 52 weeks	No
Other	Change From Baseline to Week 52 in Apnea/Hypopnea Index (AHI)	Number of absent (apnea) and shallow (hypopnea) breaths per hour of sleep. A greater decrease in events per hour indicates a greater response.	Baseline to 52 weeks	No
Other	Expert Global Assessment of Sleep Study Results at Week 52 Compared With Baseline	Independent experts provided a global assessment for each sleep study visit as well as the degree of clinically meaningful change over the course of the study. Assessment was based on AHI, severity and frequency of oxygen desaturations and sleep quality.	Baseline to 52 weeks	No
Other	Change From Baseline to Week 52 in Left Ventricular Mass (LVM) Z-Score	Change in LVM Z-scores as measured by echocardiography from Baseline to Week 52. Z-score=number of standard deviations from mean. Z-scores greater than +2 and less than -2 are abnormal. A greater decrease in abnormally high z-score indicates a greater response.	Baseline to 52 weeks	No
Other	Change From Baseline to Week 52 in Height	Change in Z-scores for standing height/lying-length-for-age from Baseline to Week 52. Z-score=number of standard deviations from mean. Z-scores greater than +2 and less than -2 are abnormal. A greater decrease in abnormally high z-score indicates a greater response.	Baseline to 52 weeks	No
Other	Investigator's Clinical Assessment at Week 52 Compared With Baseline	The Investigator's impression of the patient's overall clinical status at Week 52 compared with Baseline.	Baseline to 52 weeks	No
Primary	Safety Evaluation	Overall Safety Summary of Adverse Events (AEs) during Treatment Safety assessment was based on the incidence of AE reports.	52 weeks	Yes
Primary	Pharmacokinetics - Area Under the (Plasma Concentration-time) Curve (AUC8)	AUC8 is a measure of the total exposure to a drug.	52 weeks	No
Primary	Pharmacokinetics - Elimination Half Life (t1/2)	Half-life is the time it takes for the concentration of drug in plasma to decline by 50%.	52 weeks	No
Primary	Pharmacokinetics - Total Plasma Clearance (CL)	CL is volume of the body fluid cleared of the drug per unit of time.	52 weeks	No
Primary	Pharmacokinetics - Volume of Distribution (Vz)	Vz is the volume that relates the amount of drug in the body after absorption is complete to the concentration of drug in the plasma.	52 weeks	No