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

NCT00146757 | Completed Phase 2 Results

• 1 other identifier: ALID-014-02
• Study Type: interventional
• Target: 20
• Locations: 4 countries
• Sites: 4

Brief 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.

Conditions

Mucopolysaccharidosis I; Hurler Syndrome; Hurler-Scheie Syndrome; Scheie Syndrome

Outcome Measures

Primary Outcomes (5)

• Safety Evaluation

  Overall Safety Summary of Adverse Events (AEs) during Treatment Safety assessment was based on the incidence of AE reports.

  52 weeks

• Pharmacokinetics - Area Under the (Plasma Concentration-time) Curve (AUC∞)

  AUC∞ is a measure of the total exposure to a drug.

  52 weeks

• 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

• Pharmacokinetics - Total Plasma Clearance (CL)

  CL is volume of the body fluid cleared of the drug per unit of time.

  52 weeks

• 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

Other Outcomes (7)

• Percent Change From Baseline to Week 52 in Urinary Glycosaminoglycan (uGAG) Level

  Baseline to 52 weeks

• Percent Change From Baseline to Week 52 in Liver Size (Hepatomegaly)

  Baseline to 52 weeks

• Change From Baseline to Week 52 in Apnea/Hypopnea Index (AHI)

  Baseline to 52 weeks

Study Arms (2)

Aldurazyme (rhIDU) 100 U/kg ONLY every week

EXPERIMENTAL

Patients received Aldurazyme (recombinant human alpha-L-iduronidase (rhIDU)) once per week at a dose of 100 Units/kg (approximately 0.58 mg/kg) for up to 52 weeks - labeled dose.

Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)

Aldurazyme (rhIDU) 100-200 U/kg every week

EXPERIMENTAL

After receiving 100 Units/kg dose of Aldurazyme (rhIDU) for the first 25 weeks, patients enrolling after January 1, 2004 were eligible to receive an increased dose of 200 Units/kg from Week 26 onwards if the patient's urinary glycosaminoglycan (uGAG) levels were \>200µg/mg creatinine at Week 22.

Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)

Interventions

Aldurazyme (Recombinant Human Alpha-L-Iduronidase) BIOLOGICAL

100 U/kg every week

Aldurazyme (rhIDU) 100 U/kg ONLY every week

Eligibility Criteria

• Age: Up to 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead
• BioMarin/Genzyme LLC: collaborator

Study Sites (4)

Hôpital E. Herriot

Lyon, France

Location

Johannes Gutenberg Universität

Kinderklinik, Mainz, Germany

Location

Sophia Children's Hospital

Rotterdam, Netherlands

Location

Willink Biochemical Genetics Unit Royal Hospital for Children

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Mucopolysaccharidosis I

Interventions

Iduronidase

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Limitations and Caveats

Due to the rarity of the disease, this study is limited by its small sample size and lack of a control group.

Results Point of Contact

• Title: Genzyme Medical Information
• Organization: Genzyme Corporation

800-745-4447

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 2, 2005
• First Posted: September 7, 2005
• Study Start: October 1, 2002
• Primary Completion: May 1, 2005
• Study Completion: May 1, 2005
• Last Updated: April 3, 2015
• Results First Posted: June 16, 2009

Record last verified: 2015-03

Locations

FR (1); DE (1); NL (1); GB (1)