Immune Tolerance Study With Aldurazyme® (Laronidase)

This study has been completed.
Sponsor:
Collaborator:
BioMarin/Genzyme LLC
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00741338
First received: August 13, 2008
Last updated: June 2, 2014
Last verified: June 2014
Results First Received: June 2, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Mucopolysaccharidosis I
Interventions: Biological: Laronidase
Drug: Cyclosporine A (CsA)
Drug: Azathioprine (Aza)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 2 centers in Brazil and Russia between September 2008 and September 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 7 participants were enrolled, 3 in Cohort 1 and 4 in Cohort 2. Of the 4 participants enrolled in Cohort 2, one participant was screen failure.

Reporting Groups
  Description
Cohort 1 Tolerance Induction Period (TIP): Cyclosporine A (CsA) starting at 5 milligram per kilogram (mg/kg) orally three times daily until the target trough concentration of at least 350 nanogram per milliliter (ng/mL) (preferably 400 ng/mL) achieved along with azathioprine (Aza) 2.5 mg/kg/day orally. Once target CsA trough level achieved and maintained for at least 1 week, participants received laronidase 0.058 mg/kg (low-dose) once weekly intravenous (IV) infusion (starting from Day 1) up to Week 12. CsA and Aza were gradually discontinued. Immune Challenge Period (ICP): following TIP, laronidase dose increased to 0.12 mg/kg once weekly IV infusion for 1 week followed by 0.25 mg/kg once weekly IV infusion for 1 week and then 0.58 mg/kg (full-dose) once weekly IV infusion up to Week 39.
Cohort 2 TIP: CsA starting at 6.7 mg/kg orally three times daily until the target trough concentration of at least 350 ng/mL (preferably 400 ng/mL) achieved along with Aza 5 mg/kg orally every other day. Once target CsA trough level achieved and maintained for at least 1 week, participants received laronidase 0.058 mg/kg (low-dose) once weekly IV infusion (starting from Day 1) up to Week 18. CsA and Aza were gradually discontinued. ICP: following TIP, laronidase dose increased to 0.12 mg/kg once weekly IV infusion for 1 week followed by 0.25 mg/kg once weekly IV infusion for 1 week and then 0.58 mg/kg (full-dose) once weekly IV infusion up to Week 45.

Participant Flow:   Overall Study
    Cohort 1     Cohort 2  
STARTED     3     3  
COMPLETED     3     2  
NOT COMPLETED     0     1  
Adverse Event                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis population included all enrolled participants, including 1 participant who was screen failure.

Reporting Groups
  Description
Cohort 1 Tolerance Induction Period (TIP): Cyclosporine A (CsA) starting at 5 milligram per kilogram (mg/kg) orally three times daily until the target trough concentration of at least 350 nanogram per milliliter (ng/mL) (preferably 400 ng/mL) achieved along with azathioprine (Aza) 2.5 mg/kg/day orally. Once target CsA trough level achieved and maintained for at least 1 week, participants received laronidase 0.058 mg/kg (low-dose) once weekly intravenous (IV) infusion (starting from Day 1) up to Week 12. CsA and Aza were gradually discontinued. Immune Challenge Period (ICP): following TIP, laronidase dose increased to 0.12 mg/kg once weekly IV infusion for 1 week followed by 0.25 mg/kg once weekly IV infusion for 1 week and then 0.58 mg/kg (full-dose) once weekly IV infusion up to Week 39.
Cohort 2 TIP: CsA starting at 6.7 mg/kg orally three times daily until the target trough concentration of at least 350 ng/mL (preferably 400 ng/mL) achieved along with Aza 5 mg/kg orally every other day. Once target CsA trough level achieved and maintained for at least 1 week, participants received laronidase 0.058 mg/kg (low-dose) once weekly IV infusion (starting from Day 1) up to Week 18. CsA and Aza were gradually discontinued. ICP: following TIP, laronidase dose increased to 0.12 mg/kg once weekly IV infusion for 1 week followed by 0.25 mg/kg once weekly IV infusion for 1 week and then 0.58 mg/kg (full-dose) once weekly IV infusion up to Week 45.
Total Total of all reporting groups

Baseline Measures
    Cohort 1     Cohort 2     Total  
Number of Participants  
[units: participants]
  3     4     7  
Age  
[units: years]
Mean ( Full Range )
  2.60  
  ( 1.8 to 3.5 )  
  3.77  
  ( 3.0 to 4.2 )  
  3.18  
  ( 1.8 to 4.2 )  
Gender  
[units: participants]
     
Female     2     0     2  
Male     1     4     5  



  Outcome Measures
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1.  Primary:   Number of Participants Who Achieved Immune Tolerance Induction   [ Time Frame: 24 weeks after start of full-dose laronidase therapy ]

2.  Secondary:   Percent Reduction of Urinary Glycosaminoglycan (uGAG) Level From Baseline to the End of Treatment/Early Withdrawal   [ Time Frame: Baseline, end of treatment/early withdrawal (up to 24 weeks after start of full-dose laronidase therapy) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Study was discontinued on September 10,2013 due to changing standards of care for this population, practical infeasibility of routinely monitoring plasma CsA in clinical setting, inconclusive results of interim analysis and not due to safety concern.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Trial Transparency Team
Organization: Sanofi
e-mail: Contact-us@sanofi.com


No publications provided


Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00741338     History of Changes
Other Study ID Numbers: ALID02307, 2007-001163-30
Study First Received: August 13, 2008
Results First Received: June 2, 2014
Last Updated: June 2, 2014
Health Authority: Brazil: National Health Surveillance Agency
Russia: Ministry of Health of Russian Federation
United States: Food and Drug Administration