-Added information on Ora-Blend® and provided instructions for creation of an oral liquid formulation of azathioprine by reconstitution of the tablet with Ora-Blend.

-Increased the CsA dose in order to reach the target subject plasma level of CsA. - Modified the withdrawal rule regarding intravenous infusion antibiotics in recognition that intravenous infusion antibiotics are the treatment of choice in some countries. Thus, the modified rule bases withdrawal not on the type of treatment for an infection (oral versus intravenous) but rather on whether the infection is suspected to be due to the immunosuppressive therapy. - Added information pertaining to labeling, preparation, and storage of investigational products. - Clarified that the types of vaccines and the timing of vaccinations must comply with regional public health requirements. - Modified Inclusion Criterion #2 that the subjects’ parents or legal guardian must be willing and able to comply with the trial procedures. - Added testing for immunization antibodies in order to determine whether booster shots are necessary for subjects. • Specified that measurement of vital signs may be clinically indicated and captured accordingly even if no abnormalities of the vital signs are assessed as infusion-associated reactions. • Specified that immunology testing should not be limited to just testing for medically important events assessed as hypersensitivity reactions because subjects who experience moderate or recurrent reactions (suspected not to represent a hypersensitivity reaction) may become immunoglobulin E positive and subject-specific infusion management and additional immunology testing may be warranted. • Clarified follow-up for adverse event reporting and specified that uncontrolled hypertension is to be reported as a SAE. • Added a review of safety data for Cohort 1 by an independent Data Monitoring Committee before commencement of dosing in Cohort 2. • Updated the schedule of assessments table to reflect the aforementioned changes.

- Specified the use of a local laboratory for the analysis of hematology parameters to provide timely safety information to the Investigator. - Specified the use of a local laboratory for analysis of CsA trough levels to provide timely trough level information to the Investigator. - Clarified that a positive CsA trough level report from the central laboratory was necessary to begin low-dose Aldurazyme infusions. The local laboratory must report that the target level was reached in a sample taken approximately 1 week after the sample tested by the central laboratory. - Added a statement that subjects are to be encouraged to enroll in the MPS I Registry after completing the study.

Details of the new immunosuppressive regimen was added for Cohort 2 : - Extension of the initial dosing period (for both CsA and azathioprine) from 4 weeks to 6 weeks in the Tolerance Induction Period. - Extension of the immunosuppressant step-down period from 4 weeks to 8 weeks, and number of Aldurazyme infusions increased by 6 (i.e., one infusion per each week). - Study duration of 6 weeks was increased. - Full dose of azathioprine was increased from 2.5 mg/kg to 5.0 mg/kg, and the dosing frequency was decreased from every day to every other day. specification that its administration is to be 3 oral doses given at 8-hour intervals. - Added text regarding the 30-day follow-up phone call in the protocol body and the schedule of events, clarified text regarding the use of subjects diary cards for collection of data on immunosuppressant usage, and made consistent the entry criteria contained in the synopsis with that in the body of the document. - Modified Exclusion Criterion #9 to state that subjects with a history of tuberculosis or a positive test for latent tuberculosis will be excluded from the study. - Modified Inclusion Criterion #6 to require that subjects had a documented α-L-iduronidase deficiency based on a fibroblast, plasma, serum, leukocyte, or dried blood spot α-L-iduronidase enzyme activity assay (not a level of ≤10% of the normal mean value of the measuring laboratory). - Added new Exclusion Criterion #3 to prevent enrollment of subjects with a severe hypersensitivity to any of the investigational drugs in the study. - Clarified that the "immune tolerance group" used for statistical comparisons is also called the "final cohort" or the "cohort that received the final regimen". - Corrected and clarified the roles of the Sponsor, Investigator, and Data Monitoring Committee. - Updated the definition of infusion-associated reaction to reflect the current definitions of the Sponsor's Global Pharmacovigilance & Epidemiology group.

- Decreased the maximum number of cohorts from 3 to 2 due to difficulty in recruiting suitable subjects into the study. - Changed the success criteria of a cohort from 4 of 7 evaluable subjects to 3 of 7 evaluable subjects due to updated power calculations, and decreased the maximum number of subjects enrolled from 18 to 12. - Increased the upper age limit to include subjects who were 5 years of age at enrollment or younger. - Removed experimental immune assays as safety assessments for Cohort 2. - Clarified the processes for assessing infusion-associated reactions.