A Study of the Effect of Aldurazyme® (Laronidase) Treatment on Lactation in Female Patients With Mucopolysaccharidosis I (MPS I) and Their Breastfed Infants

A Multicenter, Multinational, Open-Label Study of the Effects of Aldurazyme® (Laronidase) Treatment on Lactation in Women With Mucopolysaccharidosis I (MPS I) and Their Breastfed Infants

The purpose of this study is to determine if laronidase is present in the breast milk of post-partum women receiving Aldurazyme® (laronidase) and the effects of Aldurazyme (laronidase) on the growth, development, and immunologic response of their breastfed infants.

Study Overview

• Status: Terminated
• Conditions: Mucopolysaccharidosis I; Hurler's Syndrome; Hurler-Scheie Syndrome; Scheie
• Intervention / Treatment: Biological: Laronidase

Detailed Description

Recruitment is not limited to the facility listed; facilities not yet active may be added upon identification of a patient.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Medical Information; Phone Number: 800-745-4447; Email: MedInfo@genzyme.com
• Study Contact Backup: Name: Medical Information; Phone Number: 617-252-7832; Email: MedInfo@genzyme.com

Study Locations

• Italy
  • Rome, Italy
    • Dipartimento di Scienze Pediatriche Medico - Chirurgiche e Neuro Scienze dello Suiluppo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (Mothers):

• The patient must have a documented laronidase deficiency with a fibroblast, plasma, serum, leukocyte, or dried blood spot laronidase enzyme activity assay.
• Be pregnant, planning to breastfeed post-partum, and receiving Aldurazyme (laronidase) therapy while breastfeeding.
• Provide signed, written informed consent prior to any protocol-related procedures. Consent of a legally authorized guardian(s) is (are) required for mothers younger than 18 years of age. If a mother is under 18 years old and can understand the consent, written informed consent is required from both the mother and the authorized guardian(s).
• Provide signed, written informed consent for their infants to participate as study patients. If a mother is younger than 18 years of age, consent for mother and infant will be obtained from the legal guardian.

Exclusion Criteria (Mothers and Infants):

• Have a medical condition, serious intercurrent illness, or other extenuating circumstance that may interfere with study compliance, including all prescribed evaluations and follow-up activities.
• Have received an investigational drug within 30 days prior to study enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Laronidase; Mothers treated with laronidase who intended to breastfeed their infants while receiving laronidase and their infants who were breastfeed while the mothers were receiving laronidase.	Biological: Laronidase; dose of 0.58mg/kg body weight intravenously (IV) every week; Other Names: Aldurazyme; Recombinant human alpha L iduronidase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Lactating Women With Serum IgG Antibodies to Laronidase		Up to 18 months
Amount of IgG Antibody Titers to Laronidase in Lactating Women		Baseline and Week 12
Number of Women Who Breastfed		Up to 18 months
Number of Women Who Were Successful at Breastfeeding		Up to 18 months
Number of Women Whose Breast Milk Contains Laronidase		Up to 18 months
Amount of Laronidase in the Breast Milk of Lactating Mothers With Mucopolysaccharidosis I (MPS I) Disease		Up to 18 months
Number of Women With Abnormal Urine Glycosaminoglycans (uGAG) Levels		Up to 18 months
Amount of uGAG in the Urine of Women	Urine samples were collected at specified intervals to measure uGAG in the urine of women. Reference range of uGAG between 2.64 - 37.65 was considered as normal. mg/g creatinine = milligram per gram of creatinine.	Baseline and Week 12
Number of Participants With Medical History of the Mother: Pre-Existing Conditions		Baseline
Physical Examination Findings of the Mother	Physical examination was performed at specified intervals. Physical examination included the following physical observations: general appearance, skin, head, ears, eyes, nose, and throat, lymph nodes, abdomen, extremities/joints, neurological, mental status, and the following, if appropriate, breasts, external genitalia, pelvic, and rectal.	Up to 18 months
Temperature of the Mother		Baseline and Week 12
Heart Rate of the Mother		Baseline and Week 12
Respiratory Rate of the Mother		Baseline and Week 12
Blood Pressure of the Mother	Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at specified timepoints.	Baseline and Week 12
Weight of the Mother		Baseline and Week 12
Height of the Mother		Baseline
Number of Infants With Abnormal uGAG Levels		Up to 72 weeks
Amount of uGAG in the Urine of Infants	Urine samples were collected at specified intervals to measure uGAG in the urine of infant. Reference range of uGAG between 30 - 300 was considered as normal.	Baseline, Week 12, Week 24, Week 36, Week 48, Week 60, and Week 72
Number of Participants With Medical History of the Infant:Pre-Existing Conditions		Baseline
Number of Infants With Abnormal Physical Finding	Physical examination included the following physical observations: general appearance, skin, lymph nodes, heart, lungs, abdomen, extremities/joints, neurological, mental status, breasts, external genitalia, pelvic, rectal, and Heent.	Baseline, Week 12, Week 24, Week 36, Week 48, and Week 72
Heart Rate of the Infant	Heart rate was measured at specified timepoints.	Baseline, Week 12, Week 24, Week 36, Week 48, and Week 72
Respiratory Rate of the Infant	Respiratory rate was measured at specified timepoints.	Baseline, Week 12, Week 24, Week 36, Week 48, and Week 72
Blood Pressure of the Infant	Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at specified timepoints.	Baseline, Week 12, Week 24, Week 36, Week 48, and Week 72
Weight of the Infant		Baseline, Week 12, Week 24, Week 36, Week 48, and Week 72
Height of the Infant		Baseline, Week 12, Week 24, Week 36, Week 48, and Week 72
Temperature of the Infant		Baseline, Week 12, Week 24, Week 36, Week 48, and Week 72
Head Circumference of the Infant		Baseline, Week 12, Week 24, Week 36, Week 48, and Week 72
Number of Participants With Normal Overall Assessment Measured Using Denver II Developmental Screening Scores	Infant development was assessed with the Denver II Developmental Screening Test. It consisted of 5 areas/subscore i.e., test behavior, personal-social, fine motor, language, and gross motor. The number of participants with normal overall assessment measured using Denver II Developmental Screening Scores have been reported by visit.	Week 12, Week 24, Week 36, Week 48, and Week 72
Number of Infants With IgM and IgG Antibodies to Laronidase Present at Any Time Point		Baseline, Week 12, Week 24, Week 36, and Week 72
Time to Development of IgM and IgG Antibodies to Laronidase		up to Week 72
Amount of IgG and IgM Antibody Titers to Laronidase		Baseline, Week 12, Week 24, Week 36, and Week 72

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company
• Collaborators: BioMarin/Genzyme LLC
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

General Publications

• Castorina M, Antuzzi D, Richards SM, Cox GF, Xue Y. Successful pregnancy and breastfeeding in a woman with mucopolysaccharidosis type I while receiving laronidase enzyme replacement. therapy. Clin Exp Obstet Gynecol. 2015;42(1):108-13.

Helpful Links

• Successful pregnancy and breastfeeding in a woman with mucopolysaccharidosis type I while receiving laronidase enzyme replacement therapy

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2010
• Primary Completion (Actual): December 21, 2022
• Study Completion (Actual): December 21, 2022

Study Registration Dates

• First Submitted: January 3, 2007
• First Submitted That Met QC Criteria: January 4, 2007
• First Posted (Estimated): January 5, 2007

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Syndrome; Mucopolysaccharidoses; Mucopolysaccharidosis I
• Other Study ID Numbers: OBS12874; 2007-007003-33 (EudraCT Number); ALID01803 (Other Identifier: company study code)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org