Study of the Effects of Fabrazyme Treatment on Lactation and Infants

A Multicenter, Multinational Study of the Effects of Fabrazyme (Agalsidase Beta) Treatment on Lactation and Infants

The study was planned for up to 2 years (24 months). Planned full participation for both mother and infant was 24 months, planned full participation of mother and development of infant was 24 months, while planned full participation of mother and no infant participation was 6 months.

Study Overview

• Status: Terminated
• Conditions: Fabry Disease; Alpha Galactosidase A Deficiency
• Intervention / Treatment: Drug: agalsidase beta

Detailed Description

NOTE: Estimated Enrollment: 10 mothers and up to 10 infants

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free number for US & Canada); Phone Number: 1 then # 800-633-1610; Email: Contact-US@sanofi.com

Study Locations

• Austria
  • Marl, Austria
    • investigational site number 04Bodamer
• United Kingdom
  • Salford, United Kingdom, M6 8HD
    • investigational site number 03Waldek
• United States
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Investigational Site Number 840005
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Investigational Site Number 840006
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53201-1997
      • investigational site number 01Rhead

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Mothers that met the following criteria were enrolled in this study:

• provided signed written informed consent to participate in this study,
• be enrolled in the Fabry Registry and received Fabrazyme while lactating,
• agreed to adhere to the Fabry Registry recommended schedule of assessments for medical history, pregnancy outcome, genotyping, and antibody testing, and
• agreed to adhere to the schedule of evaluations for this study.

Infants that met the following criteria were enrolled in this study:

• had the signed written informed consent of the parent(s)/legal guardian(s) to participate in this study,
• born to a mother who was receiving Fabrazyme during lactation,
• received breast milk from the mother, and
• had the agreement of the parent(s)/legal guardian(s) to adhere to the schedule of evaluations for this study.

Exclusion Criteria:

• The mother and infant were excluded from this study if the mother 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: Fabrazyme; Mothers with Fabry disease who received commercially available Fabrazyme intravenous infusion as part of the standard of care while lactating/pregnant and their infants who were breastfed while the mothers were receiving Fabrazyme were enrolled in this study.	Drug: agalsidase beta; Pharmaceutical form: powder for reconstitution Route of administration: intravenous; Other Names: Fabrazyme; r-haGAL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of Alpha-galactosidase (αGAL) in Plasma	Plasma concentration of αGAL was analyzed. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Month 1, 3, and 6
Concentration of Alpha-galactosidase in Breast Milk	Concentration of αGAL in breast milk was analyzed. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Month 1, 3, and 6
Pharmacokinetics: Observed Maximum Plasma Concentration (Cmax) of Alpha-galactosidase A	Cmax was defined as the maximum observed concentration in plasma. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Month 1, 3, and 6
Pharmacokinetics: Observed Maximum Plasma Concentration of Alpha-galactosidase A in Breast Milk	Cmax was defined as the maximum observed concentration in breast milk. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Month 1, 3 and 6
Pharmacokinetics: Area Under the Plasma Alpha-galactosidase A Concentration Versus Time Curve From Time Zero to Two Hours Post End of Infusion (AUC0-2plasma) of Fabrazyme	AUC0-2plasma was defined as the area under the plasma concentration versus time curve from time zero to 2 hours post end of infusion, calculated using the trapezoidal method. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Month 1, 3 and 6
Pharmacokinetics: Area Under the Milk Alpha-galactosidase A Concentration Versus Time Curve From Time Zero to Two Hours Post End of Infusion (AUC0-2milk) of Fabrazyme	AUC0-2milk was defined as the area under the milk concentration versus time curve from time zero to 2 hours post-end of infusion, calculated using the trapezoidal method. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Month 1, 3 and 6
Pharmacokinetics: Lactation Clearance of Alpha-galactosidase A	Lactation clearance was determined in the 0 to 2 hours interval, according to the following equation: the amount of αGAL excreted over the sampling period divided by the AUC during the sampling period. AUC was defined as area under the plasma αGAL concentration-time curve from time 0 to 2 hours post-end of infusion. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Month 1, 3 and 6
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to 2 Hours (AUC0-2): Milk to Plasma Ratio	AUC0-2milk was defined as the area under the milk concentration versus time curve from time zero to 2 hours post end of infusion, calculated using the trapezoidal method. AUC0-2plasma was defined as the area under the plasma concentration versus time curve from time zero to 2 hours post end of infusion, calculated using the trapezoidal method. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Month 1, 3 and 6
Total Volume of Breast Milk	Collected breast milk samples were analyzed for total volume. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Baseline, Month 2, 6, and 12
Total Fat Content in Breast Milk	Collected breast milk samples were analyzed for total fat content. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Baseline, Month 2, 6, and 12
Total Protein Content in Breast Milk	Collected breast milk samples were analyzed for total protein content. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Baseline, Months 2, 6, and 12
Lactation Status of Mothers at Baseline, Months 1, 2, 3, 4, and 6	Lactation status of mothers was assessed by asking them the question 'Was the infant breastfed?'. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Baseline, Months 1, 2, 3, 4, and 6
Medical History of Enrolled Mothers	Medical history of enrolled mothers collected from Fabry registry. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Baseline
Genotype of the Enrolled Mothers	Genotype of each enrolled mother was collected from the Fabry registry. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Baseline
Pregnancy Outcome	Pregnancy outcome of each enrolled mother collected from the Fabry registry. Baseline for mothers was defined as within 1 month prior to delivery. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Baseline
Number of Mothers Who Were Seropositive for Anti-Fabrazyme Immunoglobulin G (IgG) Antibodies at Baseline	IgG antibodies data of the enrolled mothers were collected from the Fabry registry. Formation or continued presence of serum IgG antibodies to r-haGAL was considered seropositive. Baseline for mothers was defined as within 1 month prior to delivery. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Baseline
Medical History of Infants at Baseline	Medical history of infants included birth difficulties (i.e., normal or caesarian birth). Baseline for infants was at birth. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Baseline
Number of Infant Participants With Abnormal Physical Examination	Physical examination of the infants included: length, weight, head circumference, vital signs, general appearance, skin, head, ears, eyes, nose, throat, lymph nodes, heart, lungs, abdomen, extremities/joints, neurological mental status and external genitalia. Baseline for infants was at birth. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Baseline, Months 1, 2, 4, 6, 12, 18 and 24
Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) Score of Infants at 1 Minute and 5 Minutes After Birth	The Apgar score is a method to quickly summarize the health of newborn children. The Apgar score is determined by evaluating the newborn baby on five simple criteria: appearance (skin color), pulse (heart rate), grimace (reflex irritability), activity (muscle tone) and respiration on a scale from 0 to 2. Apgar total score (obtained by summing up values from all five items) ranges from 0 to 10 with a score of 0 expressing the worst neonatal status and a score of 10 the best status. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	At 1 minute and 5 minutes after birth
Growth Response of Infants	Effects of Fabrazyme on the growth response of infants born to mothers with Fabry disease, who had received fabrazyme during lactation. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Months 1, 2, 3, 6, 12, 18 and 24
Development Response of Infants	Effects of Fabrazyme on the development response of infants born to mothers with Fabry disease, who had received fabrazyme during lactation. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Months 1, 2, 3, 6, 12, 18 and 24
Number of Infants Seropositive for Anti-Fabrazyme Immunoglobulin G Antibodies	Formation or continued presence of serum IgG antibodies to r-haGAL was considered as seropositive. Baseline for infants was at birth. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Baseline, Months 2, 6, and 12
Number of Infants Seropositive for Anti-Fabrazyme Immunoglobulin M Antibodies	Formation or continued presence of serum IgM antibodies to r-haGAL was considered as seropositive. Blood samples of umbilical cord collected immediately after birth was used for the Baseline assessment. Baseline for infants was at birth. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Baseline, Months 2, 6, and 12
Genotype of the Infants	Genotype testing was conducted on umbilical cord blood to determine diagnosis of Fabry disease. Baseline for infants was at birth. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	Baseline
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAEs)	Adverse event (AE): any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	From Baseline (Mother: within 1 month prior to delivery; Infant: at birth) up to Month 24
Number of Participants Who Received Concomitant Medications	Concomitant medication was any medication, prescription or over-the-counter, taken by a participant during their participation in an investigational study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.	From Baseline (Mother: within 1 month prior to delivery; Infant: at birth) up to Month 24

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2006
• Primary Completion (Actual): February 9, 2024
• Study Completion (Actual): February 9, 2024

Study Registration Dates

• First Submitted: September 29, 2005
• First Submitted That Met QC Criteria: September 29, 2005
• First Posted (Estimated): October 3, 2005

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: aGAL; r-haGAL; Fabry; Fabrazyme; Lysosomal Storage Disorder; alpha Galactosidase A; GL3; Enzyme Replacement Therapy (ERT)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: AGAL02603; 2006-001910-33 (EudraCT Number); MSC12868 (Other Identifier: Sanofi)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No