Study of the Effects of Fabrazyme Treatment on Lactation and Infants

Phase 4

Terminated

Conditions: Fabry Disease
Alpha Galactosidase A Deficiency

Interventions: Drug: agalsidase beta

Registration Number: NCT00230607

Lead Sponsor: Genzyme, a Sanofi Company

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 7

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fabrazyme	agalsidase beta	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.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics: Observed Maximum Plasma Concentration (Cmax) of Alpha-galactosidase A	Month 1, 3, and 6	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.
Pharmacokinetics: Observed Maximum Plasma Concentration of Alpha-galactosidase A in Breast Milk	Month 1, 3 and 6	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.
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	Month 1, 3 and 6	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.
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	Month 1, 3 and 6	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.
Pharmacokinetics: Lactation Clearance of Alpha-galactosidase A	Month 1, 3 and 6	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.
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to 2 Hours (AUC0-2): Milk to Plasma Ratio	Month 1, 3 and 6	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.
Total Volume of Breast Milk	Baseline, Month 2, 6, and 12	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.
Total Fat Content in Breast Milk	Baseline, Month 2, 6, and 12	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.
Total Protein Content in Breast Milk	Baseline, Months 2, 6, and 12	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.
Lactation Status of Mothers at Baseline, Months 1, 2, 3, 4, and 6	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.
Medical History of Enrolled Mothers	Baseline	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.
Genotype of the Enrolled Mothers	Baseline	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.
Pregnancy Outcome	Baseline	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.
Number of Mothers Who Were Seropositive for Anti-Fabrazyme Immunoglobulin G (IgG) Antibodies at Baseline	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.
Medical History of Infants at Baseline	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.
Concentration of Alpha-galactosidase (αGAL) in Plasma	Month 1, 3, and 6	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.
Concentration of Alpha-galactosidase in Breast Milk	Month 1, 3, and 6	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.
Number of Infant Participants With Abnormal Physical Examination	Baseline, Months 1, 2, 4, 6, 12, 18 and 24	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.
Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) Score of Infants at 1 Minute and 5 Minutes After Birth	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.
Growth Response of Infants	Months 1, 2, 3, 6, 12, 18 and 24	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.
Development Response of Infants	Months 1, 2, 3, 6, 12, 18 and 24	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.
Number of Infants Seropositive for Anti-Fabrazyme Immunoglobulin G Antibodies	Baseline, Months 2, 6, and 12	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.
Number of Infants Seropositive for Anti-Fabrazyme Immunoglobulin M Antibodies	Baseline, Months 2, 6, and 12	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.
Genotype of the Infants	Baseline	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.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAEs)	From Baseline (Mother: within 1 month prior to delivery; Infant: at birth) up to Month 24	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.
Number of Participants Who Received Concomitant Medications	From Baseline (Mother: within 1 month prior to delivery; Infant: at birth) up to Month 24	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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (5): investigational site number 04Bodamer
🇦🇹
Marl, Austria
investigational site number 03Waldek
🇬🇧
Salford, United Kingdom
Investigational Site Number 840005
🇺🇸
Decatur, Georgia, United States
Investigational Site Number 840006
🇺🇸
Fairfax, Virginia, United States
investigational site number 01Rhead
🇺🇸
Milwaukee, Wisconsin, United States