Study of the Effects of Fabrazyme Treatment on Lactation and Infants

Fabry Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00230607
• Other study ID #: AGAL02603
• Secondary ID: 2006-001910-33MS
• Status: Terminated
• Phase: Phase 4
• Start date: May 28, 2006
• Est. completion date: February 9, 2024

Study information

• Verified date: March 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: February 9, 2024
• Est. primary completion date: February 9, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Alpha Galactosidase A Deficiency
• Fabry Disease

Intervention

Drug:
• agalsidase beta
Pharmaceutical form: powder for reconstitution Route of administration: intravenous

Locations

Country	Name	City	State
Austria	investigational site number 04Bodamer	Marl
United Kingdom	investigational site number 03Waldek	Salford
United States	Investigational Site Number 840005	Decatur	Georgia
United States	Investigational Site Number 840006	Fairfax	Virginia
United States	investigational site number 01Rhead	Milwaukee	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Austria,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of Alpha-galactosidase (aGAL) in Plasma	Plasma concentration of aGAL 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
Primary	Concentration of Alpha-galactosidase in Breast Milk	Concentration of aGAL 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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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 aGAL excreted over the sampling period divided by the AUC during the sampling period. AUC was defined as area under the plasma aGAL 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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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