Fabry Disease, Alpha Galactosidase A Deficiency
Conditions
Keywords
alpha Galactosidase A, aGAL, r-haGAL, Fabry, GL3, Fabrazyme, Lysosomal Storage Disorder, Enzyme Replacement Therapy (ERT)
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.
Interventions
DRUGagalsidase beta
Pharmaceutical form: powder for reconstitution Route of administration: intravenous
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
Austria, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 5 active sites in 3 countries. A total of 7 participants were enrolled from 28 May 2006 to 04 March 2022 in this study.
Pre-assignment details
Mothers/pregnant women enrolled in Fabry Registry, who had received Fabrazyme during lactation/pregnancy and infants born to mother who were receiving Fabrazyme during lactation period were enrolled in this study. This is a rare disease study, with very few participants enrolled. Based on the low enrollment number, the study was terminated by the Sponsor. Overall Arm has been reported in participant flow, Baseline and AE section to protect and maintain participant privacy/confidentiality.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 0 |
| Total | 0 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Other | 3 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
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.
Time frame: At 1 minute and 5 minutes after birth
Population: Based on the low enrollment number (2 participants), no data is reported here in order to protect and maintain participant privacy/confidentiality.
Primary
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.
Time frame: Month 1, 3, and 6
Population: Evaluable data was collected for 3 participants only; and thus, was not presented to protect participant confidentiality.
Primary
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.
Time frame: Month 1, 3, and 6
Population: Evaluable data was collected for 3 participants only; and thus, was not presented to protect participant confidentiality.
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.
Time frame: Months 1, 2, 3, 6, 12, 18 and 24
Population: Based on the low enrollment number (2 participants), no data is reported here in order to protect and maintain participant privacy/confidentiality.
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.
Time frame: Baseline
Population: Based on the low enrollment number (5 participants), no data is reported here in order to protect and maintain participant privacy/confidentiality.
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.
Time frame: Baseline
Population: Based on the low enrollment number (2 participants), no data is reported here in order to protect and maintain participant privacy/confidentiality.
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.
Time frame: Months 1, 2, 3, 6, 12, 18 and 24
Population: Based on the low enrollment number (2 participants), no data is reported here in order to protect and maintain participant privacy/confidentiality.
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.
Time frame: Baseline, Months 1, 2, 3, 4, and 6
Population: Evaluable data was collected for 3 participants only; and thus, was not presented to protect participant confidentiality.
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.
Time frame: Baseline
Population: Based on the low enrollment number (5 participants), no data is reported here in order to protect and maintain participant privacy/confidentiality.
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.
Time frame: Baseline
Population: Based on the low enrollment number (2 participants), no data is reported here in order to protect and maintain participant privacy/confidentiality.
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.
Time frame: Baseline, Months 1, 2, 4, 6, 12, 18 and 24
Population: Based on the low enrollment number (2 participants), no data is reported here in order to protect and maintain participant privacy/confidentiality.
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.
Time frame: Baseline, Months 2, 6, and 12
Population: Based on the low enrollment number (2 participants), no data is reported here in order to protect and maintain participant privacy/confidentiality.
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.
Time frame: Baseline, Months 2, 6, and 12
Population: Based on the low enrollment number (2 participants), no data is reported here in order to protect and maintain participant privacy/confidentiality.
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.
Time frame: Baseline
Population: Based on the low enrollment number (5 participants), no data is reported here in order to protect and maintain participant privacy/confidentiality.
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.
Time frame: From Baseline (Mother: within 1 month prior to delivery; Infant: at birth) up to Month 24
Population: Based on the low enrollment number (7 participants), no data is reported here in order to protect and maintain participant privacy/confidentiality.
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.
Time frame: From Baseline (Mother: within 1 month prior to delivery; Infant: at birth) up to Month 24
Population: Based on the low enrollment number (7 participants), no data is reported here in order to protect and maintain participant privacy/confidentiality.
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.
Time frame: Month 1, 3 and 6
Population: Evaluable data was collected for 3 participants only; and thus, was not presented to protect participant confidentiality.
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.
Time frame: Month 1, 3 and 6
Population: Evaluable data was collected for 3 participants only; and thus, was not presented to protect participant confidentiality.
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.
Time frame: Month 1, 3 and 6
Population: Evaluable data was collected for 3 participants only; and thus, was not presented to protect participant confidentiality.
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 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.
Time frame: Month 1, 3 and 6
Population: Evaluable data was collected for 3 participants only; and thus, was not presented to protect participant confidentiality.
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.
Time frame: Month 1, 3, and 6
Population: Evaluable data was collected for 3 participants only; and thus, was not presented to protect participant confidentiality.
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.
Time frame: Month 1, 3 and 6
Population: Evaluable data was collected for 3 participants only; and thus, was not presented to protect participant confidentiality.
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.
Time frame: Baseline
Population: Based on the low enrollment number (5 participants), no data is reported here in order to protect and maintain participant privacy/confidentiality.
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.
Time frame: Baseline, Month 2, 6, and 12
Population: Evaluable data was collected for 3 participants only; and thus, was not presented to protect participant confidentiality.
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.
Time frame: Baseline, Months 2, 6, and 12
Population: Evaluable data was collected for 3 participants only; and thus, was not presented to protect participant confidentiality.
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.
Time frame: Baseline, Month 2, 6, and 12
Population: Evaluable data was collected for 3 participants only; and thus, was not presented to protect participant confidentiality.