Study of the Effects of Fabrazyme Treatment on Lactation and Infants

NCT00230607 | Terminated Phase 4 Results FDA Drug

• 3 other identifiers: AGAL026032006-001910-33MSC12868
• Study Type: interventional
• Target: 7
• Locations: 3 countries
• Sites: 5

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.

Conditions

Fabry Disease; Alpha Galactosidase A Deficiency

Keywords

alpha Galactosidase A; aGAL; r-haGAL; Fabry; GL3; Fabrazyme; Lysosomal Storage Disorder; Enzyme Replacement Therapy (ERT)

Outcome Measures

Primary Outcomes (26)

• 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

Study Arms (1)

Fabrazyme

EXPERIMENTAL

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

Interventions

agalsidase beta DRUG

Pharmaceutical form: powder for reconstitution Route of administration: intravenous

Also known as: r-haGAL, Fabrazyme

Fabrazyme

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• The mother and infant were excluded from this study if the mother received an investigational drug within 30 days prior to study enrollment.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (5)

Investigational Site Number 840005

Decatur, Georgia, 30033, United States

Location

Investigational Site Number 840006

Fairfax, Virginia, 22030, United States

Location

investigational site number 01Rhead

Milwaukee, Wisconsin, 53201-1997, United States

Location

investigational site number 04Bodamer

Marl, Austria

Location

investigational site number 03Waldek

Salford, M6 8HD, United Kingdom

Location

MeSH Terms

Conditions

Fabry Disease; Lysosomal Storage Diseases

Interventions

agalsidase beta

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Limitations and Caveats

This is a rare disease study, with very few participants enrolled. The study was terminated by the Sponsor. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2005
• First Posted: October 3, 2005
• Study Start: May 28, 2006
• Primary Completion: February 9, 2024
• Study Completion: February 9, 2024
• Last Updated: April 10, 2024
• Results First Posted: April 10, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); AU (1); US (3)