Clinical trial NCT01410890: Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease
Official title: A Phase 3/4 Prospective Study to Characterize the Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pompe Disease
Glycogen Storage Disease Type II (GSD II)
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2011-08-05
Enrollment: 21
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: * The primary objective of this study was to characterize the pharmacokinetics (PK) of alglucosidase alfa manufactured at the 4000 L scale in participants who had a confirmed diagnosis of Pompe disease.
* A secondary objective of this study was to evaluate and explore the relationship between anti-recombinant human acid alpha-glucosidase antibody titers and the PK of alglucosidase alfa.

Detailed description: The total study duration per participant was 4 to 8 weeks that consisted of a screening period (from 2 days to 4 weeks), treatment visit (1 day), and a follow up call (greater than or equal to 30 days). Two participants enrolled prior to protocol amendment 2 (dated 17 December 2015), which changed the study to single-dose, and were treated for 26 weeks, with a 4-week follow up.

Eligibility criteria: Inclusion Criteria:

A participant was to meet all of the following criteria to be eligible for this study:

* The participant and/or the participant's parent/legal guardian was willing and able to provide signed informed consent.
* The participant had a confirmed acid alpha-glucosidase (GAA) enzyme deficiency from skin, blood, or muscle tissue and/or 2 confirmed GAA gene mutations.
* Infant and toddler Pompe disease participants could be included in the study only under condition (minimal body weight) that the trial-related blood loss (including any losses in the maneuver) would not exceed 3 percent (%) of the total blood volume during a period of 4 weeks and would not exceed 1 % at any single time.
* The participant, if female and of childbearing potential, must have had a negative pregnancy test (urine beta-human chorionic gonadotropin) at screening. Note: All female participants of childbearing potential and sexually mature males must have agreed to use a medically accepted method of contraception throughout the study.
* For participants previously treated with alglucosidase alfa the participant had received alglucosidase alfa for at least 6 months.

Exclusion Criteria:

A participant who met any of the following criteria was excluded from this study:

* The participant was participating in another clinical study using an investigational product.
* The participant, in the opinion of the Investigator, was unable to adhere to the requirements of the study.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Alglucosidase Alfa
timeFrame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
measure: Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alglucosidase Alfa
timeFrame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
measure: Pharmacokinetics: Area Under the Plasma Concentration-Time Curve (AUC) of Alglucosidase Alfa
timeFrame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
measure: Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Alglucosidase Alfa
timeFrame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
measure: Pharmacokinetics: Terminal Elimination Half-life (T1/2) of Alglucosidase Alfa
timeFrame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
measure: Pharmacokinetics: Total Systemic Clearance (CL) of Alglucosidase Alfa
timeFrame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
measure: Pharmacokinetics: Volume of Distribution at Steady State (Vss) of Alglucosidase Alfa
timeFrame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Secondary outcomes:
measure: Pharmacokinetics: Maximum Observed Plasma Concentration of Alglucosidase Alfa in Anti-Recombinant Human Acid Alpha-Glucosidase Antibody Positive and Negative Participants
timeFrame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
measure: Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration in Anti-rhGAA Antibody Positive and Negative Participants
timeFrame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
measure: Pharmacokinetics: Terminal Elimination Half-life of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants
timeFrame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
measure: Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants
timeFrame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
measure: Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 and Extrapolated to Infinite Time (AUC0-inf) in Anti-rhGAA Antibody Positive and Negative Participants
timeFrame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
measure: Pharmacokinetics: Total Systemic Clearance in Anti-rhGAA Antibody Positive and Negative Participants
timeFrame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
measure: Pharmacokinetics: Volume of Distribution in Anti-rhGAA Antibody Positive and Negative Participants
timeFrame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Other outcomes:
Locations:
city: Valhalla
country: United States
facility: Investigational Site Number 840008
state: New York
city: Cincinnati
country: United States
facility: Investigational Site Number 840007
state: Ohio
city: Salt Lake City
country: United States
facility: Investigational Site Number 840005
state: Utah
city: Fairfax
country: United States
facility: Investigational Site Number 840003
state: Virginia
city: Sofia
country: Bulgaria
facility: Investigational Site Number 1028
city: New Delhi
country: India
facility: Investigational Site Number 356001
city: Vellore
country: India
facility: Investigational Site Number 356002
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643002
city: Kiev
country: Ukraine
facility: Investigational Site Number 804001
city: Birmingham
country: United Kingdom
facility: Investigational Site Number 826003
city: Salford
country: United Kingdom
facility: Investigational Site Number 826002
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References: