Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease

Pompe Disease Clinical Trial

— PAPAYA  

Official title:

A Phase 3/4 Prospective Study to Characterize the Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01410890
• Other study ID #: AGLU07710
• Secondary ID: 2010-022231-11MS
• Status: Completed
• Phase: Phase 4
• Start date: November 3, 2014
• Est. completion date: November 20, 2020

Study information

• Verified date: March 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: November 20, 2020
• Est. primary completion date: November 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Glycogen Storage Disease
• Glycogen Storage Disease Type II
• Glycogen Storage Disease Type II (GSD II)
• Pompe Disease

Intervention

Biological:
• alglucosidase alfa
Intravenous (IV) infusion of 20mg/kg body weight every other week (qow)

Locations

Country	Name	City	State
Bulgaria	Investigational Site Number 1028	Sofia
India	Investigational Site Number 356001	New Delhi
India	Investigational Site Number 356002	Vellore
Russian Federation	Investigational Site Number 643001	Moscow
Russian Federation	Investigational Site Number 643002	Moscow
Ukraine	Investigational Site Number 804001	Kiev
United Kingdom	Investigational Site Number 826003	Birmingham
United Kingdom	Investigational Site Number 826002	Salford
United States	Investigational Site Number 840007	Cincinnati	Ohio
United States	Investigational Site Number 840003	Fairfax	Virginia
United States	Investigational Site Number 840005	Salt Lake City	Utah
United States	Investigational Site Number 840008	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Bulgaria,  India,  Russian Federation,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Alglucosidase Alfa	Cmax was defined as maximum observed plasma concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Primary	Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alglucosidase Alfa	Tmax was defined as time to reach maximum observed plasma concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Primary	Pharmacokinetics: Area Under the Plasma Concentration-Time Curve (AUC) of Alglucosidase Alfa	AUC was defined as area under the plasma concentration-time curve from time 0 to 24 hours post-dose.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Primary	Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Alglucosidase Alfa	AUC0-last was defined as area under the concentration-time curve from time 0 to the time of the last quantifiable concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Primary	Pharmacokinetics: Terminal Elimination Half-life (T1/2) of Alglucosidase Alfa	T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Primary	Pharmacokinetics: Total Systemic Clearance (CL) of Alglucosidase Alfa	CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Primary	Pharmacokinetics: Volume of Distribution at Steady State (Vss) of Alglucosidase Alfa	Volume of distribution (Vd) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is the apparent volume of distribution at steady-state.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Secondary	Pharmacokinetics: Maximum Observed Plasma Concentration of Alglucosidase Alfa in Anti-Recombinant Human Acid Alpha-Glucosidase Antibody Positive and Negative Participants	Cmax was defined as maximum observed plasma concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Secondary	Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration in Anti-rhGAA Antibody Positive and Negative Participants	Tmax was defined as time to reach maximum observed plasma concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Secondary	Pharmacokinetics: Terminal Elimination Half-life of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants	T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Secondary	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	AUC0-last was defined as area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Secondary	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	AUC0-inf was defined as area under the concentration-time curve from time 0 extrapolated to infinite time.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Secondary	Pharmacokinetics: Total Systemic Clearance in Anti-rhGAA Antibody Positive and Negative Participants	CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Secondary	Pharmacokinetics: Volume of Distribution in Anti-rhGAA Antibody Positive and Negative Participants	Vd is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is the apparent volume of distribution at steady-state.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1