Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease

NCT01410890 | Completed Phase 4 Results DMC

• 3 other identifiers: AGLU077102010-022231-11MSC12790
• Study Type: interventional
• Target: 21
• Locations: 6 countries
• Sites: 12

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.

Conditions

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

Outcome Measures

Primary Outcomes (7)

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (7)

• Pharmacokinetics: Maximum Observed Plasma Concentration of Alglucosidase Alfa in Anti-Recombinant Human Acid Alpha-Glucosidase Antibody Positive and Negative Participants

  Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

• Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration in Anti-rhGAA Antibody Positive and Negative Participants

  Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

• Pharmacokinetics: Terminal Elimination Half-life of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants

  Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

• 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

  Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

• 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

  Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Study Arms (1)

Alglucosidase alfa

EXPERIMENTAL

Participants received intravenous (IV) infusion of Alglucosidase alfa 20 milligrams per kilogram (mg/kg) body weight on Day 1. Infusion was administered at an initial rate of approximately 1 milligram per kilogram per hour (mg/kg/hr) with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of infusion-associated reactions (IARs), until a maximum rate of approximately 7 mg/kg/hr was reached.

Biological: alglucosidase alfa

Interventions

alglucosidase alfa BIOLOGICAL

Intravenous (IV) infusion of 20mg/kg body weight every other week (qow)

Also known as: Lumizyme

Alglucosidase alfa

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (12)

Investigational Site Number 840008

Valhalla, New York, 10595, United States

Location

Investigational Site Number 840007

Cincinnati, Ohio, 45219, United States

Location

Investigational Site Number 840005

Salt Lake City, Utah, 84108, United States

Location

Investigational Site Number 840003

Fairfax, Virginia, 22030, United States

Location

Investigational Site Number 1028

Sofia, 1113, Bulgaria

Location

Investigational Site Number 356001

New Delhi, 110 029, India

Location

Investigational Site Number 356002

Vellore, 632004, India

Location

Investigational Site Number 643001

Moscow, 125367, Russia

Location

Investigational Site Number 643002

Moscow, 125412, Russia

Location

Investigational Site Number 804001

Kiev, 01135, Ukraine

Location

Investigational Site Number 826003

Birmingham, B4 6NH, United Kingdom

Location

Investigational Site Number 826002

Salford, M6 8HD, United Kingdom

Location

Related Publications (1)

• Nicolas X, Hurbin F, Periquet M, Richards S, Sensinger C, Welch K, An Haack K. Pharmacokinetics of Alglucosidase Alfa Manufactured at the 4000-L Scale in Participants with Pompe Disease: A Phase 3/4 Open-Label Study. Clin Pharmacol Drug Dev. 2023 Dec;12(12):1185-1193. doi: 10.1002/cpdd.1314. Epub 2023 Sep 13.

  PMID: 37705424 DERIVED

MeSH Terms

Conditions

Glycogen Storage Disease Type II

Interventions

GAA protein, human

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

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: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2011
• First Posted: August 5, 2011
• Study Start: November 3, 2014
• Primary Completion: November 20, 2020
• Study Completion: November 20, 2020
• Last Updated: March 28, 2022
• Results First Posted: June 11, 2021

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

GB (2); UA (1); US (4); RU (2); IN (2); BU (1)