Pharmacokinetics, Pharmacodynamics And Safety Study Of Elelyso(tm) In Pediatric Subjects With Type 1 Gaucher Disease

NCT03021941 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: B3031003
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

In August of 2014, the FDA approved ELELYSO for long-term enzyme replacement therapy (ERT) for pediatric subjects with a confirmed diagnosis of Type 1 Gaucher disease. The recommended dosage for treatment-naïve adult and pediatric subjects 4 years of age and older is 60 units per kg of body weight administered every other week as a 60 to 120 minute intravenous infusion. As a postmarketing commitment, the Sponsor agreed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of Elelyso (taliglucerase alfa) in pediatric subjects with Type 1 Gaucher Disease. in at least 5 subjects with body weight less than 15 kg; at least 5 subjects with body weight 15 to less than 20 kg; and at least 5 subjects with body weight of 20-25 kg with Type 1 Gaucher disease dosed at 60 units/kg every other week. When applicable, PD measurements for children enrolled in the PK study may be obtained through the taliglucerase alfa registry (PMR 1895-5) and will include organ volumes (spleen and liver), hematological values (hemoglobin and platelets) as well as growth (height and weight) data. Safety data, including any serious hypersensitivity reactions, such as anaphylaxis, as well as changes in antibody status (ie, detection and titers of binding and neutralizing antibodies, and detection of IgE antibodies), will also be collected through the taliglucerase alfa registry.

Conditions

Type 1 Gaucher Disease

Keywords

Gaucher Disease; Enzyme Replacement Therapy

Outcome Measures

Primary Outcomes (6)

• Pharmacokinetics - AUCinf

  AUCinf of taliglucerase alfa assessed within 6 months from the subject's first dose of taliglucerase alfa.

  Up to 6 Months

• Pharmacokinetics - AUClast

  AUClast of taliglucerase alfa assessed within 6 months after the subject's first dose of taliglucerase alfa.

  Up to 6 Months

• Pharmockinetics - Cmax

  Cmax of taliglucerase alfa assessed within 6 months after the subject's first dose of taliglucerase alfa.

  Up to 6 Months

• Pharmacokinetics - t½

  t½ of taliglucerase alfa assessed within 6 months after the subject's first dose of taliglucerase alfa.

  Up to 6 Months

• Pharmacokinetics - CL

  CL of taliglucerase alfa assessed within 6 months after the subject's first dose of taliglucerase alfa.

  Up to 6 Months

• Pharmacokinetics - Vss

  Vss of taliglucerase alfa assessed within 6 months after the subject's first dose of taliglucerase alfa.

  Up to 6 Months

Secondary Outcomes (7)

• Pharmacodynamics - Spleen volume/size

  12 Months

• Pharmacodynamics - Liver volume/size

  12 Months

• Pharmacodynamics - Growth measurements

  12 Months

• Pharmacodynamics - Hemoglobin and Platelet Counts

  12 Months

• Safety - Antibody Assessment

  12 Months

Study Arms (1)

Elelyso 60 units/kg

OTHER

All patients receive 60 units/kg of Elelyso.

Drug: Elelyso 60 units/kg

Interventions

Elelyso 60 units/kg DRUG

All patients receive Elelyso 60 units/kg.

Elelyso 60 units/kg

Eligibility Criteria

• Age: Up to 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female pediatric subjects with a diagnosis of Type 1 Gaucher disease (evidence of leukocyte acid-glucosidase activity 30% of the mean of the reference range for healthy persons), and meeting one of three weight categories: less than15 kg; 15 to less than 20 kg or 20-25 kg.
• ERT treatment-naïve, or able to perform the PK assessment within the initial 6 months of initial Elelyso treatment (provided the subject was ERT naïve prior to the start of Elelyso).
• Have had baseline (ie, prior to the first dose of study medication) PD measurements (spleen volume/size measured by MRI, CT or ultrasound, hemoglobin/platelet counts and growth measures including height and weight), immunogenicity sample collection and Gaucher disease diagnosis history documented in advance of treatment start.
• Presence of splenomegaly at baseline defined as spleen volume/size measurement of 5 MN.
• Subjects prescribed the nominal dose of 60 units/kg every two weeks and can tolerate an infusion rate of 1 mL/min.
• Evidence of a personally signed and dated informed consent document from parent/legal guardian (or adult caregiver) capable of providing informed consent indicating that the subject's parent(s)/legal guardian has been informed of all pertinent aspects of the study before any screening procedures are performed. When age appropriate, written assent must also be obtained.
• Have parent/legal guardian (or adult caregiver) capable and willing to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

You may not qualify if:

• Evidence or history of clinically significant issue or the presence of a medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator, would interfere with the subject's participation in the study, cause harm to the subject or decrease compliance with the study requirements.
• Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the PK sample collection visit, whichever is longer.
• A diagnosis of Type 2 or 3 Gaucher disease, or the presence of neurological signs and symptoms characteristic of Type 2 or 3 Gaucher disease.
• Any change during the registry study to the subjects dose of taliglucerase alfa infusion (ie, change from 60 units/kg every two weeks to a different dose of taliglucerase alfa) or a change in infusion duration or rate or a change of ERT medication (ie, switch from taliglucerase alfa to a different ERT).
• In the judgment of the Investigator, the subject's vital signs (eg, blood pressure, pulse) prior to infusion on the day of the PK visit indicate that participation in the study would not be in the study candidate's best interest.
• A hemoglobin level of \<10 g/dL within 30 days of the PK sample visit or on the day of the PK sample visit.
• History of sensitivity to heparin or heparin-induced thrombocytopenia. (Note: applies only if heparin lock or flush is to be used on the day of the PK sample visit).
• Parents or legal guardians who are investigational site staff members directly involved in the conduct of the study and their family members, children of site staff members otherwise supervised by the Investigator, or subjects who are children of Pfizer employees directly involved in the conduct of the study.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

O&O Alpan LLC

Fairfax, Virginia, 22030, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Gaucher Disease

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; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2016
• First Posted: January 16, 2017
• Study Start: July 31, 2019
• Primary Completion: June 30, 2020
• Study Completion: June 30, 2020
• Last Updated: September 24, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)