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Pharmacokinetics and Pharmacodynamics of Biologic Drugs in Obese Patients With Arthritis (PRECISE)

Primary Purpose

Juvenile Idiopathic Arthritis, Rheumatoid Arthritis, Obesity

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Etanercept Optimal dosing
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Juvenile Idiopathic Arthritis focused on measuring Etanercept, Pharmacokinetics, Pharmacodynamics

Eligibility Criteria

2 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  • Diagnosis of Rheumatoid Arthritis (RA) according to the 2010 American College of Rheumatology Classification Criteria (patients greater than or equal to 16 years of age at screening)
  • Diagnosis of Juvenile Idiopathic Arthritis (JIA) according to the International League Against Rheumatism Classification Criteria (children less than 16 years of age at screening)
  • Initiating treatment with etanercept as standard of care by a patient's primary rheumatologist
  • Obese at baseline, defined as a body mass index (BMI) greater than or equal to 30 kg/m2 in subjects greater than or equal to 18 years of age, and a BMI greater than or equal to 95th percentile for age and sex in subjects less than18 years of age
  • Active disease at screening, defined as a DAS28 > 3.2 in adults and JADAS27 > 3.8 in children
  • Patients using oral corticosteroids (<10 mg) or DMARDs must be on a stable dose for at least 4 weeks prior to screening

Exclusion Criteria

  • Receipt of any investigational medical product within the past 12 months
  • Positive urine pregnancy test at screening or planned pregnancy during the study period
  • Prior exposure to etanercept or any other biologic agent within 5 drug half-lives
  • Contraindication to etanercept (e.g., allergy, current or chronic infection [positive tuberculosis screening test, positive hepatitis B surface antigen, positive hepatitis C antibody])
  • Personal history of ever having malignancy, lymphoproliferative disease, or demyelinating disease
  • Screening safety labs with a hemoglobin of ≤ 9 g/dL, white blood cell count <3.0x109L, platelets <125,000 x109L, AST/ALT more than 2x the upper limit of normal, or creatinine > 2 mg/dL for adults and >1 mg/dL for children
  • Evidence of erosive osteoarthritis on plain films (if available at time of screening), or severe osteoarthritis (defined as any anticipated need for joint replacement within the next year) as judged by the primary rheumatologist
  • History of any opportunistic infections, or recent severe infection in the 3 months prior to screening (e.g., hepatitis, pneumonia, pyelonephritis, bacteremia)
  • Heart failure with NYHA classification 3 or more
  • Severe functional impairment status, defined as HAQ >2 and CHAQ >1.75

Sites / Locations

  • Duke University Medical Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Optimal dosing

Arm Description

Obese children (≥ 2 year old) and adults with juvenile idiopathic arthritis (JIA) or Rheumatoid Arthritis (RA) who are starting etanercept as part of their routine medical care.

Outcomes

Primary Outcome Measures

Clearance (CL)
Clearance at steady state as measured by PK sampling
Volume of distribution (V)
Volume of distribution at steady state as measured by PK sampling

Secondary Outcome Measures

Median prediction error between observed and model predicted concentrations
We will use PK/PD models to simulate drug concentration for each individual subject. We measure the error between simulated and observed plasma concentrations.
mean change in DAS28/JADAS27
We will score disease activity using the DAS28 (RA) or JADAS27 (JIA) at baseline and 6 week follow up. We will measure the change in score over 6 weeks.

Full Information

First Posted
October 7, 2020
Last Updated
May 22, 2023
Sponsor
Duke University
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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1. Study Identification

Unique Protocol Identification Number
NCT04585711
Brief Title
Pharmacokinetics and Pharmacodynamics of Biologic Drugs in Obese Patients With Arthritis
Acronym
PRECISE
Official Title
Pharmacokinetics and Pharmacodynamics of Biologic Drugs in Obese Patients With Arthritis
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 1, 2024 (Anticipated)
Primary Completion Date
February 28, 2025 (Anticipated)
Study Completion Date
February 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to learn more about how adult and children's bodies use etanercept and how bodyweight influences how well etanercept works. This study will help us understand the proper dose of etanercept in obese children and adults.
Detailed Description
PRECISE is an open-label, single arm, single-center site study to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of dosing interval-optimized etanercept in obese patients with Rheumatoid Arthritis (RA) and Juvenile Idiopathic Arthritis (JIA). Approximately 30 patients with JIA or RA who are starting etanercept standard-of-care will take part in the study. Eligible patients will have blood collections before and after starting the biologic of interest to assess PK and disease activity. Five (5) blood samples will be collected through a combination of clinic and home visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Juvenile Idiopathic Arthritis, Rheumatoid Arthritis, Obesity
Keywords
Etanercept, Pharmacokinetics, Pharmacodynamics

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Optimal dosing
Arm Type
Other
Arm Description
Obese children (≥ 2 year old) and adults with juvenile idiopathic arthritis (JIA) or Rheumatoid Arthritis (RA) who are starting etanercept as part of their routine medical care.
Intervention Type
Drug
Intervention Name(s)
Etanercept Optimal dosing
Intervention Description
Patients will receive Etanercept on an optimal dose interval over a 6-week period based on a PK/PD model.
Primary Outcome Measure Information:
Title
Clearance (CL)
Description
Clearance at steady state as measured by PK sampling
Time Frame
6 weeks
Title
Volume of distribution (V)
Description
Volume of distribution at steady state as measured by PK sampling
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Median prediction error between observed and model predicted concentrations
Description
We will use PK/PD models to simulate drug concentration for each individual subject. We measure the error between simulated and observed plasma concentrations.
Time Frame
6 weeks
Title
mean change in DAS28/JADAS27
Description
We will score disease activity using the DAS28 (RA) or JADAS27 (JIA) at baseline and 6 week follow up. We will measure the change in score over 6 weeks.
Time Frame
Baseline, 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Diagnosis of Rheumatoid Arthritis (RA) according to the 2010 American College of Rheumatology Classification Criteria (patients greater than or equal to 16 years of age at screening) Diagnosis of Juvenile Idiopathic Arthritis (JIA) according to the International League Against Rheumatism Classification Criteria (children less than 16 years of age at screening) Initiating treatment with etanercept as standard of care by a patient's primary rheumatologist Obese at baseline, defined as a body mass index (BMI) greater than or equal to 30 kg/m2 in subjects greater than or equal to 18 years of age, and a BMI greater than or equal to 95th percentile for age and sex in subjects less than18 years of age Active disease at screening, defined as a DAS28 > 3.2 in adults and JADAS27 > 3.8 in children Patients using oral corticosteroids (<10 mg) or DMARDs must be on a stable dose for at least 4 weeks prior to screening Exclusion Criteria Receipt of any investigational medical product within the past 12 months Positive urine pregnancy test at screening or planned pregnancy during the study period Prior exposure to etanercept or any other biologic agent within 5 drug half-lives Contraindication to etanercept (e.g., allergy, current or chronic infection [positive tuberculosis screening test, positive hepatitis B surface antigen, positive hepatitis C antibody]) Personal history of ever having malignancy, lymphoproliferative disease, or demyelinating disease Screening safety labs with a hemoglobin of ≤ 9 g/dL, white blood cell count <3.0x109L, platelets <125,000 x109L, AST/ALT more than 2x the upper limit of normal, or creatinine > 2 mg/dL for adults and >1 mg/dL for children Evidence of erosive osteoarthritis on plain films (if available at time of screening), or severe osteoarthritis (defined as any anticipated need for joint replacement within the next year) as judged by the primary rheumatologist History of any opportunistic infections, or recent severe infection in the 3 months prior to screening (e.g., hepatitis, pneumonia, pyelonephritis, bacteremia) Heart failure with NYHA classification 3 or more Severe functional impairment status, defined as HAQ >2 and CHAQ >1.75
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Balevic Stephen, MD
Phone
919-668-4544
Email
Stephen.balevic@duke.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Cobbaert Marjan, MPH
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Balevic, MD
Organizational Affiliation
Duke Clinical Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Edna Scarlett

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Pharmacokinetics and Pharmacodynamics of Biologic Drugs in Obese Patients With Arthritis

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