Clinical trial NCT04585711: Pharmacokinetics and Pharmacodynamics of Biologic Drugs in Obese Patients With Arthritis
Official title: Pharmacokinetics and Pharmacodynamics of Biologic Drugs in Obese Patients With Arthritis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Juvenile Idiopathic Arthritis
Rheumatoid Arthritis
Obesity
Keywords: Etanercept
Pharmacokinetics
Pharmacodynamics
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2020-10-14
Enrollment: 30
Sex: ALL
Minimum age (years): 2
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Clearance (CL)
timeFrame: 6 weeks
measure: Volume of distribution (V)
timeFrame: 6 weeks
Secondary outcomes:
measure: Median prediction error between observed and model predicted concentrations
timeFrame: 6 weeks
measure: mean change in DAS28/JADAS27
timeFrame: Baseline, 6 weeks
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke Clinical Research Institute
name: Stephen Balevic, MD
role: PRINCIPAL_INVESTIGATOR
References: