Clinical trial NCT01712178: A Study in Rheumatoid Arthritis (RA) Patients to Compare Two Formulations of Adalimumab for Pharmacokinetic, Pharmacodynamic and Safety
Official title: Study to Assess the Pharmacokinetic, Pharmacodynamic, Safety and Immunogenicity of a New Adalimumab Formulation in Subjects With Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Pharmacodynamic,Pharmacokinetic
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2012-10-23
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study in Rheumatoid Arthritis (RA) patients to evaluate two formulations of adalimumab for pharmacodynamics, pharmacokinetics, and safety.


Eligibility criteria: Inclusion Criteria:

* Male or female subject, 18 years or older who has a diagnosis of Rheumatoid Arthritis (RA) as defined by the 1987-revised American College of Rheumatology (ACR)-classification criteria or the new American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) diagnostic criteria for RA 2010-classification criteria and has a disease duration for a minimum of 3 months.
* Subjects must be naïve to biologic therapy.
* Subject must meet the following criteria for the joint assessment: • At least 6 swollen joints out of 66 assessed. • At least 6 tender joints out of 68 assessed.
* Prior Disease Modifying Antirheumatic Drug (DMARD) therapy: a) Subjects not on methotrexate at baseline must remain without methotrexate throughout the study. Subjects on prior Methotrexate (MTX) must have discontinued at least 28 days prior to Week 0 (Day 1). b) Subjects on Disease Modifying Antirheumatic Drug (DMARD) therapy other than Methotrexate (MTX) (except prednisone/prednisolone less than or equal to 10 mg) must discontinue it for at least 28 days before the first dose of investigational product at Week 0 (Day 1).
* Female subjects are either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy and/or hysterectomy), or are practicing at least 1 of the following methods of birth control throughout the study and for at least 150 days after the last dose of study drug: • Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD). • Hormonal contraceptives for 90 days prior to study drug administration. • Vasectomized partner(s).
* Subjects must be able and willing to self-administer subcutaneous (SC) injections or have a qualified person available to administer subcutaneous (SC) injections.
* Subject is judged to be in good general health as determined by the Principal Investigator based upon the results of medical history, physical examination, laboratory profile, chest x-ray (CXR), and 12 lead electrocardiogram (ECG) performed during Screening.
* Subject has a negative Tuberculosis (TB) screening assessment (including a (Purified Protein Derivative (PPD) test or QuantiFERON-Tuberculosis (TB) Gold test or equivalent) and negative chest x-ray (Posterior-Anterior (PA) and lateral view) at Screening. If a subject has evidence of a latent Tuberculosis (TB) infection, the subject must initiate and complete a minimum of 2 weeks of anti-Tuberculosis (TB) therapy or have documented completion of a course of anti-Tuberculosis (TB) therapy prior to Baseline.
* Subjects must be willing to provide written consent and to comply with the requirements of this study protocol.

Exclusion Criteria:

* Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks from Baseline visit. Inhaled corticosteroids for stable medical conditions are allowed. Oral of less than or equal to 10 mg/d prednisone equivalent are allowed.
* Subject has been treated with any investigational drug of a chemical or biological nature within a minimum of 30 days or 5 half-lives (whichever is longer) of the drug prior to Baseline Visit.
* Subject has a history of acute inflammatory joint disease of different origin other than Rheumatoid Arthritis (RA) (e.g., seronegative spondyloarthropathy, psoriatic arthritis, Reiter's syndrome, systemic lupus erythematosus, gouty arthritis, or any arthritis with onset prior to age 17 years).
* Known hypersensitivity to adalimumab or its excipients.
* Subject currently uses or plans to use anti-retroviral therapy at any time during the study.
* History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of demyelinating disease.
* History of invasive infection (e.g., listeriosis and histoplasmosis), human immunodeficiency syndrome (HIV).
* Chronic recurring infections or active Tuberculosis (TB).
* History of moderate to severe congestive heart failure (New York Heart Association (NYHA) class III or IV), recent cerebrovascular accident and any other condition which, in the opinion of the investigator, would put the subject at risk by participation in the protocol.
* Evidence of dysplasia or history of malignancy (including lymphoma and leukemia) other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
* Subject received any live vaccine within 3 months prior to study drug administration. - Subject has a history of clinically significant hematologic (e.g., severe anemia, leukopenia, thrombocytopenia), renal or liver disease (e.g., fibrosis, cirrhosis, hepatitis).
* Positive pregnancy test at Screening or Baseline.
* Subject is considered by the investigator, for any reason, to be unsuitable candidate for the study

Primary outcomes:
measure: Serum Concentrations of Adalimumab at Weeks 12 and 24
timeFrame: Measured at Weeks 12 and 24
measure: Mean Disease Activity Scores (DAS28) at Weeks 12 and 24
timeFrame: Measured at Weeks 12 and 24
Secondary outcomes:
measure: Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Weeks 12 and 24
timeFrame: Measured at Weeks 12 and 24
measure: Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Weeks 12 and 24
timeFrame: Measured at Weeks 12 and 24
measure: Mean Health Assessment Questionnaire (HAQ-DI) Scores at Weeks 12 and 24
timeFrame: Measured at Weeks 12 and 24
measure: Mean Short Form-36 (SF-36) Physical Component Summary Scores and Mental Component Summary Scores at Weeks 12 and 24
timeFrame: Measured at Weeks 12 and 24
measure: Percentage of Participants Positive for Anti-adalimumab Antibody
timeFrame: Measured through Week 24
measure: Number of Participants With Adverse Events
timeFrame: From time of informed consent to 70 days following the last dose of study drug
measure: Mean Injection Site Pain on a Visual Analogue Scale (VAS)
timeFrame: Immediately after injections on Day 1
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Site Reference ID/Investigator# 75073
state: Arizona
city: Hemet
country: United States
facility: Site Reference ID/Investigator# 75077
state: California
city: Wichita
country: United States
facility: Site Reference ID/Investigator# 75076
state: Kansas
city: Clifton
country: United States
facility: Site Reference ID/Investigator# 75075
state: New Jersey
city: Philadelphia
country: United States
facility: Site Reference ID/Investigator# 83133
state: Pennsylvania
city: Charleston
country: United States
facility: Site Reference ID/Investigator# 75074
state: South Carolina
city: Brussels
country: Belgium
facility: Site Reference ID/Investigator# 75100
city: Liege
country: Belgium
facility: Site Reference ID/Investigator# 75101
city: Brno
country: Czech Republic
facility: Site Reference ID/Investigator# 75104
city: Prague 2
country: Czech Republic
facility: Site Reference ID/Investigator# 76788
city: Uherske Hradiste
country: Czech Republic
facility: Site Reference ID/Investigator# 75102
city: Zlin
country: Czech Republic
facility: Site Reference ID/Investigator# 75103
city: Ratingen
country: Germany
facility: Site Reference ID/Investigator# 78014
city: Caguas
country: Puerto Rico
facility: Site Reference ID/Investigator# 75079
city: Vega Baja
country: Puerto Rico
facility: Site Reference ID/Investigator# 75078
city: Bucharest
country: Romania
facility: Site Reference ID/Investigator# 76787
city: Cluj-Napoca
country: Romania
facility: Site Reference ID/Investigator# 75978
city: Ploiesti
country: Romania
facility: Site Reference ID/Investigator# 76433
city: Banska Bystrica
country: Slovakia
facility: Site Reference ID/Investigator# 76934
city: Senica
country: Slovakia
facility: Site Reference ID/Investigator# 76935
city: Zilina
country: Slovakia
facility: Site Reference ID/Investigator# 76682
Study officials:
affiliation: AbbVie
name: Andy Payne, PhD
role: STUDY_DIRECTOR
References: