A Study in Rheumatoid Arthritis (RA) Patients to Compare Two Formulations of Adalimumab for Pharmacokinetic, Pharmacodynamic and Safety

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01712178
First received: June 14, 2012
Last updated: June 10, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Rheumatoid Arthritis
Biological: Adalimumab, current formulation
Biological: Adalimumab, new formulation
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Study to Assess the Pharmacokinetic, Pharmacodynamic, Safety and Immunogenicity of a New Adalimumab Formulation in Subjects With Active Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Serum Concentrations of Adalimumab at Weeks 12 and 24 [ Time Frame: Measured at Weeks 12 and 24 ] [ Designated as safety issue: No ]
    Blood samples for adalimumab analysis were collected by venipuncture and serum concentrations of adalimumab were determined using a validated enzyme-linked immunoadsorbent assay (ELISA) method.

  • Mean Disease Activity Scores (DAS28) at Weeks 12 and 24 [ Time Frame: Measured at Weeks 12 and 24 ] [ Designated as safety issue: No ]
    The Disease Activity Score (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission.


Secondary Outcome Measures:
  • Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Weeks 12 and 24 [ Time Frame: Measured at Weeks 12 and 24 ] [ Designated as safety issue: No ]

    American College of Rheumatology 20% (ACR20) response. A participant is a responder if the following 3 criteria for improvement from baseline are met:

    • ≥ 20% improvement in tender joint count;
    • ≥ 20% improvement in swollen joint count; and
    • ≥ 20% improvement in at least 3 of the 5 following parameters:

      • Physician global assessment of disease activity
      • Patient global assessment of disease activity
      • Patient assessment of pain
      • Disability Index of the Health Assessment Questionnaire
      • CRP (Acute phase reactant (Erythrocyte sedimentation rate/C-reactive protein))

  • Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Weeks 12 and 24 [ Time Frame: Measured at Weeks 12 and 24 ] [ Designated as safety issue: No ]

    American College of Rheumatology 50% (ACR50) response. A participant is a responder if the following 3 criteria for improvement from baseline are met:

    • ≥ 50% improvement in tender joint count;
    • ≥ 50% improvement in swollen joint count; and
    • ≥ 50% improvement in at least 3 of the 5 following parameters:

      • Physician global assessment of disease activity
      • Patient global assessment of disease activity
      • Patient assessment of pain
      • Disability Index of the Health Assessment Questionnaire
      • CRP (Acute phase reactant (Erythrocyte sedimentation rate/C-reactive protein))

  • Mean Health Assessment Questionnaire (HAQ-DI) Scores at Weeks 12 and 24 [ Time Frame: Measured at Weeks 12 and 24 ] [ Designated as safety issue: No ]
    The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The minimal clinically important difference (MCID) defined for the HAQ-DI is ≥0.22. HAQ remission indicating normal physical function is defined by HAQ-DI < 0.5.

  • Mean Short Form-36 (SF-36) Physical Component Summary Scores and Mental Component Summary Scores at Weeks 12 and 24 [ Time Frame: Measured at Weeks 12 and 24 ] [ Designated as safety issue: No ]
    The Short Form 36 (SF-36) determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the physical component summary score (PCS) of the SF-36. Items 5-8 primarily contribute to the mental component summary score (MCS) of the SF-36. Scores on each item are summed and averaged (range = 0 (maximum disability) - 100 (no disability). The standard recall period is four weeks.

  • Percentage of Participants Positive for Anti-adalimumab Antibody [ Time Frame: Measured through Week 24 ] [ Designated as safety issue: Yes ]
    Percentage of participants with anti-adalimumab antibody

  • Number of Participants With Adverse Events [ Time Frame: From time of informed consent to 70 days following the last dose of study drug ] [ Designated as safety issue: Yes ]
    An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. See the Reported Adverse Events Section for more details.

  • Mean Injection Site Pain on a Visual Analogue Scale (VAS) [ Time Frame: Immediately after injections on Day 1 ] [ Designated as safety issue: Yes ]
    The Visual Analogue Scale (VAS) consisted of a horizontal 100 mm line, with 0 representing "no pain" and 100 representing "worst possible pain". Participants placed a mark on the line representing their current level of pain immediately after injections on Day 1 of the study.


Enrollment: 100
Study Start Date: June 2012
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: New formulation of adalimumab 40 mg every other week
New formulation adalimumab 40 mg every other week
Biological: Adalimumab, new formulation
New formulation adalimumab 40 mg every other week
Active Comparator: Current formulation adalimumab 40 mg every other week
Current formulation adalimumab 40 mg every other week
Biological: Adalimumab, current formulation
Current formulation adalimumab 40 mg every other week
Other Name: Humira

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01712178

Locations
United States, Arizona
Site Reference ID/Investigator# 75073
Mesa, Arizona, United States, 85202
United States, California
Site Reference ID/Investigator# 75077
Hemet, California, United States, 92543
United States, Kansas
Site Reference ID/Investigator# 75076
Wichita, Kansas, United States, 67203
United States, New Jersey
Site Reference ID/Investigator# 75075
Clifton, New Jersey, United States, 07012
United States, Pennsylvania
Site Reference ID/Investigator# 83133
Philadelphia, Pennsylvania, United States, 19152
United States, South Carolina
Site Reference ID/Investigator# 75074
Charleston, South Carolina, United States, 29406
Belgium
Site Reference ID/Investigator# 75100
Brussels, Belgium, 1200
Site Reference ID/Investigator# 75101
Liege, Belgium, 4000
Czech Republic
Site Reference ID/Investigator# 75104
Brno, Czech Republic, 638 00
Site Reference ID/Investigator# 76788
Prague 2, Czech Republic, 128 50
Site Reference ID/Investigator# 75102
Uherske Hradiste, Czech Republic, 686 01
Site Reference ID/Investigator# 75103
Zlin, Czech Republic, 760 01
Germany
Site Reference ID/Investigator# 78014
Ratingen, Germany, 40882
Puerto Rico
Site Reference ID/Investigator# 75079
Caguas, Puerto Rico, 00725
Site Reference ID/Investigator# 75078
Vega Baja, Puerto Rico, 00693
Romania
Site Reference ID/Investigator# 76787
Bucharest, Romania, 020475
Site Reference ID/Investigator# 75978
Cluj-Napoca, Romania, 400006
Site Reference ID/Investigator# 76433
Ploiesti, Romania, 100337
Slovakia
Site Reference ID/Investigator# 76934
Banska Bystrica, Slovakia, 97405
Site Reference ID/Investigator# 76935
Senica, Slovakia, 905 01
Site Reference ID/Investigator# 76682
Zilina, Slovakia, 010 01
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Andy Payne, PhD AbbVie
  More Information

Additional Information:
No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01712178     History of Changes
Other Study ID Numbers: M13-390, 2012-000535-36
Study First Received: June 14, 2012
Results First Received: May 7, 2014
Last Updated: June 10, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Czech Republic: State Institute for Drug Control
Germany: Paul-Ehrlich-Institut
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Slovakia: State Institute for Drug Control

Keywords provided by AbbVie:
Pharmacodynamic,Pharmacokinetic

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 20, 2014