Study of Etanercept in Subjects With Rheumatoid Arthritis Who Have Had an Inadequate Response to Adalimumab or Infliximab Plus Methotrexate (SERUM)

This study is currently recruiting participants.
Verified April 2014 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01783015
First received: January 31, 2013
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

The first 12 weeks of this study will compare the efficacy of etanercept 50 mg once-weekly to placebo in subjects with rheumatoid arthritis who have not responded well to infliximab or adalimumab plus methotrexate. This comparison will be performed for all subjects and separately for subjects who are anti-drug antibody positive for one of these medications. From week 12 to week 24, all subjects will receive etanercept 50 mg once-weekly. The effect of anti-drug antibody status on the efficacy of etanercept as well as the safety profile of etanercept in these subjects will also be evaluated throughout the study.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Etanercept
Drug: Etnaercept
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of Etanercept in Subjects With Rheumatoid Arthritis Who Have Had an Inadequate Response to Adalimumab or Infliximab Plus Methotrexate

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change from Baseline in Disease Activity Score Based on 28-joints Count (DAS28) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the c-reactive protein (CRP) and Subject's General Health VAS assessment(participant rated health assessment with scores ranging 0 to 100; higher scores indicate worse health status).


Secondary Outcome Measures:
  • Change from Baseline in Disease Activity Score Based on 28-joints Count (DAS28) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the c-reactive protein (CRP) and ubject General Health as measured on a 0 to 100 mm Visual Analog Scale (VAS), with 0 mm = very well and 100 mm = extremely bad

  • Number of Participants with DAS28 <3.2 [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
    DAS28 <3.2 = low disease activity

  • Number of Participants with DAS28 <2.6 [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
    DAS28 <2.6 = remission

  • Number of Participants Acheiving American College of Rheumatology 20% (ACR20) Response [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
    ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of the 5 remaining ACR core measures: 1) physician's global assessment of disease activity, 2) subject's global assessment, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire (HAQ), and 5) C-reactive protein (CRP)

  • Number of Participants Achieving American College of Rheumatology 50% (ACR50) Response [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
    ACR50 response: greater than or equal to (≥) 50 percent (%) improvement in tender or swollen joint counts and ≥ 50% improvement in 3 of the 5 remaining ACR core measures: 1) physician's global assessment of disease activity, 2) subject's global assessment, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire (HAQ), and 5) C-reactive protein (CRP)

  • Number of Participants Achieving American College of Rheumatology 70% (ACR70) Response [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
    ACR70 response: greater than or equal to (≥) 70 percent (%) improvement in tender or swollen joint counts and ≥ 70% improvement in 3 of the 5 remaining ACR core measures: 1) physician's global assessment of disease activity, 2) subject's global assessment, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire (HAQ), and 5) C-reactive protein (CRP)

  • Number of Participants Achieving American College of Rheumatology 90% (ACR90) Response [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
    ACR90 response: greater than or equal to (≥) 90 percent (%) improvement in tender or swollen joint counts and ≥ 90% improvement in 3 of the 5 remaining ACR core measures: 1) physician's global assessment of disease activity, 2) subject's global assessment, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire (HAQ), and 5) C-reactive protein (CRP)

  • Number of Participants Acheiving European League against Rheumatism (EULAR) Good and/or Moderate Response [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Number of Participants Acheiving Low Disease Activity or Remission Based on Clinical Disease Activity Index (CDAI) [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Number of Participants Acheiving Low Disease Activity or Remission Based on Simplified Disease Activity Index (SDAI) [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in Clinical Disease Activity Index (CDAI) [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in Simplified Disease Activity Index (SDAI) [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in Number of Tender/Painful Joints [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
    Number of Tender/Painful Joints using the 28 joint count

  • Change from Baseline in Number of Swollen Joints [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
    Number of Swollen Joints using the 28 joint count

  • Change from Baseline in Physician Global Assessment (PGA) of Disease Activity [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
    Physician Global Assessment of Disease Activity a 0 to 10 scale, with 0 = no disease activity.

  • Change from Baseline in Subject Global Assessment of Disease Activity [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
    Subject Global Assessment of Disease Activity as measured on a 0 to 10 scale, with 0 = no disease activity.

  • Change from Baseline in Subject General Health [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
    Subject General Health as measured on a 0 to 100 mm Visual Analog Scale (VAS), with 0 mm = very well and 100 mm = extremely bad.

  • Change from Baseline in Subject Pain [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
    Subject Pain as measured on a 0 to 100 mm Visual Analog Scale (VAS), with 0 mm = no pain and 100 mm = most severe pain.

  • Change from Baseline in C-Reactive Protein (CRP) [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
    The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

  • Change from Baseline in Health Assessment Questionnaire Disability and Discomfort Scales (HAQ-DI) [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in Euro Qol EQ-5 Dimensions Questionnaire (EQ-5D) [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in Short Form-36 Health Survey (SF-36) [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in Patient Acceptable Symptom State (PASS) [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in Vectra disease activity (DA) levels [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Number of Participants with Positive Etanercept Anti-drug Antibody Status [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Number of Participants with Positive Etanercept Neutralizing Anti-drug Antibody Status [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: September 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Subjects who are mAb ADA positive
Drug: Etanercept
Etanercept 50 mg once-weekly
Experimental: Group B
Subjects who are mAb ADA negative
Drug: Etnaercept
Etanercept 50 mg once-weekly
Placebo Comparator: Group C
Subjects who are mAb ADA positive
Drug: Placebo
Etanercept placebo once-weekly
Placebo Comparator: Group D
Subjects who are mAb ADA negative
Drug: Placebo
Etanercept placebo once-weekly

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Met the 1987 ACR Revised Criteria for RA
  2. A history of inadequate response to infliximab or adalimumab in combination with methotrexate.
  3. A stable dose of oral methotrexate for at least 6 weeks before the baseline visit.

Exclusion Criteria:

  1. ACR functional class IV
  2. Prior treatment with etanercept; both infliximab and adalimumab; or any immunosuppressive biologic agent other than infliximab or adalimumab.
  3. Discontinuation of infliximab or adalimumab for a primary reason other than inadequate efficacy response.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01783015

Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021

Locations
Australia, Victoria
Private Rooms of Dr Anthony Boers Not yet recruiting
Morwell, Victoria, Australia, 3840
Australia, Western Australia
RK Will Pty Ltd Recruiting
Victoria Park, Western Australia, Australia, 6100
Belgium
Cliniques Universitaires Saint-Luc / Service de Rhumatologie Recruiting
Bruxelles, Belgium, 1200
Cliniques Universitares-Mont Godinne Recruiting
Yvoir, Belgium, 5530
France
CHU Lapeyronie Recruiting
Montpellier, France, 34000
Hong Kong
Tseung Kwan O Hospital Recruiting
Tseung Kwan O, New Territories, Hong Kong
Queen Mary Hospital Recruiting
Hong Kong, Hong Kong
Tuen Mun Hospital Recruiting
Tuen Mun, NT, Hong Kong
Pok Oi Hospital Recruiting
Yuen Long, NT, Hong Kong
Israel
Bnai Zion Medical Ctr Recruiting
Haifa, Israel, 31048
Meir Medical Center Recruiting
Kfar Saba, Israel, 44281
Department of Rheumatology Recruiting
Tel Aviv, Israel, 64239
Netherlands
Reade (Jan Van Breemen Instituut (JBI)) Recruiting
Amsterdam, Noord Holland, Netherlands, 1056 AB
Russian Federation
LLC Research Medical Complex Your Health Recruiting
Kazan, Tatarstan, Respublika, Russian Federation, 420097
LLC "Alliance Biomedical-Russian Group" Recruiting
Izhevsk, Russian Federation, 426064
GOU VPO Krasnoyarsk State Med Univ Recruiting
Krasnoyarsk, Russian Federation, 660022
GOU VPO Moscow SU of Medicine & Dentistry ba Recruiting
Moscow, Russian Federation, 127473
City Clinical Hospital #40 Recruiting
Moscow, Russian Federation, 129301
Scientific Institute of Rheumatology of Russian Academy of Medical Science Recruiting
Moscow, Russian Federation, 115522
FSBI Scientific and Research Institution of Recruiting
Novosibirsk, Russian Federation, 630117
Spain
Hospital de Basurto Recruiting
Bilbao, Vizcaya, Spain, 48013
Xerencia de Xestión Integrada A Coruña, Hospital Universitario A Coruña Recruiting
A Coruña, Spain, 15006
Hospital de la Santa Creu i San Pau Recruiting
Barcelona, Spain, 08025
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Hospital General Universitario Gregorio Maranon Recruiting
Madrid, Spain, 28007
H.G.U. G. Marañón Recruiting
Madrid, Spain, 28007
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Hospital Regional Universitario Carlos Haya. Hospital Civil. Recruiting
Málaga, Spain, 29009
H.U.V. Macarena Recruiting
Sevilla, Spain, 41009
Hospital Infanta Luisa Recruiting
Sevilla, Spain, 41010
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01783015     History of Changes
Other Study ID Numbers: B1801355
Study First Received: January 31, 2013
Last Updated: April 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Rheumatoid arthritis
etanercept
methotrexate
infliximab
adalimumab
anti-drug antibody

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Infliximab
TNFR-Fc fusion protein
Adalimumab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal

ClinicalTrials.gov processed this record on April 15, 2014