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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 21 August 2017
Main ID:  EUCTR2013-004148-49-PL
Date of registration: 27/08/2014
Prospective Registration: Yes
Primary sponsor: Pfizer Inc.
Public title: RANDOMIZED STUDY OF PF-06438179 AND INFLIXIMAB IN COMBINATION WITH METHOTREXATE IN SUBJECTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS
Scientific title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND STUDY ASSESSING THE EFFICACY AND SAFETY OF PF-06438179 AND INFLIXIMAB IN COMBINATION WITH METHOTREXATE IN SUBJECTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS WHO HAVE HAD AN INADEQUATE RESPONSE TO METHOTREXATE
Date of first enrolment: 21/10/2014
Target sample size: 614
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004148-49
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Argentina Australia Bosnia and Herzegovina Brazil Bulgaria Canada Colombia Czech Republic
European Union France Georgia Germany Guatemala Hungary Israel Japan
Korea, Republic of Lithuania Mexico Morocco Peru Philippines Poland Russian Federation
Serbia South Africa Tunisia Ukraine United Kingdom United States
Contacts
Name: Clinical Trials.gov Call Center   
Address:  235 E 42nd Street NY 10017 New York United States
Telephone: +18007181021
Email: ClinicalTrials.gov_Inquiries@pfizer.com
Affiliation:  Pfizer Inc.
Name: Clinical Trials.gov Call Center   
Address:  235 E 42nd Street NY 10017 New York United States
Telephone: +18007181021
Email: ClinicalTrials.gov_Inquiries@pfizer.com
Affiliation:  Pfizer Inc.
Key inclusion & exclusion criteria
Inclusion criteria:
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Male and female subjects aged 18 years or older at the time of informed consent. Where required by regulations, consent from a legal representative is required for all subjects who are younger than 20 years of age.
4. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 6 months after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
Female subjects who are not of childbearing potential must meet at least 1 of the following criteria:
a. Achieved postmenopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum FSH level in the laboratory’s reference range for postmenopausal females.
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy.
c. Have medically confirmed ovarian failure.
All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy or bilateral oophorectomy) will be considered to be of childbearing potential.
5. Diagnosis of rheumatoid arthritis (RA) based on 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR)
classification criteria (see Appendix 1) for RA for at least a 4 month duration.
6. Meets Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA (see Appendix 2).
7. Moderately to severely active RA disease as defined by the following criteria:
a. = 6 tender joints (of 68 assessed) at both Screening and Baseline, and
b. = 6 swollen joints (of 66 assessed) at both Screening and Baseline, and
c. Hs-CRP =10 mg/L (=1 mg/dL) at Screening, performed by a central
laboratory. Subjects who do not meet this entry criteria but satisfy all other study entry criteria may have serum hs-CRP concentration re-tested once within 14 days and, if the repeat hs-CRP concentration is =10 mg/L
(=1 mg/dL), will be eligible to enroll into the study provided all other
inclusion/exclusion criteria are met.
8. Stable dose of oral or parenteral methotrexate of 10 to 25 mg/week. Subjects who cannot tolerate 10 to 25 mg/week methotrexate may take a lower dose of as low as 7.5 mg/week (as low as 6 mg/week in geographic regions where specified by local guidance). Subjects must have received methotrexate for at least 12 weeks and be on a stable dose for at least 4 weeks prior to first dose of study drug.
9. Stable dose of oral folic (=5 mg once per week)
10. If receiving an oral corticosteroid, subjects must be on a stable dose of
= 10 mg/day of prednisone (or equivalent) for 4 weeks prior to the first dose of study drug, without any intramuscular (IM) or intra-articular (IA) corticosteroids within the 4 weeks prior to the first dose of study drug.
11. If receiving a NSAID/Cox-2 inhibitor, subject must be on a stable dose of only one NSAID/Cox-2 inhibitor drug for 4 weeks prior to the first dose of study drug at a dosage less than or equal to the maximum recom

Exclusion criteria:
1. Pregnant females and breastfeeding females; males and females of
childbearing potential who are unwilling or unable to use a highly
effective method of contraception for the duration of the study and for at
least 6 months after last dose of investigational product. Females must
not breastfeed for at least 6 months after last dose of investigational
product.
2. Clinically significant laboratory abnormalities at Screening, including
but not limited to inadequate bone marrow, liver, renal and immune
system functions.
3. Evidence or history of moderate or severe heart failure (NYHA class
III/IV, see Appendix 11 for NYHA classification of congestive heart
failure) and subjects who are contraindicated for treatment with
infliximab in accordance with the approved local label.
4. Evidence of current or recent history of uncontrolled, clinically
significant infectious, hematological, renal, endocrine, pulmonary,
gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or
allergic disease.
5. Evidence or history of seizures, or nervous system demyelinating
diseases.
6. Evidence or history of a malignancy within the past 5 years with the
exception of adequately treated or excised non-metastatic basal cell or
squamous cell cancer of the skin, or cervical carcinoma in situ with no
evidence of recurrence.
7. History of any lymphoproliferative disorder.
8. History of recurrent (more than one episode) limited herpes zoster or
disseminated (a single episode) herpes zoster or herpes simplex. History
of disseminated or recurrent infection of EBV or human papilloma virus
(HPV) (single, limited episode in the past is not exclusionary)
9. Infection requiring hospitalization or parenteral antimicrobial therapy
judged clinically significant by the investigator within 6 months prior to
first dose of study drug.
10. History of an infected joint prosthesis at any time.
11. History of recurrent inflammatory joint disease other than RA (eg,
post infectious arthritis, gout, etc.) or history of any other autoimmune
rheumatic diseases (eg, vasculopathies, spondyloarthropathies, etc.)
other than Sjogren's syndrome.
12. Evidence of untreated or inadequately treated latent, or inadequately
treated or active infection with tuberculosis (TB). Subjects currently
receiving treatment for active or latent TB are excluded.
13. Chest radiography with evidence of active TB, fungal infections, or
other clinically significant abnormalities taken at Screening or within 12
weeks prior to first dose of study drug on Day 1.
14. Any current or prior treatment for DMARDs within the relevant
washout period.
15. Current or prior treatment with infliximab or lymphocyte depleting
therapies (eg, Rituximab, Campath). Prior exposure to biologic therapy
for RA (with the exception of up to 2 doses of one biologic therapy for
RA, including anti-TNF therapies(other than infliximab). For prior
exposure to a biologic therapy for RA, a washout period of at least 12
weeks or 5 half lives(whichever is longer) is required prior to the first
dose of study drug.
16. Known requirement for treatment with prohibited concomitant
medications during study.
17. Significant trauma or surgical procedure within 4 weeks prior to first
dose of study drug.
18. Known or Screen test positive human immunodeficiency virus (HIV),
hepatitis B virus (HBV), or hepatitis C virus (HCV).
19. Screening 12-lead ECG that demonstrates clinically relevant
abnormalities which
may affect subject safety or interpretation o


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Rheumatoid Arthritis
MedDRA version: 19.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
Intervention(s)

Product Name: Infliximab-Pfizer
Product Code: PF-06438179
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Current Sponsor code: PF-06438179
Other descriptive name: Infliximab-Pfizer
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Remicade
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Other descriptive name: Infliximab-EU
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)
Main Objective: To compare the efficacy between infliximab-Pfizer and infliximab-EU in subjects with moderately to severely active RA who are treated with infliximab in combination with methotrexate.
Primary end point(s): ACR20 response (= 20% improvement by ACR criteria) at Week 14.
Secondary Objective: - To evaluate the overall safety and tolerability of infliximab-Pfizer and infliximab-EU.
- To evaluate the immunogenicity of infliximab-Pfizer and infliximab-EU.
- To evaluate the overall safety, tolerability and immunogenicity of infliximab-Pfizer after treatment transition from infliximab-EU to infliximab-Pfizer.
- To evaluate the population pharmacokinetics (PK) of infliximab-Pfizer and infliximab-EU.
- To evaluate the pharmacodynamic (PD) response to infliximab-Pfizer and infliximab-EU.
- To evaluate the individual ACR parameters of clinical response to infliximab-Pfizer and infliximab-EU.
Timepoint(s) of evaluation of this end point: At week 14. In addition, point estimates and 95% CIs in difference of
ACR20 response rates between the two treatment arms at Weeks 2, 4, 6, 12, 22, and 30, will be used to support the primary efficacy analysis.
Secondary Outcome(s)
Secondary end point(s): - Categorical and continuous measures of clinical efficacy, including ACR20 (other than Week 14), ACR50, ACR70, change in DAS28-CRP (Disease Activity Score-28 4 components based on CRP), DAS remission (=2.6), EULAR (European League Against Rheumatism) response, ACR/EULAR remission, and change in HAQ-DI.
- Safety measures characterized by type, incidence, severity, timing, seriousness and relatedness of adverse events and laboratory abnormalities.
- Change from baseline in individual components of ACR response.
- Incidence and titers of anti-drug antibodies (ADA) and neutralizing antibodies (Nab) in response to infliximab-Pfizer and infliximab-EU.
- Serum drug concentrations.
Timepoint(s) of evaluation of this end point: At Week 14 and other protocol-defined time points up to Week 30.
Secondary ID(s)
2013-004148-49-LT
B5371002
Source(s) of Monetary Support
Pfizer Inc.
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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