RANDOMIZED STUDY OF PF-06438179 AND INFLIXIMAB IN COMBINATION WITH METHOTREXATE IN SUBJECTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS

• Register: EUCTR
• Last refreshed on: 3 July 2017
• Main ID: EUCTR2013-004148-49-FR
• Date of registration: 18/06/2015
• Prospective Registration: No
• 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: 23/02/2015
• 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
• Affiliation: Pfizer Inc.

• Name: Clinical Trials.gov Call Center
• 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 (at least 1 mg/day on =5 days/week) or folinic acid (=5 mg once per week) supplementation for at least 21 days prior to the first dose of study drug.
10. No current or prior treatment with infliximab or lymphocyte depleting therapies (eg, Rituximab, Campath).
11. Subjects may have received up to 2 doses of one biologic therapy for RA, including anti-TNF therapies (other than infliximab), anakinra, or abatacept, if enrolling after a washout period of at least 3 months or 5 half lives prior to the first dose of st
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 as outlined in this protocol for the duration of the study and 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 as defined by the following lab criteria:
a. Hemoglobin (Hgb) <9 g/dL.
b. Absolute neutrophil count (ANC) = 1500 cells/mm^3.
c. White blood cell count <3.0 x 10^9/L.
d. Platelets <100 x 10^9/L.
e. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =2 times the upper limit of normal.
f. Bilirubin =1.5 times the upper limit of normal.
g. Serum creatinine =1.5 mg/dL.
Subjects who do not meet a lab entry criteria but satisfy all other study entry criteria may have the lab re-tested within 14 days and, if within the required range, will be eligible to enroll into the study provided all other inclusion/exclusion criteria are met.
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 (including
multiple sclerosis, optic neuritis, Guillain-Barré syndrome).
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 (eg, Epstein Barr Virus (EBV) related lymphoproliferative disorder, lymphoma, leukemia).
8. History of disseminated or recurrent infection of herpes simplex, EBV, human papilloma virus (HPV), or varicella zoster. A 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)
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 the following DMARDs within the relevant
washout period.
15. Known requirement for treatment with prohibited concomitant medications during study.
16. Significant trauma or surgical procedure within 4 weeks prior to first dose of study
drug.
17. Known or Screen test positive human immunodeficiency virus (HIV), hepatitis B
virus,

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Rheumatoid Arthritis
MedDRA version: 18.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

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)

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 and PK/PD relationship in response to infliximab-Pfizer and infliximab-EU.
- To evaluate the individual ACR parameters of clinical response to infliximab-Pfizer and infliximab-EU.

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.

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.