A Study to Determine the Body's Immune Response To a Vaccination for Herpes Zoster In Subjects Who Have Rheumatoid Arthritis and Receive Tofacitinib (CP-690,550) (the drug being tested) or Placebo

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2014-000706-34-GB
• Date of registration: 18/07/2014
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc. 235 East 42nd Street, New York, NY 10017
• Public title: A Study to Determine the Body's Immune Response To a Vaccination for Herpes Zoster In Subjects Who Have Rheumatoid Arthritis and Receive Tofacitinib (CP-690,550) (the drug being tested) or Placebo
• Scientific title: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 2 STUDY TO ASSESS THE IMMUNE RESPONSE FOLLOWING ADMINISTRATION OF ZOSTER VACCINE TO SUBJECTS WITH RHEUMATOID ARTHRITIS RECEIVING TOFACITINIB (CP-690,550) OR PLACEBO WITH BACKGROUND METHOTREXATE TREATMENT
• Date of first enrolment: 06/10/2014
• Target sample size: 140
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000706-34
• 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: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Germany, Hungary, 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. Must be at least 50 years of age or older.
3. Has moderate to severe rheumatoid arthritis inadequately controlled with methotrexate alone at the screening visit as documented by the following:
a. Score of 6 or greater on the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Rheumatoid Arthritis.
b. Has =4 tender/painful joints on motion and =4 swollen joints (28 joint count) at screening.
c. Screening C-reactive protein (CRP) >3 mg/L in the central laboratory.
4. Meets Class I, II or III of the American College of Rheumatology (ACR) 1991 Revised Criteria for Global Functional Status in RA where usual self-care activities including dressing, feeding, bathing, grooming, and toileting; avocational (recreational and/or leisure) and vocational (work, school, homemaking) activities are subject-desired and age and sex-specific.
a. Class I – Completely able to perform usual activities of daily living (self-care, vocational, and avocational).
b. Class II – Able to perform usual self-care and vocational activities, but limited in avocational activities.
c. Class III – Able to perform usual self-care activities, but limited in vocational and avocational activities.
5. Has taken methotrexate continuously for at least 4 months prior to the Screening visit and has taken a stable weekly dose of methotrexate with supplemental folic or folinic acid for at least 6 weeks prior to the Visit 2/Day 1 visit. (Conversion from parenteral to oral will require “stabilization” over this period of time as well).
a. Methotrexate doses less than 15 mg/week are allowed only if there is documented intolerance or toxicity from higher doses.
b. Doses higher than 25 mg/week are not permitted under any circumstances.
c. Doses higher than 20 mg/week are not permitted under any circumstances in subjects who weigh <140 lbs or 63 kg.
d. Folic acid doses should be at least 5 mg per week; folinic acid doses should be at least 2.5 mg per week.
e. The subject must have an inadequate clinical response to methotrexate defined as the presence of sufficient residual disease activity to meet the entry criteria.
6. Female subjects of childbearing potential must test negative for pregnancy.
7. Male and female subjects of childbearing potential must agree to use two highly effective methods of contraception throughout the study and for at least 3 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.
8. Female subjects who are not of childbearing potential must meet at least one of the following criteria:
• Have undergone a documented hysterectomy and/or bilateral oophorectomy;
• Have medically confirmed ovarian failure or;
• Achieved post menopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle-stimulation hormone (FSH) level within the laboratory’s reference range for postmenopausal females.
9. Subjects must screen negative for active tuberculosis or inadequately treated tuberculosis (TB) infection (active or latent) as evidenced by the following (see protoc
Exclusion criteria:
1. Subjects who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees directly involved in the conduct of the trial.
2. Subjects who have an allergy or hypersensitivity to MTX, subjects who have experienced a serious toxicity when administered MTX, or have any contraindication to treatment with MTX according to the local label for treatment of RA with MTX.
3. Pregnant females; breastfeeding females; males and females of childbearing potential who are unwilling or unable to use two (2) highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 3 months after last dose of investigational product.
4. Subjects with infections or history of infections:
a. Any infection requiring treatment within 2 weeks prior to Visit 2/Day 1.
b. Any infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged to be an opportunistic infection or clinically significant by the investigator, within the past 6 months.
c. Infected joint prosthesis at any time with the prosthesis still in situ.
d. Recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
e. Subjects will be screened for human immunodeficiency virus (HIV). Subjects who test positive for HIV will be excluded from the study.
f. Subjects will be screened for hepatitis B virus infection and will be excluded if positive for hepatitis B surface antigen (HBsAg). Subjects with HBsAg negative testing but who test positive for hepatitis B core antibody (HBcAb) must have further testing for hepatitis B surface antibody (HBsAb). If HBsAb is negative, the subject will be excluded from the study.
g. Subjects will be screened for hepatitis C virus antibodies (HCV Ab). Subjects with positive HCV Ab tests will be reflex tested for hepatitis C virus ribonucleic acid (HCV RNA). Only subjects with negative HCV Ab or negative HCV RNA will be allowed to enroll in the study.
h. Subjects are excluded for current active tuberculosis infection or prior active or latent tuberculosis that was inadequately treated or cannot be documented (See Inclusion Criteria #9).
5. Subjects with any current malignancy or a history of malignancy, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
6. Subjects with any uncontrolled clinically significant laboratory abnormality or any of the following laboratory abnormalities:
a. Evidence of hematopoietic disorder or hemoglobin <10 g/dL;
b. Absolute lymphocyte count <0.75 x 1 000 000 000/L (<750/mm3);
c. Absolute neutrophil count <1.2 x 1 000 000 000/L (<1000/mm3);
d. Platelet count <100 x 1 000 000 000/L (<100,000/mm3);
e. Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) >1.5 times the upper limit of normal (x ULN);
f. Estimated glomerular filtration rate (GFR) <40 mL/min using the Cockcroft-Gault formula.
7. Participation in other studies involving investigational drug(s) (Phases 1-4) within 4 weeks or 5 half-lives (whichever is longer) after discontinuation of the investigational compound before the current study begins and/or during study participation, unless further restrictions to class of compound are specified in

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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

RHEUMATOID ARTHRITIS
MedDRA version: 17.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: tofacitinib citrate
Product Code: CP-690,550 – 10
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: tofacitinib
CAS Number: 540737-29-9
Other descriptive name: TOFACITINIB CITRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): 1. Fold increase from vaccination baseline in VZV antibodies as measured by an enzyme-linked immunosorbent assay (ELISA) for VZV immunoglobulin G (IgG) at 6 weeks post-vaccination (Week 4 on study treatment).

Timepoint(s) of evaluation of this end point: Week 4 on study treatment (6 weeks post-vaccination)

Secondary Objective: 1. To further evaluate the effect of tofacitinib on VZV-specific cell mediated immunity and additional antibody response assessments to zoster vaccine by evaluating the percentage of subjects who respond and the magnitude of the immune response.
2. To evaluate the safety and tolerability of a regimen where zoster vaccine is administered at least 2 weeks prior to initiation of treatment with tofacitinib with background methotrexate.

Main Objective: To evaluate the effect of tofacitinib on varicella-zoster virus (VZV)-specific immunoglobulin responses in subjects with RA on background methotrexate therapy.

Secondary Outcome(s)

Secondary end point(s): 1. VZV-specific cell mediated immunity (CMI) to zoster vaccine as measured by interferon (IFN)-y enzyme-linked immunosorbent spot (ELISPOT):
a. Absolute number of spot-forming cells/1 000 000 peripheral blood mononuclear cells (PBMCs) at baseline and 2, 6 and 14 weeks following immunization (Study Day 1, Week 4 and Week 12).
b. Occurrence of a =1.5-fold increase from vaccination baseline in spot-forming cells/1 000 000 PBMCs at 2, 6 and 14 weeks following immunization (Study Day 1, Week 4 and Week 12).
c. Fold increase from vaccination baseline in spot-forming cells/1 000 000 PBMCs at 2, 6 and 14 weeks following immunization (Study Day 1, Week 4 and Week 12).
2. VZV antibodies as measured by ELISA for VZV IgG:
a. VZV-specific IgG levels at 2 weeks, 6 weeks and 14 weeks (Study Day 1, Week 4 and Week 12) following immunization.
b. Occurrence of a =1.5-fold increase from vaccination baseline in VZV-specific IgG levels at 2, 6 and 14 weeks following immunization (Study Day 1, Week 4 and Week 12).
c. Fold increase from vaccination baseline in VZV-specific IgG levels at 2 and 14 weeks following immunization (Study Day 1 and Week 12).

Timepoint(s) of evaluation of this end point: Timepoints are all listed in the list of secondary endpoints.

Secondary ID(s)

70,903

A3921237

Source(s) of Monetary Support

Pfizer Inc., 235 East 42nd Street, New York, NY 10017