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    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2014-000706-34
    Sponsor's Protocol Code Number:A3921237
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-07-18
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2014-000706-34
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    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
    A.4.1Sponsor's protocol code numberA3921237
    A.5.4Other Identifiers
    Name:US IND NumberNumber:70,903
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorPfizer Inc. 235 East 42nd Street, New York, NY 10017
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportPfizer Inc., 235 East 42nd Street, New York, NY 10017
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPfizer Inc.
    B.5.2Functional name of contact pointClinical Trials.gov Call Center
    B.5.3 Address:
    B.5.3.1Street Address235 East 42nd Street
    B.5.3.2Town/ cityNew York
    B.5.3.3Post codeNY 10017
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1 800 718 1021
    B.5.5Fax number+1303739 1119
    B.5.6E-mailclinicaltrials.govCallCenter@pfizer.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nametofacitinib citrate
    D.3.2Product code CP-690,550 – 10
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNtofacitinib
    D.3.9.1CAS number 540737-29-9
    D.3.9.3Other descriptive nameTOFACITINIB CITRATE
    D.3.9.4EV Substance CodeSUB33105
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    RHEUMATOID ARTHRITIS
    E.1.1.1Medical condition in easily understood language
    RHEUMATOID ARTHRITIS
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10039073
    E.1.2Term Rheumatoid arthritis
    E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the effect of tofacitinib on varicella-zoster virus (VZV)-specific immunoglobulin responses in subjects with RA on background methotrexate therapy.
    E.2.2Secondary objectives of the trial
    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.
    E.2.3Trial contains a sub-study No
    E.3Principal 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 protocol)
    10. Subjects must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
    E.4Principal 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 Protocol Section 4.2 and 5.6.
    8. Subjects requiring or having received any prohibited concomitant medication or dietary supplement as outlined in the protocol, including:
    a. Subjects who have received any vaccines within 6 weeks prior to the first dose of study drug or at any time during treatment or within 6 weeks following discontinuation of study drug, except for the zoster vaccine which will be administered as per protocol.
    b. Subjects who have been previously treated with tofacitinib.
    c. Subjects who are being treated with biologic or non-biologic DMARDs (including antimalarials) other than MTX within their specified washout window at study entry.
    d. Subjects who are being treated with corticosteroids, other than low dose oral corticosteroids in doses equivalent to <=10 mg prednisone per day at study entry. Subjects who are already on oral corticosteroids must be on a stable dose of <=10 mg/day of prednisone or equivalent for 4 weeks prior to first dose of study drug.
    e. No intraarticular, intramuscular, or intravenous corticosteroids administered within 4 weeks prior to the first dose of study drug.
    f. Subjects who require concomitant treatment with medications that are potent inhibitors of cytochrome P450 3A4 (CYP3A4), both moderate inhibitors of CYP3A4 and potent inhibitors of CYP2C19, and potent CYP inducers.

    For the full list of Exclusion Criteria refer to the protocol.
    E.5 End points
    E.5.1Primary 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).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 4 on study treatment (6 weeks post-vaccination)
    E.5.2Secondary 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).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Timepoints are all listed in the list of secondary endpoints.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA7
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Germany
    Hungary
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    End of Trial in a Member State of the EU is defined as the time at which it is deemed that sufficient subjects have been recruited and completed the study as stated in the regulatory application (ie, CTA) and ethics application in the Member State. Poor recruitment (recruiting less than the anticipated number in the CTA) by a Member State is not a reason for premature termination but is considered a normal conclusion to the study in that Member State.
    For further information see the protocol.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days14
    E.8.9.2In all countries concerned by the trial months5
    E.8.9.2In all countries concerned by the trial days14
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 70
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 70
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state14
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 49
    F.4.2.2In the whole clinical trial 140
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Subjects will be offered participation in the long-term trial if study A3921024 is being conducted at the site, or a nearby site, and if the subject is eligible for enrollment.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-09-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-10-06
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-07-06
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