A phase II, randomized, partially double blind, controlled study to evaluate the immunogenicity, safety, and clinical efficacy of three doses of Neovacs’ TNF-Kinoid in adult patients with rheumatoid arthritis (RA) who have relapsed despite use of an anti-TNFa biological drug, due to anti-drug antibodies
- Conditions
- Rheumatoid arthritisMedDRA version: 12.0Level: PTClassification code 10039073Term: Rheumatoid arthritis
- Registration Number
- EUCTR2009-012041-35-FR
- Lead Sponsor
- eovacs SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 48
Patients will be eligible for entry into the study if they meet the following criteria:
•Diagnosis of Rheumatoid Arthritis (RA) since at least six months prior to first study product administration.
•Patients who the investigator believes are able and willing to comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits).
•A male or female between 18 and 70 years of age at the time of the first immunization.
•Active RA disease as evidenced by a Disease Activity Score 28 (DAS 28) = 3.2
•Current or past treatment with an anti-TNFa antagonist (infliximab, adalimumab)
•A wash-out period of at least two months between the last administration of infliximab, adalimumab or etanercept and the first administration of the study product.
•History of positive response defined as ACR20 or DAS 28 decrease = 1.2 with current or past anti-TNFa antagonist treatment.
•Secondary treatment failure to current or past anti-TNFa antagonist treatment as defined by:
•Investigator opinion. OR
•DAS28 increase = 0.6 during last six months. OR
•Decrease in EUropean League Against Rheumatoid (EULAR) score.
•Positive antibodies against TNFa antagonist (ADA) at screening or on a sample taken since discontinuation of infliximab and/or adalimumab.
•Current treatment with MTX, with stable dosage (maximum 20 mg/week) since at least four weeks (folate supplements are allowed) prior to first study product administration.
•If the patient is female, she must be of non-childbearing potential, i.e., either surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must have used adequate contraceptive precautions (e.g., intrauterine contraceptive device, oral contraceptives, diaphragm or condom in combination with contraceptive jelly, cream or foam) for 30 days prior to immunization, have a negative pregnancy test (serum or urine) and must agree to continue such precautions for two months after completion of the immunization series.
•Written informed consent obtained from the patient.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Patients meeting any of the following criteria will be excluded from participation in the study:
•Treatment with non-biological DMARDs other than MTX within four weeks prior to first study product administration.
•Treatment with TNFa antagonist other than infliximab, adalimumab or etanercept within six months prior to first study product administration.
•Treatment with any rheumatoid arthritis biological therapy other than TNFa antagonists at any time prior to first study product administration.
•Administration of high doses of intra-articular corticosteroids for the treatment of an acute mono-arthritis (e.g. knee) following aspiration of synovial fluid within 3 months prior to first study product administration
•History of documented severe bacterial infection within 28 days prior to screening or between screening and first immunization.
•History of primary resistance or intolerance to any TNFa antagonist.
•History of or current congestive heart failure, controlled or not.
•Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within three months prior to the first immunization (except MTX). For corticosteroids, this will mean prednisone, or equivalent, ? 0.5 mg/kg/day. Inhaled steroids are allowed.
•Known history of tuberculosis (TB).
•Positive Mantoux/Purified Protein Derivative (PPD) test (=5mm induration measured 48 hours after intradermal injection of tuberculin) and/or positive interferon-? (IFN ?) TB diagnostic test (as measured by ELISpot method) and/or suspicion of TB at chest X-rays at screening or within three months prior to first administration of study product.
•Positive for Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) including Hepatitis B surface Antigen (HBsAg) and anti-Hepatitis B core (anti-HBc) antibodies.
•Use of any investigational or non-registered product (drug or vaccine) other than the study product(s) within 30 days preceding the first dose of study product(s), or planned use during the study period.
•Administration of any live vaccine within three months prior to study entry (e.g.oral poliomyelitis vaccine, measles-mumps-rubella vaccine, yellow fever vaccine, rotavirus vaccine, varicella vaccine, zoster vaccine, Bacillus Calmette-Guérin (BCG) vaccine).
•Any confirmed or suspected immunosuppressive or immunodeficient condition.
•Pregnancy or lactation.
•History of malignancy, except cutaneous basal cell carcinoma.
•History of allergic disease or reactions likely to be exacerbated by any component of the study product.
•Current serious neurologic or mental disorders.
•Acute disease at the time of enrolment (acute disease is defined as the presence of a moderate or severe illness with or without fever). The study product can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e. Oral or Axillary temperature <37.5°C.
•Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality as determined by physical examination or laboratory tests, at the discretion of the investigator.
•Abnormal laboratory values, in particular:
•Hemoglobin < 10 g/dl
•White blood cells (WBC) count < 3.0x10-9/L or =15x10-9/L
•Platelet count < 100x10-9/L.
•Serum creatinine level >145µmoles/L.
•Serum Alanine amino transferase (ALT) or Aspartate amino transferase (AST) >2.5ULN.
•Al
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to identify the best dose and schedule of administration of TNF-K in terms of anti-TNFa antibody response induced by two or three injections of TNF-K (Day 0, 28 or Day 0, 7, 28) at three dose levels (90, 180 or 360 mcg).;Primary end point(s): Immune responses<br>•Proportion of patients with at least a 3-fold increase in antibody response to TNFa vs baseline at Day 38. <br>;Secondary Objective: The secondary objectives are:<br>•To characterize the immune response after two or three injections at each dose level until the anti-TNF antibody response declines to baseline level and at least until Month12. <br>•To evaluate the clinical response to immunization with TNF-K.<br>•To assess the safety after two or three injections at each dose level.<br>
- Secondary Outcome Measures
Name Time Method