A phase II, randomized, double-blind, controlled study to evaluate the immune responses, safety and clinical efficacy of three doses of Neovacs’ TNF-Kinoid in adult patients with rheumatoid arthritis who have relapsed despite anti-TNFa biological therapy

• Conditions: Rheumatoid arthritis; MedDRA version: 14.1Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2009-012041-35-BE
• Lead Sponsor: eovacs SA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09-30
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

Patients will be eligible for entry into the study if they meet the following criteria:
1.Diagnosis of RA according to the revised 1987 criteria of the American College of Rheumatology (ACR) (Arnett 1988) since at least six months prior to first study product administration.
2.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).
3.A male or female between 18 and 70 years of age at the time of the first immunization.
4.Active RA disease as evidenced by a Disease Activity Score 28 (DAS 28) = 3.2.
5.History of treatment with TNFa antagonist (infliximab, adalimumab, etanercept, certolizumab, golimumab).
6.A wash-out period before the first administration of the study product of:
•at least ten weeks since the last administration of certolizumab or golimumab
•at least eight weeks since the last administration of infliximab
•at least four weeks since the last administration of adalimumab or etanercept
7.History of positive response defined as an ACR20 or a DAS 28 decrease = 1.2 or by the investigator opinion with previous TNFa antagonist treatment.
8.Secondary treatment failure to maximum one previous TNFa antagonist treatment as defined by:
•Investigator opinion.
OR
•DAS28 increase = 0.6 during the last six months.
OR
•Decrease in European League Against Rheumatoid (EULAR) score.
9.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) and must agree to continue such precautions during the whole study period .
10.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

Exclusion Criteria

Patients meeting any of the following criteria will be excluded from participation in the study:
1.Treatment with non-biological DMARDs within four weeks prior to first study product administration. MTX is allowed provided it is administered at a stable dosage = 20mg/week since at least 4 weeks.
2.Treatment with any rheumatoid arthritis biological therapy other than TNFa antagonists at any time prior to first study product administration.
3.Administration of high doses of intra-articular corticosteroids for the treatment of an acute mono-arthritis (e.g. knee) within 3 months prior to first study product administration. High dose of corticosteroids is defined as >50 mg triamcinolone or equivalent)
4.History of documented severe bacterial infection within 28 days prior to first immunization.
5.History of primary resistance or intolerance to any TNFa antagonist.
6.History of or current congestive heart failure, controlled or not.
7.Corticosteroids (prednisone, or equivalent, =10 mg per day) are allowed if they are administered at stable dosage since at least 4 weeks prior to the first immunization. Inhaled and topical steroids are allowed.
8.Known history of tuberculosis (TB).
9.Suspicion of TB at chest X-rays at screening or within three months prior to first administration of study product.
10.Suspicion of latent or active tuberculosis as defined by:
•Positive Mantoux/Purified Protein Derivative (PPD) test (=5mm induration measured 48 to 72 hours after intradermal injection of tuberculin) at screening or within one year prior to first administration of study product.
•and/or positive interferon-? (IFN ?) TB diagnostic test (as measured by the ELISpot method) at screening or within 30 days prior to first administration of study product.
11.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.
12.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.
13.Administration of any live vaccine within three months prior to first administration of study product (e.g. oral poliomyelitis vaccine, measles-mumps-rubella vaccine, yellow fever vaccine, rotavirus vaccine, varicella vaccine, zoster vaccine, Bacillus Calmette-Guérin (BCG) vaccine, oral typhoid vaccine).
14.Any confirmed or suspected immunosuppressive or immunodeficient condition.
15.Pregnancy, lactation or planned pregnancy during the study.
16.History of malignancy, except surgically treated cutaneous basal cell carcinoma
17.History of allergic disease or reactions likely to be exacerbated by any component of the study product, including seafood allergy
18.Current serious neurologic or mental disorders.
19.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.
20.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.
21.Abn

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified