A clinical study to test the efficacy of a new product (TNF-Kinoid) in patients with Rheumatoid Arthritis in whom treatment with methotrexate is not working anymore

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2013-001999-38-PL
• Date of registration: 11/10/2013
• Prospective Registration: Yes
• Primary sponsor: Neovacs SA
• Public title: A clinical study to test the efficacy of a new product (TNF-Kinoid) in patients with Rheumatoid Arthritis in whom treatment with methotrexate is not working anymore
• Scientific title: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Clinical Efficacy of Neovacs’ TNF-Kinoid in Adult Subjects with Active Rheumatoid Arthritis despite Methotrexate Therapy - Phase II study of TNF-K in Rheumatoid Arthritis
• Date of first enrolment: 17/11/2013
• Target sample size: 140
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001999-38
• 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

Belgium, Czech Republic, Georgia, Hungary, Lebanon, Macedonia, the former Yugoslav Republic of, Moldova, Republic of, Poland, Russian Federation, Serbia, Ukraine

Contacts

• Name: Chief Medical Officer
• Affiliation: Neovacs SA

• Name: Chief Medical Officer
• Affiliation: Neovacs SA

Key inclusion & exclusion criteria

Inclusion criteria:
A patient who meets all of the following criteria will be eligible to participate in this study:
1.Be a male or female of between 18 and 75 years of age at the time of randomization.
2.Has had a diagnosis of RA according to the revised ACR criteria (Aletaha et al., 2010) for at least 6 months.
3.Has been treated with and tolerated MTX at a dose of at least 10 mg/week for at least 3 months prior to the first administration of study product, with a MTX dose of = 10 mg/week and =20 mg/week that has been stable for at least 4 weeks prior to first administration of study product. (Note: patients who weigh = 40 kg will be allowed a minimum MTX dose of 7.5 mg/week.)
4.Has at least four swollen joints/66 and/or four tender joints/68, at screening and baseline (SD1).
5.Has CRP=10mg/L at screening. Note: patients may be retested in 7–14 days only if their initial screening value is < 10 mg/L but = 8mg/L.
6.Is positive for rheumatoid factor (RF) or anti-cyclic citrullinated peptides (CCP) antibodies at screening.
7.If using NSAIDs or other analgesics for RA, the patient must have been on stable dose for at least 2 weeks prior to first administration of study product.
8.If using hydroxychloroquine for RA, the patient must have been on stable dose for at least 12 weeks prior to first administration of study product.
9.If using oral corticosteroids, the patient must have been on stable dose equivalent to =10 mg of prednisone/day for at least 2 weeks prior to first administration of study product.
10.If the patient is female, she must be of non-childbearing potential(i.e., either surgically sterilized or 1 year post-menopausal); or, if of childbearing potential, she is using adequate contraception (e.g., intra-uterine contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam). The patient must also have a negative serum pregnancy test at screening and must agree to continue to use adequate contraception during her participation in the study and for 6 months after completion of the vaccination series (i.e., SD71).
11.Can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits),in the opinion of the Investigator.
12.Has provided written informed consent.

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 112
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28

Exclusion criteria:
A patient who meets any of the following criteria will not be enrolled in the study:
1.Has inflammatory rheumatic disease other than RA, including but not limited to, psoriatic arthritis, ankylosingspondyl arthritis, systemic lupus erythematosus, or Lyme disease, that might confound the evaluation of the benefit of study therapy.
2.Has been treated with non-biological DMARDs/systemic immunosuppressives(e.g., D-penicillamine, sulfasalazine, azathioprine, cyclosporine, mycophenolatemofetil) other than MTX or hydroxychloroquine within 4 weeks prior to the first administration of study product.
3.Has been treated with leflunomide within 12 weeks prior to first administration of study product.
4.Has received intra-articular, IM, or intravenous (IV) corticosteroids, including adrenocorticotropic hormone, within 4 weeks prior to first administration of study product.
5.Has received infliximab, etanercept, adalimumab, certolizumab, golimumab; another TNFa antagonist; or rituximab prior to the study.
7.Has been treated with any other biological DMARDs (e.g., tocilizumab, abatacept, anakinra) or with a Janus-activated kinase (JAK) inhibitor within 6 months prior to first study product administration.
8.Has had a non-tuberculous mycobacterial infection or opportunistic infection (e.g., Pneumocystis carinii, aspergillosis) within 6 months prior to first administration of study product.
9.Has received any live virus or bacterial vaccination within 3 months prior to the first administration of study product.
10.Has a serious infection (e.g., hepatitis, pneumonia, pyelonephritis, or sepsis), has been hospitalized for an infection, or has been treated with IV antibiotics for an infection within 2 months prior to the first administration of study product. Less serious infections (e.g., acute upper respiratory tract infection, simple urinary tract infection) may not be considered exclusionary at the discretion of the Investigator.
11.Has ongoing, chronic, or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection (e.g., bronchiectasis); recurrent urinary tract infection (e.g., recurrent pyelonephritis, chronic non remitting cystitis); or an open, draining, or infected skin wound or ulcer.
12.Has a history of or current congestive heart failure, even if well controlled.
13.Has known history of TB.
14.Has positive IFN? TB diagnostic test (Quantiferon Gold) at screening.
15.The Investigator suspects TB based on a chest X-ray conducted at screening or within 3 months prior to first administration of study product.
16.Is human immunodeficiency virus (HIV) antibody-positive, hepatitis C (HCV) antibody-positive, or hepatitis B surface antigen(HBsAg)-positive at screening.
17.Has used any investigational or non-registered drug within 30 days or five half-lives, whichever is longer; or any investigational or non-registered vaccine within 30 days preceding the first dose of study product.
18.Is pregnant or breastfeeding.
19.Has a history of malignant cancer, with the exception of the following cancers, if they have been adequately treated: cervical carcinoma in situ, basal cell carcinoma, localized bladder cancer, or dermatological squamous cell carcinoma.
20.Has a history of allergic disease or reactions likely to be exacerbated by any component of the study product.
21.Has a history of or active lymphoproliferative disease, including lymphoma, or signs suggestive of possible lymphoprol

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

Health Condition(s) or Problem(s) studied

Active Rheumatoid Arthritis
MedDRA version: 16.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

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

Intervention(s)

Product Name: TNF-Kinoid
Product Code: TNF-K
Pharmaceutical Form: Emulsion for injection
INN or Proposed INN: not assigned yet
Current Sponsor code: TNF-K
Other descriptive name: TNF-Kinoid
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Emulsion for injection
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Main Objective: The primary objective of this study is to demonstrate superior clinical efficacy of TNF-K compared to placebo.

Primary end point(s): Change in DAS28-CRP between SD169 and baseline.

Secondary Objective: The secondary objectives of this study are:
•To evaluate the clinical response by assessing disease activity scores and inflammatory markers
•To evaluate immune response parameters (anti-TNFa and anti-KLH antibody titers and anti-TNFa neutralizing capacities)
•To identify correlates between clinical efficacy and immune response parameters
•To assess the safety and reactogenicity of TNF-K

Timepoint(s) of evaluation of this end point: at study day (SD) 169

Secondary Outcome(s)

Secondary end point(s): •ACR20, ACR50, ACR70 response at SD85, SD113 and SD169 versus baseline.
•Clinical response as defined by a = 1.2 decrease in DAS28-CRP score at SD71, SD85, SD113 and SD169 versus baseline.
•Geometric mean titers (GMTs) of anti-TNFa antibodies at SD1, SD29, SD50, SD71, SD85, SD113, and SD169.
•Positive anti-TNFa neutralizing activity at SD85, SD113 and SD169.

Timepoint(s) of evaluation of this end point: at study days (SD): 1, 29, 50, 71, 85, 113, 169

Secondary ID(s)

TNF-K-006

2013-001999-38-BE

Source(s) of Monetary Support

Neovacs SA