A 24-week placebo-controlled clinical study to evaluate the adequate dose, efficacy and safety of 3 doses of namilumab combined with methotrexate in subjects with moderate to severe rheumatoid arthritis followed by a 48-week active extension study.

Phase 1

Conditions: Rheumatoid Arthritis (RA)
MedDRA version: 18.0Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2013-002805-76-DE

Lead Sponsor: Takeda Development Centre Europe Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 324

Inclusion Criteria

1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
2. The subject or, when applicable, the subject’s legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. The subject is male or female and aged 18 years (20 years in Japan) or older (65 years maximum in Czech Republic) at time of signing the informed consent form.*
4. The subject must have adult onset RA as defined by the 2010 ACR/EULAR criteria for the classification of RA for at least 6 months prior to Screening Visit.
5. The subject must have active disease defined as:
a) At least moderately active disease defined by DAS28(CRP)=3.2 at screening and
DAS28(ESR) =3.2 at baseline visit [Day 1] and Swollen joint count (SJC) =4 (within the 28 joints from DAS 28) at both
the Screening and baseline [Day 1] Visits.
6. VAS pain >40 mm as measured using the 100 mm study site electronic VAS scale at the Screening Visit and baseline [Day 1] visit.
7. Currently receiving treatment for RA with MTX, and
• Has received weekly MTX for at least 3 months prior to the Screening Visit AND
• Has received treatment with 15mg/week = MTX = 25 mg/week (6mg/week = MTX = 16mg/week in Japan) at a stable dose via the same route of administration and formulation for at least 8 weeks prior to baseline [Day 1]
Visit OR
For patients outside Japan a stable dose for at least 8 weeks of MTX of =7,5 mg/week is acceptable, if the MTX dose has been reduced for reasons of documented intolerance to MTX, eg hepatic or hematological toxicity documented in eCRF, or per local requirement.
8. Willing to continue or initiate treatment with oral folic acid (at least 5 mg/week) or equivalent and be treated during the entire study (mandatory co-medication for MTX treatment).
9. Must have a posterior, anterior (PA) and lateral chest x-ray either obtained within 3 months prior to screening, or recorded during screening.
10. A female subject of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of the informed consent throughout the duration of the study until the end of the safety follow up (18 weeks after last dose), see Section 9.1.15.
11. A male subject who is non-sterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of the informed consent throughout the duration of the study until the end of the safety follow up (18 weeks after last dose), see Section 9.1.15.
12. The subject is able and willing to complete questionnaires at home using an electronic device in an approved language.
13. Either MTX-IR subject per definition on section 6.0 of the protocol or TNF-IR subject per definition on section 6.0 of the protocol.
*Due to local requirements in Czech Republic, only patients under 65 years of age can be enrolled into the study.
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 260
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 64

Exclusion Criteria

1. Subjects <18 years of age (< 20 Years in Japan) or less than legal adult age in the country of the study site, whichever is higher. Subjects > 65 years of age in Czech Republic.
2. S. has received any investigational compound within 30 days, or within 5 half lives (whichever is longer) prior to Screening Visit, or is participating or plans to participate in any other clinical study during this study.
3. S. has a history of or currently has any inflammatory joint disease other than RA (eg gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy or Lyme disease) or other systemic autoimmune disorder (eg systemic lupus erythematosus (SLE), inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease or other overlap syndrome).
4. S. has any major systemic features of RA, eg Felty’s syndrome, vasculitis or interstitial fibrosis of the lungs.
5. S. has diagnosis of primary fibromyalgia that would make it difficult to appropriately assess RA activity for the purposes of this study.
6. History of juvenile idiopathic arthritis or arthritis onset prior to age 16.
7. S. is required to take excluded medications (Section 7.3)
8. S. with any of the following laboratory abnormalities at screening visit (identified by central laboratory):
a) Hemoglobin <8.5 g/dL
b) Neutrophils <1500/mm3.
c) Platelet count <75 000 cells/mm3.
d) AST or ALT >1.5 x ULN.
e) Bilirubin (total) >ULN, unless Gilbert’s disease has been determined by genetic testing and has been documented.
9. S has history of hypersensitivity or allergies to any of the contents of the formulation (see IB [13].
10. S. has any clinically significant illness, including infection requiring antibiotics, within 4 weeks prior to first dose of study medication, which may influence outcome of the study.
11. S. has underlying condition that predisposes to infections (eg immunodeficiency, poorly controlled diabetes history, splenectomy).
12. Evidence of clinically significant respiratory disease, on the basis of review the data from subjects’ respiratory assessments, including chest x-ray, lung function test, PFT (forced expiratory volume in one second [FEV1] and forced vital capacity [FVC]) by spirometry performed at screening). Subjects must have SpO2 =94%, FEV1 and FVC =60 % of predicted values at Screening and at baseline and no uncontrolled lung disease. Subject’s treatment which has been modified to control lung disease within 24 weeks prior screening is exclusionary.
13. History of clinically significant interstitial lung disease (ILD) eg history of chronic or recurrent pulmonary infection where macrophages are important for clearance of the infection eg pneumocystis jiroveci pnuemonia (PJP) formerly known as pneumocystis carinii pneumonia (PCP) Japanese + Korean patients will be tested using Beta glucans test and subjects will be excluded unless Beta Glucans test is negativ (54), allergic bronchopulmonary aspergillosis (ABPA), nocardia infections, Actinomyces infection.
14. Presence or history of active TB or latent TB infection, where no anti-TB treatment has been given or where successful completion of an appropriate course of anti- TB therapy cannot be documented.
15. Positive QuantiFERON-TB Gold test and / or evidence of active or latent TB by chest X-ray, not accompanied by initiation of an approved regimen of anti-TB therapy at least 12 months prior to baseline visit.
16. S. has a known history of infection wi