A 24 week Phase 2 study in subjects with moderate to severe early Rheumatoid Arthritis who?s symptoms are not fully controlled by treatment with methotrexate alone. Subjects will be told if they are in the group receiving either 150 mg namilumab injected under the skin or adalimumab. Responses to the medicine will be measured using MRI.

• Register: EUCTR
• Last refreshed on: 9 January 2017
• Main ID: EUCTR2014-002945-23-ES
• Date of registration: 09/02/2015
• Prospective Registration: Yes
• Primary sponsor: Takeda Development Centre Europe Ltd.
• Public title: A 24 week Phase 2 study in subjects with moderate to severe early Rheumatoid Arthritis who?s symptoms are not fully controlled by treatment with methotrexate alone. Subjects will be told if they are in the group receiving either 150 mg namilumab injected under the skin or adalimumab. Responses to the medicine will be measured using MRI.
• Scientific title: A 24-week Randomized, Open-Label, Parallel-Group, Active-Controlled, Exploratory, Proof-of-Mechanism Imaging Study Investigating the Efficacy of 150 mg of Namilumab Administered Subcutaneously vs Adalimumab in Patients With Moderate to Severe Early Rheumatoid Arthritis Inadequately Responding to Methotrexate - A Phase 2 Study of Namilumab vs Anti-Tumor Necrosis Factor in Patients With Rhematoid Arthritis.
• Date of first enrolment: 30/04/2015
• Target sample size: 36
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002945-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, Estonia, Latvia, Russian Federation, Spain, United Kingdom

Contacts

• Name: Departamento Regulatory-Start Up
• Affiliation: QUINTILES SL

• Name: Departamento Regulatory-Start Up
• Affiliation: QUINTILES SL

Key inclusion & exclusion criteria

Inclusion criteria:
Subject eligibility is determined according to the following criteria prior to entry into the study:
The subject is male or female and aged 18 years, or above.
The subject is diagnosed with adult onset RA as defined by the 2010 ACR/EULAR criteria for the classification of RA within 6 months prior to Screening Visit. Subjects with onset of signs and symptoms within 12 months prior to Screening will be allowed into the study.
The subject has active disease defined as:
a) Swollen joint count (SJC) ? 4 and tender joint count (TJC) ? 4 (referred to the 28 joint-count system) at Screening and Baseline Visit
and
b) C-reactive protein (CRP) ?4.3 mg/L at Screening Visit and erythrocyte sedimentation rate (ESR) ?28 mm/hr at Baseline Visit.
and
c) Imaging (US power doppler) evidence of moderate to severe inflammation of at least 1 MCP joint of the dominant hand and/or 1 joint of the dominant wrist at Screening and Baseline Visit.
A male subject who is nonsterilized* and sexually active with a female partner of childbearing potential* agrees to use adequate contraception* from signing of informed consent throughout the duration of the study until the end of the safety follow up (18 weeks after last dose).
A female subject of childbearing potential* who is sexually active with a nonsterilized* male partner agrees to use routinely adequate contraception* from signing of informed consent throughout the duration of the study until the end of the safety follow up (18 weeks after last dose).
The subject is receiving current treatment with MTX for RA:
? Received weekly MTX for at least 3 months prior to the Screening Visit, AND
? Received treatment with MTX ?15 to 25 mg/week at a stable dose via the same route of administration and formulation for at least 8 weeks prior to Baseline Visit, OR
? 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.
The subject is willing to continue or initiate treatment with oral folic acid (at least 5 mg/week) or equivalent and be treated during the entire trial (mandatory comedication for MTX treatment).
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 26
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
Subjects <18 years of age or less than the legal adult age in the country of the study site, whichever is higher.
The subject has received biologic DMARDs for the treatment of RA.
The subject has a history of or currently 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, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease, or other overlap syndrome).
The subject has any major systemic features of RA, for example, Felty?s syndrome, vasculitis, or interstitial fibrosis of the lungs.
The subject has a history of juvenile idiopathic arthritis or RA onset prior to age 16 years.
The subject has an underlying condition that predisposes to infections (eg, immunodeficiency, poorly controlled diabetes history, splenectomy).
The subject has a history of clinically significant interstitial lung disease, for example, history of chronic or recurrent pulmonary infection where macrophages are important for the clearance of the infection, for example, pneumocystis carinii pneumonia, allergic bronchopulmonary aspergillosis, nocardia infections, Actinomyces infection.
The subject has a positive QuantiFERON-TB Gold test and/or evidence of active or latent TB by chest x-ray at Screening Visit, not accompanied by initiation of an approved regimen of anti-TB therapy at least 12 months prior to the Baseline Visit.
The subject has a known history of infection with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV), or has serological findings at the Screening Visit which indicate active or latent hepatitis B, hepatitis C or HIV infection.
The subject has a clinically relevant decrease in lung function at Screening, as defined by an oxygen saturation as measured by pulse oximetry (SpO2) <94% at rest.
The subject has evidence of clinically significant respiratory disease on the basis of review the data from subjects? respiratory assessments including chest x-ray, pulmonary function test (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]) by spirometry performed at Screening). To be eligible for the study, subjects must have SpO2 ?94%, FEV1 and/or FVC ?60 % of predicted values at Screening or at Baseline and no uncontrolled lung disease. A subject?s treatment that has been modified to control lung disease within 24 weeks prior to Screening is exclusionary.
The subject has a history of severe chronic obstructive pulmonary disease (COPD) and/or history of severe COPD exacerbation(s), or a history of asthma with exacerbations requiring hospitalization, within the last 12 months prior to the Screening Visit.
The subject has an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2.
The subjects has a history or evidence of a clinically significant disorder (including but not limited to cardiopulmonary, oncologic, renal, metabolic, hematologic or psychiatric), condition or disease that, in the opinion of the investigator and Takeda physician, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
The subject has any significant cardiac disease (eg, coronary artery disease with 7. unstable angina, coronary heart failure New York Heart Association Class III and IV, familial long QT syndrome).
The subject has a history of cancer within the last 10

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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis (RA)
MedDRA version: 18.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: Namilumab
Product Code: MT203
Pharmaceutical Form: Solution for injection
INN or Proposed INN: namilumab
CAS Number: 1206681-39-1
Current Sponsor code: MT203
Other descriptive name: NAMILUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-

Trade Name: Humira 40 mg solution for injection in pre-filled syringe
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 24

Main Objective: To explore the effect on structural damage image markers measured as change from Baseline in synovitis, erosion, and bone marrow edema (osteitis), in metacarpophalangeal (MCP) joints and wrist at Week 24 on magnetic resonance imaging (MRI) using the RA-MRI scoring (RAMRIS) Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) score.

Primary end point(s): ? Change from Baseline in synovitis, erosion and bone marrow edema (osteitis), on MRI of the MCP and wrist using the RAMRIS OMERACT at Week 24.

Secondary Objective: ? To explore the effect on structural damage imaging markers measured as change from Baseline in DCE-MRI parameters at Week 24 on MCP joints and wrist using the DCE-MRI.
? To explore other clinical efficacy outcomes of namilumab in RA such as Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) and American College of Rheumatology (ACR) 20, 50, and 70 criteria.
? To explore the speed of onset of efficacy measured as effect on synovitis, bone marrow edema, erosion (RAMRIS), and synovial perfusion using static and DCE-MRI at Weeks 6 and 12.
? To evaluate the safety and tolerability of namilumab/MTX coadministration.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Please see E.5.2 for timepoints corresponding to each secondary
endpoint.

Secondary end point(s): ? Vascular perfusion of the synovium measured as a change from Baseline in DCE-MRI parameters at Week 24. The ability to induce synovial remission (absence of synovial inflammation) will be assessed at Weeks 6 and 12 using static (RAMRIS OMERACT synovitis score) and DCE-MRI parameters.
? Proportion of subjects who achieved DAS28-CRP (<2.6) remission at Week 24.
? Proportion of subjects who achieved DAS28-CRP (<3.2) low disease activity by at Week 24.
? Proportion of subjects who achieved ACR 20, 50, and 70 at Week 24.
? Clinical disease activity improvement measured as decrease in DAS28-CRP from Baseline at all applicable postbaseline visits.

Secondary ID(s)

MT203-2004

2014-002945-23-GB

Source(s) of Monetary Support

Takeda Development Centre Europe Ltd.

Takeda Development Center Americas, Inc