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-EE
• Date of registration: 27/11/2014
• 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: 16/12/2014
• Target sample size: 9
• 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, Russian Federation, Spain, United Kingdom

Contacts

• Name: Clinical Study Manager
• Affiliation: Takeda Development Centre Europe Ltd.

• Name: Clinical Study Manager
• Affiliation: Takeda Development Centre Europe Ltd.

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 (<65 years of
age in Czech Republic).
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 more than
12 months prior to Screening will not 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 (20 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 (20 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 mg/week but = 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 6
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

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 jiroveci pneumonia (PJP), formerly known as
pneumocystis carinii pneumonia (PCP) 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.
Evidence of clinically significant respiratory disease on the basis of
review the data from subjects' respiratory assessments including chest
x-ray, lung function test (forced expiratory volume in 1 second [FEV1]
and forced vital capacity [FVC]) by spirometry performed at Screening).
The subjects must have SpO2 =94%, FEV1 and FVC =60 % of predicted
values and an MRC Breathlessness Scale score of less than 4 at
Screening and 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

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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis (RA)
MedDRA version: 18.1 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)

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.

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.

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.

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

Secondary Outcome(s)

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.
• The change in DAS28-CRP from Baseline at all applicable postbaseline
visits.

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

Secondary ID(s)

MT203-2004

2014-002945-23-GB

Source(s) of Monetary Support

Takeda Development Center Americas, Inc

Takeda Development Centre Europe Ltd.