Namilumab vs Adalimumab in Participants With Moderate to Severe Early Rheumatoid Arthritis Inadequately Responding to Methotrexate

NCT02393378 | Terminated Phase 2 Results

• 5 other identifiers: MT203-2004U1111-1160-179115/SC/00202014-002945-23REec-2015-1508
• Study Type: interventional
• Target: 7
• Locations: 4 countries
• Sites: 11

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of namilumab in combination with existing methotrexate (MTX) therapy over 24 weeks in participants with moderate to severe early rheumatoid arthritis (RA), diagnosed within 6 months and inadequately controlled by MTX alone.

Conditions

Rheumatoid Arthritis

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Synovitis, Erosion and Bone Marrow Edema (Osteitis) Score at Week 24

  A Magnetic Resonance Imaging (MRI) of Metacarpophalangeal (MCP) and Wrist of the dominant hand was performed at the baseline and at week 24. Change from the Baseline was assessed according to the Outcome Measures in Rheumatoid Arthritis (RA) Clinical Trials RA-MRI scoring (OMERACT RAMRIS) Standard. RAMRIS score is the sum of its core components: Synovitis Score, Edema Score, and Erosion Score. Synovitis is scored from 0 (normal) to 9 (maximum distension of synovial cavity). Edema is scored 0 (normal) to 69 (maximum articular bone involvement). Erosion is scored from 0 (normal) to 230 (maximum erosion of articular bone). Total RAMRIS score=0 (normal), maximum RAMRIS score=308 (severe structural damage). For Synovial Score, Edema Score, Erosion Score, and RAMRIS score, increasing number = increasing severity.

  Baseline and Week 24

Secondary Outcomes (5)

• Change From Baseline in Dynamic Contrast-enhanced - Magnetic Resonance Imaging (DCE-MRI) Parameters at Week 24

  Baseline and Week 24

• Number of Participants Who Achieved Remission at Week 24

  Week 24

• Number of Participants Who Achieved Low Disease Activity at Week 24

  Week 24

• Number of Participants Who Achieved ACR 20, 50, and 70 at Week 24

  Week 24

• Change From Baseline in DAS28-CRP Score

  Baseline Up to Week 42

Study Arms (2)

Adalimumab 40 mg

EXPERIMENTAL

Adalimumab 40 mg, subcutaneous (SC) injection at Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22 as an add-on to weekly existing stable MTX and folic acid as per prescribed medication.

Drug: Adalimumab; Drug: Methotrexate; Drug: Folic Acid

Namilumab 150 mg

ACTIVE COMPARATOR

Namilumab 150\*2 mg, SC injection at Week 0 followed by 150 mg, SC injections at Weeks 2, 6, 10, 14, 18, and 22 as an add-on to weekly existing stable MTX and folic acid as per prescribed medication.

Drug: Namilumab; Drug: Methotrexate; Drug: Folic Acid

Interventions

Namilumab DRUG

Namilumab injection

Namilumab 150 mg

Adalimumab DRUG

Adalimumab SC injection

Adalimumab 40 mg

Methotrexate DRUG

Methotrexate tablet

Adalimumab 40 mg; Namilumab 150 mg

Folic Acid DRUG

Folic Acid Tablet

Adalimumab 40 mg; Namilumab 150 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is diagnosed with adult onset rheumatoid arthritis (RA) as defined by the 2010 The American College of Rheumatology (ACR)/The European League Against Rheumatism criteria for the classification of RA within 6 months prior to Screening Visit.
• Has active disease defined as:
• swollen joint count ≥4 and tender joint count ≥4 (referred to the 28 joint-count system) at Screening and Baseline Visits, and
• C-reactive protein ≥4.3 mg/L and erythrocyte sedimentation rate ≥28 mm/hr at Baseline Visits, and
• imaging (ultrasound power doppler) evidence of moderate to severe inflammation of at least 1 joint of the dominant hand metacarpophalangeal (MCP) and/or wrist) at Screening and Baseline Visits.
• Is receiving current treatment with Methotrexate (MTX) for RA.
• Received MTX for at least 3 months prior to the Screening Visit.
• 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 the Baseline Visit, OR
• Participants on a stable dose for at least 8 weeks of MTX of ≥7.5 mg/week, if the MTX dose has been reduced for reasons of documented intolerance to MTX.
• 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 co-medication for MTX treatment).
• Has a posterior, anterior, and lateral chest x-ray obtained within the last 3 months before Screening or at the Screening visit without any signs of clinically significant pulmonary disease.

You may not qualify if:

• Has received biologic disease-modifying antirheumatic drugs for the treatment of RA.
• Have a history of or currently inflammatory joint disease other than RA (e.g., 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).
• Has any major systemic features of RA, for example, Felty's syndrome, vasculitis, or interstitial fibrosis of the lungs.
• Diagnosed with primary fibromyalgia that would make it difficult to appropriately assess RA activity for the purposes of this study or a diagnosis of any systemic inflammatory condition other than RA.
• Has a history of juvenile idiopathic arthritis or RA onset prior to age 16 years.
• Required to take excluded medications
• Not willing to take folic/folinic acid (as part of MTX regimen, according to country-specific practices) in order to minimize toxicity.
• Has an underlying condition that predisposes to infections (e.g., immunodeficiency, poorly controlled diabetes history, splenectomy).
• 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.
• Presence or history of active tuberculosis (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.
• 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.
• 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.
• 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.
• 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.
• Has an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2.History of MTX-associated lung toxicity.

Sponsors & Collaborators

• Takeda: lead

Study Sites (13)

Unknown Facility

Pardubice, Czechia

Location

Unknown Facility

Prague, Czechia

Location

Unknown Facility

Tallinn, Estonia

Location

Unknown Facility

Tartu, Estonia

Location

Unknown Facility

Moscow, Russia

Location

Unknown Facility

Yaroslavl, Russia

Location

Unknown Facility

Santiago de Compostela, La Coruna, Spain

Location

Unknown Facility

Fuenlabrada, Madrid, Spain

Location

Unknown Facility

A Coruña, Spain

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

London, Greater London, United Kingdom

Location

Unknown Facility

Salford, Greater Manchester, United Kingdom

Location

Unknown Facility

Oxford, Oxfordshire, United Kingdom

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

namilumab; Adalimumab; Methotrexate; Folic Acid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2015
• First Posted: March 19, 2015
• Study Start: April 8, 2015
• Primary Completion: June 27, 2016
• Study Completion: November 16, 2016
• Last Updated: February 5, 2019
• Results First Posted: February 5, 2019

Record last verified: 2018-08

Locations

CZ (2); RU (2); GB (3); ES (4)