Clinical trial NCT01715896: A Study of Mavrilimumab Versus Anti Tumor Necrosis Factor in Subjects With Rheumatoid Arthritis
Official title: A Phase 2 Exploratory Study of Mavrilimumab Versus Anti-tumor Necrosis Factor in Subjects With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Golimumab
Mavrilimumab
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2012-10-29
Enrollment: 215
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives of this study is to explore the efficacy of mavrilimumab compared with golimumab in the treatment of adult subjects 18-80 years of age with moderate-to-severe active rheumatoid arthritis (RA) who have an inadequate response to one or more conventional disease-modifying anti-rheumatic drugs (DMARDs) and/or one or two anti-tumor necrosis factor (TNF) agents (excluding golimumab) for efficacy or safety reasons.

Detailed description: Despite the therapeutic improvements with recent biologic agents approved for rheumatoid arthritis (RA), there is still a significant unmet medical need for the treatment of subjects with this chronic disease to achieve a faster, more complete response, and higher rates of remission. The aim of the current study is to compare the efficacy and safety of a subcutaneous dose of mavrilimumab with a marketed treatment for RA (golimumab) in 120 adult subjects with moderate-to-severe active RA who have had an inadequate response to one or two anti-TNF agents with mavrilimumab. The design of the study was exploratory and not formerly statistically powered.

Eligibility criteria: Inclusion Criteria:

* Age 18 through 80 years
* Written consent
* Diagnosis of adult onset Rheumatoid Arthritis (RA) as defined by the 2010 American College of Rheumatology European League Against Rheumatism (ACR/EULAR) classification criteria
* Moderately active disease as defined by disease activity score in 28 joints C-reactive protein (DAS28\[CRP\]) greater than or equal to (\>=) 3.2 at screening and DAS28 erythrocyte sedimentation rate(ESR) ≥ 3.2 at Day 1
* Inadequate response to one or more conventional disease-modifying anti-rheumatic drugs (DMARDs)
* At least 4 swollen joints
* Inadequate response to one or two anti-TNF agents other than the study comparator, as defined by the protocol
* Receiving oral or injectable methotrexate, as defined by the protocol.

Exclusion Criteria:

* A rheumatic autoimmune disease or other inflammatory joint disease other than RA
* Previous treatment with biologic therapies other than anti-TNF for RA
* Treatment with other DMARDs or non-steroidal anti-inflammatory drugs (NSAIDs), as defined by the protocol.
* Medical history as defined by the protocol.

Primary outcomes:
measure: Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Responses at Day 169
timeFrame: Day 169
measure: Percentage of Participants Who Achieved American College of Rheumatology 50 (ACR50) Responses at Day 169
timeFrame: Day 169
measure: Percentage of Participants Who Achieved American College of Rheumatology 70 (ACR70) Responses at Day 169
timeFrame: Day 169
measure: Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 169
timeFrame: Day 169
measure: Percentage of Participants Who Achieved Health Assessment Questionnaire Disability Index (HAQ-DI) Score Improvement From Baseline and >= 0.25 at Day 169
timeFrame: Day 169
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: Baseline up to Day 169
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Day 169
measure: Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Day 169
measure: Number of Participants With Pulmonary Function Test Values Below Threshold Values Based on Percent Change From Baseline at Day 85 and 169
timeFrame: Day 85 and 169
measure: Dyspnea Score at Day 169
timeFrame: Day 169
measure: Change From Baseline in Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Score at Day 169
timeFrame: Baseline and Day 169
measure: Change From Baseline in Continuous American College of Rheumatology (ACRn) Score at Day 169
timeFrame: Baseline up to Day 169
measure: American College of Rheumatology (ACR) Hybrid Score at Day 169
timeFrame: Day 169
measure: Number of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 169
timeFrame: Day 169
measure: Number of Participants With DAS28 (CRP) Remission and Low Disease Activity at Day 169
timeFrame: Day 169
measure: Time to Onset DAS28 (CRP) Remission at Day 169
timeFrame: Day 169
measure: Duration of DAS28 (CRP) Remission at Day 169
timeFrame: Day 169
measure: Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) < 2.6 at Day 169
timeFrame: Day 169
measure: Percentage of Participants Who Achieved Simplified Disease Activity Index (SDAI) Remission at Day 169
timeFrame: Day 169
measure: Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Day 169
timeFrame: Day 169
measure: Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission at Day 169
timeFrame: Day 169
measure: Mean Change From Baseline in Swollen and Tender Joint Count at Day 169
timeFrame: Baseline and Day 169
measure: Mean Change From Baseline in Patient Assessment of Pain at Day 169
timeFrame: Baseline and Day 169
measure: Mean Change From Baseline in Patient Global Assessment (PGA) of Disease Activity at Day 169
timeFrame: Baseline and Day 169
measure: Mean Change From Baseline in Physician Global Assessment of Disease Activity (MDGA) at Day 169
timeFrame: Baseline and Day 169
measure: Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Day 169
timeFrame: Baseline and Day 169
measure: Ratio of Change C-Reactive Protein (CRP) at Day 169 to Baseline
timeFrame: Baseline and Day 169
measure: Erythrocyte Sedimentation Rate (ESR) at Day 169
timeFrame: Day 169
measure: Serum Concentrations of Mavrilimumab
timeFrame: Baseline, Day 8, 15, 29, 85, 141, and 169
measure: Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab
timeFrame: Day 1 to Day 169
Other outcomes:
Locations:
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Research Site
city: Cordoba
country: Argentina
facility: Research Site
city: San Miguel de Tucuman
country: Argentina
facility: Research Site
city: Barranquilla
country: Colombia
facility: Research Site
city: Praha 2
country: Czech Republic
facility: Research Site
city: Uherske Hradiste
country: Czech Republic
facility: Research Site
city: Zlin
country: Czech Republic
facility: Research Site
city: Montpellier cedex 5
country: France
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Heraklion
country: Greece
facility: Research Site
city: Larissa
country: Greece
facility: Research Site
city: Baja
country: Hungary
facility: Research Site
city: Balatonfured
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Ashkelon
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Kfar-Saba
country: Israel
facility: Research Site
city: Petach-Tikva
country: Israel
facility: Research Site
city: Rehovot
country: Israel
facility: Research Site
city: Merida
country: Mexico
facility: Research Site
city: Coimbra
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Viseu
country: Portugal
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Niska Banja
country: Serbia
facility: Research Site
city: Bardejov
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Kosice - Saca
country: Slovakia
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Bilbao
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Birkenhead
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Plymouth
country: United Kingdom
facility: Research Site
Study officials:
affiliation: MedImmune Ltd
name: Marius Albulescu
role: STUDY_DIRECTOR
References: