A Study of Mavrilimumab Versus Anti Tumor Necrosis Factor in Subjects With Rheumatoid Arthritis

NCT01715896 | Completed Phase 2 Results DMC

• 1 other identifier: CD-IA-CAM-3001-1107
• Study Type: interventional
• Target: 215
• Locations: 14 countries
• Sites: 39

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Golimumab; Mavrilimumab

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Responses at Day 169

  The ACR20 was defined as greater than or equal to (\>=) 20 percent (%) improvement, in: swollen joint count (SJC) and tender joint count (TJC) and \>=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity (PGA); physician global assessment of disease activity (MDGA); self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (CRP). If CRP was missing and Erythrocyte sedimentation rate (ESR) was present then ESR was to be used.

  Day 169

• Percentage of Participants Who Achieved American College of Rheumatology 50 (ACR50) Responses at Day 169

  The ACR50 was defined as \>=50% improvement, in: SJC and TJC and \>=50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. If CRP was missing and ESR was present then ESR was to be used. The percentage of participants were calculated by logistic regression model method.

  Day 169

• Percentage of Participants Who Achieved American College of Rheumatology 70 (ACR70) Responses at Day 169

  The ACR70 was defined as \>=70% improvement, in: SJC and TJC and \>=70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. If CRP was missing and ESR was present then ESR was to be used. The percentage of participants were calculated by logistic regression model method.

  Day 169

• Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 169

  The DAS28 (CRP) was calculated from the number of SJC and TJC using the 28 joints count, The DAS28(CRP) considers 28 of the 68 TJC and 28 of the 66 SJC and participant's global health (GH) using PGA of disease activity using the visual analogue scale (VAS) of 0 (= best), 100 (= worst) plus levels of CRP (milligram/Liter \[mg/L\]). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) less than (\<) 3.2 = low disease activity, \>=3.2 to 5.1 = moderate to high disease activity and \<2.6= remission. Participants with score less than 2.6 were analysed. The percentage of participants were calculated by logistic regression model method.

  Day 169

• Percentage of Participants Who Achieved Health Assessment Questionnaire Disability Index (HAQ-DI) Score Improvement From Baseline and >= 0.25 at Day 169

  The HAQ-DI: 20-item scale assessing participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arising, eating, hygiene, walking, reaching, grip, and errands/chores over past week. Each item was scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range from 0 to 3; where 0 = least difficulty and 3 = extreme difficulty. Participants with change from baseline more than or equal to (\>=) 0.25 were reported. The percentage of participants were calculated by logistic regression model method.

  Day 169

Secondary Outcomes (25)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

  Baseline up to Day 169

• Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)

  Baseline up to Day 169

• Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)

  Baseline up to Day 169

• Number of Participants With Pulmonary Function Test Values Below Threshold Values Based on Percent Change From Baseline at Day 85 and 169

  Day 85 and 169

• Dyspnea Score at Day 169

  Day 169

Study Arms (2)

Golimumab 50 mg alternating with Placebo

EXPERIMENTAL

Participants received alternating doses of golimumab 50 milligram (mg) (Weeks 0, 4, 8, 12, 16, 20, and 24) and placebo matched to mavrilimumab (Weeks 2, 6, 10, 14, 18, and 22) injections subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Biological: Golimumab 50 mg

Mavrilimumab 100 mg

EXPERIMENTAL

Participants received Mavrilimumab 100 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Biological: Mavrilimumab 100 mg

Interventions

Golimumab 50 mg BIOLOGICAL

Participants received alternating doses of golimumab 50 mg (Weeks 0, 4, 8, 12, 16, 20, and 24) and placebo matched to mavrilimumab (Weeks 2, 6, 10, 14, 18, and 22) injections subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Golimumab 50 mg alternating with Placebo

Mavrilimumab 100 mg BIOLOGICAL

Participants received Mavrilimumab 100 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Also known as: CAM-3001

Mavrilimumab 100 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (39)

Research Site

Ciudad Autonoma Buenos Aires, Argentina

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Córdoba, Argentina

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San Miguel de Tucumán, Argentina

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Barranquilla, Colombia

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Prague, Czechia

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Uherské Hradiště, Czechia

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Zlín, Czechia

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Montpellier, France

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Athens, Greece

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Heraklion, Greece

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Larissa, Greece

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Baja, Hungary

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Balatonfüred, Hungary

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Budapest, Hungary

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Ashkelon, Israel

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Haifa, Israel

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Kfar Saba, Israel

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Petah Tikva, Israel

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Rehovot, Israel

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Mérida, Mexico

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Coimbra, Portugal

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Lisbon, Portugal

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Viseu, Portugal

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Kazan', Russia

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Moscow, Russia

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Saint Petersburg, Russia

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Belgrade, Serbia

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Niška Banja, Serbia

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Bardejov, Slovakia

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Bratislava, Slovakia

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Kosice - Saca, Slovakia

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Barcelona, Spain

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Bilbao, Spain

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Málaga, Spain

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Birkenhead, United Kingdom

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Cambridge, United Kingdom

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Edinburgh, United Kingdom

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London, United Kingdom

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Plymouth, United Kingdom

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MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

golimumab; mavrilimumab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Non-compartmental analyses was not performed for pharmacokinetics parameters due to limited sampling schedule.

Results Point of Contact

• Title: Marius Albulescu, Associate Medical Director
• Organization: MedImmune, LLC

albulescum@medimmune.com

301-398-0000

Study Officials

• Marius Albulescu

  MedImmune Ltd

  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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2012
• First Posted: October 29, 2012
• Study Start: March 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: February 1, 2015
• Last Updated: October 31, 2016
• Results First Posted: October 31, 2016

Record last verified: 2016-09

Locations

AR (3); SL (3); PT (3); GB (5); HU (3); CO (1); ES (3); CZ (3); ME (1); SE (2); IL (5); FR (1); GR (3); RU (3)