A Study to Evaluate the Efficacy and Safety of CAM-3001 (Drug) in Subjects With Rheumatoid Arthritis

NCT01050998 | Completed Phase 2 Results

• 1 other identifier: MI-CP219
• Study Type: interventional
• Target: 516
• Locations: 11 countries
• Sites: 55

Brief Summary

The primary objectives of this study is to assess the safety, tolerability and efficacy of multiple doses of the mavrilimumab (CAM-3001) administered subcutaneously in subjects with moderately active Rheumatoid Arthritis (RA).

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Mavrilimumab; CAM-3001

Outcome Measures

Primary Outcomes (24)

• Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85

  DAS28 (CRP) calculated swollen joint count (SJC) and tender joint count (TJC) using the 28 joints, general health (GH) using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and CRP (milligram per Liter \[mg/L\]). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) less than (\<) 3.2 = low disease activity, greater than or equal to (\>=) 3.2 to 5.1 = moderate to high disease activity and \<2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (CRP) score at Day 85.

  Day 85

• Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85 by Region

  DAS28 (CRP) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and CRP (mg/L). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) \<3.2 = low disease activity, \>=3.2 to 5.1 = moderate to high disease activity and \<2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (CRP) score at Day 85. DAS28 (CRP) response at Day 85 for the European and Japanese regions were reported.

  Day 85

• Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85

  DAS28 (ESR) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]). Total score range: 0-9.4, higher score = more disease activity. DAS28 (ESR) \<3.2 = low disease activity, \>=3.2 to 5.1 = moderate to high disease activity and \<2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (ESR) score at Day 85.

  Day 85

• Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85 by Region

  DAS28 (ESR) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]). Total score range: 0-9.4, higher score = more disease activity. DAS28 (ESR) \<3.2 = low disease activity, \>=3.2 to 5.1 = moderate to high disease activity and \<2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (ESR) score at Day 85. DAS28 (ESR) response at Day 85 for the European and Japanese regions were reported.

  Day 85

• Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85

  DAS28 (CRP) response by EULAR category were used to measure individual response as none, moderate, and good, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline \>1.2 with baseline DAS28 (CRP) \<3.2; moderate response: change from baseline \>1.2 with baseline DAS28 (CRP) \>=3.2 to less than or equal to (=\<) 5.1 or change from baseline \>=0.6 to =\< 1.2 with baseline DAS28 (CRP) \>=3.2 to =\<5.1; no response: change from baseline \<0.6 or change from baseline \>=0.6 and =\<1.2 with baseline DAS28 (CRP) \>5.1.

  Day 85

• Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region

  DAS28 (CRP) response by EULAR category were used to measure individual response as none, moderate, and good, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline \>1.2 with baseline DAS28 (CRP) \<3.2; moderate response: change from baseline \>1.2 with baseline DAS28 (CRP) \>=3.2 to =\< 5.1 or change from baseline \>=0.6 to =\< 1.2 with baseline DAS28 (CRP) \>=3.2 to =\<5.1; no response: change from baseline \<0.6 or change from baseline \>=0.6 and =\<1.2 with baseline DAS28 (CRP) \>5.1. DAS28 (CRP) response by EULAR category at Day 85 for the European and Japanese regions were reported.

  Day 85

• Percentage of Participants Who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85

  DAS28 (ESR) response by EULAR category were used to measure individual response as none, moderate, and good, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline \>1.2 with baseline DAS28 (ESR) \<3.2; moderate response: change from baseline \>1.2 with baseline DAS28 (ESR) \>=3.2 to =\< 5.1 or change from baseline \>=0.6 to =\< 1.2 with baseline DAS28 (ESR) \>=3.2 to =\<5.1; no response: change from baseline \<0.6 or change from baseline \>=0.6 and =\<1.2 with baseline DAS28 (ESR) \>5.1.

  Day 85

• Percentage of Participants Who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region

  DAS28 (ESR) response by EULAR category were used to measure individual response as none, moderate, and good, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline \>1.2 with baseline DAS28 (ESR) \<3.2; moderate response: change from baseline \>1.2 with baseline DAS28 (ESR) \>=3.2 to =\< 5.1 or change from baseline \>=0.6 to =\< 1.2 with baseline DAS28 (ESR) \>=3.2 to =\<5.1; no response: change from baseline \<0.6 or change from baseline \>=0.6 and =\<1.2 with baseline DAS28 (ESR) \>5.1. DAS28 (ESR) response by EULAR category at Day 85 for the European and Japanese regions were reported.

  Day 85

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

  An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up Day 169 that were absent before treatment or that worsened relative to pretreatment state.

  Baseline up to Day 169 (follow-up)

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

  Vital sign assessments included blood pressure, pulse rate, temperature, and respiration rate. Vital signs abnormalities reported as TEAEs were reported.

  Baseline up to Day 169 (follow-up)

• Number of Participants With Abnormal Electrocardiogram (ECG) Results

  12-lead ECG was recorded and corrected QT (QTc) interval was measured with the participant in a rested supine position for at least 10 minutes. Any ECG abnormality deemed clinically significant as per investigator's discretion were reported.

  Baseline up to Day 169 (follow-up)

• Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85

  FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.

  Day 85

• Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 by Region

  FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FEV1 and FVC at Day 85 for the European and Japanese regions were reported.

  Day 85

• Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85

  FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.

  Baseline and Day 85

• Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85

  DLCO is a pulmonary function test that measures the partial pressure difference between inspired and expired carbon monoxide.

  Day 85

• Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 by Region

  DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. DLCO% for the European and Japanese regions were reported.

  Day 85

• Change From Baseline in Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85

  DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide.

  Baseline and Day 85

• Dyspnea Score at Day 85

  Modified Borg dyspnea scale is a validated participant reported outcome assessing participant's perceived difficulty in breathing (dyspnea). The scale ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicate greater difficulty in breathing.

  Day 85

• Change From Baseline in Dyspnea Score at Day 85

  Modified Borg dyspnea scale is a validated participant reported outcome assessing participant's perceived difficulty in breathing (dyspnea). The scale ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicate greater difficulty in breathing.

  Baseline and Day 85

• Categorized Dyspnea Score at Day 85

  Modified Borg dyspnea scale is a validated participant reported outcome assessing participant's perceived difficulty in breathing (dyspnea). The scale ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicate greater difficulty in breathing. The modified BORG dyspnea scale was categorized as - no/slight (0 to 2), moderate (3 and 4), severe (5 and 6) and very severe breathlessness (7 and above).

  Day 85

• Oxygen Saturation Level at Day 85

  Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood.

  Day 85

• Oxygen Saturation Level at Day 85 by Region

  Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood. Oxygen saturation for the European and Japanese regions were reported.

  Day 85

• Change From Baseline in Oxygen Saturation Level at Day 85

  Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood.

  Baseline and Day 85

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

  Any medically significant change in laboratory evaluations were recorded as adverse events. Following parameters were analyzed for laboratory examination: hematology (haemoglobin, reticulocytes, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, mean corpuscular volume, mean corpuscular haemoglobin concentration); serum chemistry (creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, gamma glutamyl transferase, CRP, ESR, albumin, total cholesterol, triglycerides, rheumatoid factor and anti-cyclic citrullinated peptide antibodies); urinalysis (albumin, glucose, protein, blood, nitrite).

  Baseline up to Day 169 (follow-up)

Secondary Outcomes (41)

• Change From Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85

  Baseline and Day 85

• Change From Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85 by Region

  Baseline and Day 85

• Percentage of Participants Who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85

  Day 85

• Percentage of Participants Who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85 by Region

  Day 85

• Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission

  Baseline up to Day 169 (follow-up)

Study Arms (5)

Mavrilimumab 10 mg

EXPERIMENTAL

Mavrilimumab (CAM-3001) 10 milligram (mg) injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Biological: Mavrilimumab 10 mg

Mavrilimumab 30 mg

EXPERIMENTAL

Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Biological: Mavrilimumab 30 mg

Mavrilimumab 50 mg

EXPERIMENTAL

Mavrilimumab (CAM-3001) 50 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Biological: Mavrilimumab 50 mg

Mavrilimumab 100 mg

EXPERIMENTAL

Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Biological: Mavrilimumab 100 mg

Placebo

PLACEBO COMPARATOR

Placebo matched to mavrilimumab injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Other: Placebo

Interventions

Mavrilimumab 10 mg BIOLOGICAL

Mavrilimumab (CAM-3001) 10 mg injection subcutaneously every other week for 12 weeks.

Also known as: CAM-3001

Mavrilimumab 10 mg

Mavrilimumab 30 mg BIOLOGICAL

Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every other week for 12 weeks.

Also known as: CAM-3001

Mavrilimumab 30 mg

Mavrilimumab 50 mg BIOLOGICAL

Mavrilimumab (CAM-3001) 50 mg injection subcutaneously every other week for 12 weeks.

Also known as: CAM-3001

Mavrilimumab 50 mg

Mavrilimumab 100 mg BIOLOGICAL

Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every other week for 12 weeks.

Also known as: CAM-3001

Mavrilimumab 100 mg

Placebo OTHER

Placebo matched to mavrilimumab injection subcutaneously every other week for 12 weeks.

Placebo

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 (20 to 75 years in Japan)
• Written consent
• Diagnosis of adult onset Rheumatoid Arthritis (RA) of at least 3 months duration as defined by the 1987 American College of Rheumatology (ACR) classification criteria (Arnett et al, 1988)
• Treatment with methotrexate at a stable and tolerated doses
• Positive anti-cyclic citrullinated peptide (CCP) immuno-globulin G antibodies (more than \[\>\] 5 international unit per milliliter \[IU/mL\]) and/or rheumatoid factor (RF \>14 IU/mL) at screening
• Received more than or equal to (\>=) 5 milligram (mg) per week folic acid as a single or divided dose during the study.

You may not qualify if:

• A rheumatic autoimmune disease other than RA
• A history of, or current, inflammatory joint disease other than RA or other systemic autoimmune disorder
• Subjects at a high risk of infection
• Subjects (male and female) of reproductive potential who are not willing to use contraception from screening through the end date of the trial
• History of methotrexate or any drug-induced lung fibrosis or pneumonitis.

Sponsors & Collaborators

• MedImmune LLC: lead
• MedImmune Ltd: collaborator

Study Sites (55)

Research Site

Plovdiv, Bulgaria

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Sofia, Bulgaria

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Varna, Bulgaria

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Bruntál, Czechia

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Ostrava - Trebovice, Czechia

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Prague, Czechia

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Praha 4 - Nusle, Czechia

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Uherské Hradiště, Czechia

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Zlín, Czechia

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Tallinn, Estonia

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Budapest, Hungary

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Sopron, Hungary

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Zalaegerszeg, Hungary

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Chiba, Japan

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Chiyoda-ku, Japan

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Fukui-shi, Japan

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Fukuoka, Japan

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Goshogawara-shi, Japan

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Hamamatsu, Japan

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Iizuka-shi, Japan

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Kagoshima, Japan

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Kasama-shi, Japan

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Kitakyushu-shi, Japan

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Nagano, Japan

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Nagoya, Japan

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Okayama, Japan

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Omura-shi, Japan

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Sagamihara-shi, Japan

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Sasebo-shi, Japan

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Shinjuku-ku, Japan

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Liepāja, Latvia

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Riga, Latvia

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Valmiera, Latvia

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Klaipėda, Lithuania

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Vilnius, Lithuania

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Bialystok, Poland

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Bydgoszcz, Poland

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Katowice, Poland

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Legnica, Poland

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Lublin, Poland

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Poznan, Poland

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Torun, Poland

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Warsaw, Poland

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Bucharest, Romania

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Ploieşti, Romania

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Târgu Mureş, Romania

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Barnaul, Russia

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Kazan', Russia

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Kemerovo, Russia

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Novosibirsk, Russia

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Saint Petersburg, Russia

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Yaroslavl, Russia

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Donetsk, Ukraine

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Kiev, Ukraine

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Kyiv, Ukraine

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Related Publications (1)

• Burmester GR, Weinblatt ME, McInnes IB, Porter D, Barbarash O, Vatutin M, Szombati I, Esfandiari E, Sleeman MA, Kane CD, Cavet G, Wang B, Godwood A, Magrini F; EARTH Study Group. Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. Ann Rheum Dis. 2013 Sep 1;72(9):1445-52. doi: 10.1136/annrheumdis-2012-202450. Epub 2012 Dec 12.

  PMID: 23234647 BACKGROUND

Related Links

• CAM-3001\_CP-219\_Redacted\_4Mar13

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

mavrilimumab

Condition Hierarchy (Ancestors)

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

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2010
• First Posted: January 18, 2010
• Study Start: January 5, 2010
• Primary Completion: June 9, 2011
• Study Completion: July 27, 2012
• Last Updated: June 25, 2018
• Results First Posted: February 16, 2017

Record last verified: 2018-03

Locations

RO (3); BU (3); ES (1); HU (3); LI (2); LA (3); RU (6); UA (3); PL (8); CZ (6); JP (17)