Clinical trial NCT01050998: A Study to Evaluate the Efficacy and Safety of CAM-3001 (Drug) in Subjects With Rheumatoid Arthritis
Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Efficacy and Safety of CAM-3001 in Subjects With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Mavrilimumab
CAM-3001
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
Collaborators: name: MedImmune Ltd
First posted: 2010-01-18
Enrollment: 516
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 assess the safety, tolerability and efficacy of multiple doses of the mavrilimumab (CAM-3001) administered subcutaneously in subjects with moderately active Rheumatoid Arthritis (RA).

Detailed description: This is a Phase 2, randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the efficacy and safety of multiple doses of the mavrilimumab (CAM-3001) (10 milligram \[mg\], 30 mg, 50 mg, and 100 mg) administered subcutaneously in adult subjects with moderately active RA.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85
timeFrame: Day 85
measure: Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85 by Region
timeFrame: Day 85
measure: Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85
timeFrame: Day 85
measure: Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85 by Region
timeFrame: Day 85
measure: Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85
timeFrame: Day 85
measure: Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region
timeFrame: Day 85
measure: Percentage of Participants Who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85
timeFrame: Day 85
measure: Percentage of Participants Who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region
timeFrame: Day 85
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: Baseline up to Day 169 (follow-up)
measure: Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Day 169 (follow-up)
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Results
timeFrame: Baseline up to Day 169 (follow-up)
measure: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85
timeFrame: Day 85
measure: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 by Region
timeFrame: Day 85
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85
timeFrame: Baseline and Day 85
measure: Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85
timeFrame: Day 85
measure: Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 by Region
timeFrame: Day 85
measure: Change From Baseline in Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85
timeFrame: Baseline and Day 85
measure: Dyspnea Score at Day 85
timeFrame: Day 85
measure: Change From Baseline in Dyspnea Score at Day 85
timeFrame: Baseline and Day 85
measure: Categorized Dyspnea Score at Day 85
timeFrame: Day 85
measure: Oxygen Saturation Level at Day 85
timeFrame: Day 85
measure: Oxygen Saturation Level at Day 85 by Region
timeFrame: Day 85
measure: Change From Baseline in Oxygen Saturation Level at Day 85
timeFrame: Baseline and Day 85
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Day 169 (follow-up)
Secondary outcomes:
measure: Change From Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85
timeFrame: Baseline and Day 85
measure: Change From Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85 by Region
timeFrame: Baseline and Day 85
measure: Percentage of Participants Who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85
timeFrame: Day 85
measure: Percentage of Participants Who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85 by Region
timeFrame: Day 85
measure: Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission
timeFrame: Baseline up to Day 169 (follow-up)
measure: Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission by Region
timeFrame: Baseline up to Day 169 (follow-up)
measure: Duration of DAS28 (CRP) and DAS28 (ESR) Response and Remission
timeFrame: Baseline up to Day 169
measure: Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85
timeFrame: Day 85
measure: Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85 by Region
timeFrame: Day 85
measure: Number of Participants Who Achieved ACR Categorical Responses
timeFrame: Day 85
measure: Continuous ACR (ACRn) Score
timeFrame: Day 85
measure: Continuous ACR (ACRn) Score by Region
timeFrame: Day 85
measure: Swollen and Tender Joint Count
timeFrame: Day 85
measure: Swollen and Tender Joint Count by Region
timeFrame: Day 85
measure: Physician Global Assessment of Disease Activity Score
timeFrame: Day 85
measure: Physician Global Assessment of Disease Activity Score by Region
timeFrame: Day 85
measure: Patient Global Assessment of Disease Activity Score
timeFrame: Day 85
measure: Patient Global Assessment of Disease Activity Score by Region
timeFrame: Day 85
measure: Patient Pain Assessment Score
timeFrame: Day 85
measure: Patient Pain Assessment Score by Region
timeFrame: Day 85
measure: Health Assessments Questionnaire-Disability Index (HAQ-DI) Score
timeFrame: Day 85
measure: Health Assessments Questionnaire-Disability Index (HAQ-DI) Score by Region
timeFrame: Day 85
measure: Health Assessments Questionnaire (HAQ) Pain Score
timeFrame: Day 85
measure: Health Assessments Questionnaire (HAQ) Pain Score by Region
timeFrame: Day 85
measure: Serum Concentration of C-Reactive Protein (CRP)
timeFrame: Day 85
measure: Serum Concentration of C-Reactive Protein (CRP) by Region
timeFrame: Day 85
measure: Serum Concentration of Erythrocyte Sedimentation Rate (ESR)
timeFrame: Day 85
measure: Serum Concentration of Erythrocyte Sedimentation Rate (ESR) by Region
timeFrame: Day 85
measure: Serum Concentration of Rheumatoid Factor (RF)
timeFrame: Day 85
measure: Serum Concentration of Anti-Citrullinated-Peptide-Antibody (ACPA)
timeFrame: Day 85
measure: Number of Participants Who Had Additional Medications
timeFrame: Baseline up to Day 169
measure: Number of Participants With Change in Methotrexate (MTX) and Corticosteroid (CST) Dose
timeFrame: Baseline, Day 1 to 85, Day 86 to 169
measure: Maximum Observed Serum Concentration (Cmax) for Mavrilimumab After First Dose by Region
timeFrame: Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) for Mavrilimumab After First Dose by Region
timeFrame: Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Mavrilimumab After First Dose by Region
timeFrame: Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
measure: Maximum Observed Serum Concentration (Cmax) for Mavrilimumab After Last Dose by Region
timeFrame: Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) for Mavrilimumab After Last Dose by Region
timeFrame: Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Mavrilimumab After Last Dose by Region
timeFrame: Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
measure: Terminal Phase Elimination Half-Life (t1/2) for Mavrilimumab After Last Dose by Region
timeFrame: Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
measure: Accumulation Ratio for Mavrilimumab After Last Dose by Region
timeFrame: Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
measure: Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab at Any Visit
timeFrame: Day 1 up to Day 169
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Varna
country: Bulgaria
facility: Research Site
city: Bruntal
country: Czechia
facility: Research Site
city: Ostrava - Trebovice
country: Czechia
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Praha 4 - Nusle
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Uherske Hradiste
country: Czechia
facility: Research Site
city: Zlin
country: Czechia
facility: Research Site
city: Tallinn
country: Estonia
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Sopron
country: Hungary
facility: Research Site
city: Zalaegerszeg
country: Hungary
facility: Research Site
city: Chiba-shi
country: Japan
facility: Research Site
city: Chiyoda-ku
country: Japan
facility: Research Site
city: Fukui-shi
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Goshogawara-shi
country: Japan
facility: Research Site
city: Hamamatsu-shi
country: Japan
facility: Research Site
city: Iizuka-shi
country: Japan
facility: Research Site
city: Kagoshima-shi
country: Japan
facility: Research Site
city: Kasama-shi
country: Japan
facility: Research Site
city: Kitakyushu-shi
country: Japan
facility: Research Site
city: Nagano-Shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Okayama-shi
country: Japan
facility: Research Site
city: Omura-shi
country: Japan
facility: Research Site
city: Sagamihara-shi
country: Japan
facility: Research Site
city: Sasebo-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Liepaja
country: Latvia
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Valmiera
country: Latvia
facility: Research Site
city: Klaipeda
country: Lithuania
facility: Research Site
city: Vilnius
country: Lithuania
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Legnica
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Torun
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Ploiesti
country: Romania
facility: Research Site
city: Targu Mures
country: Romania
facility: Research Site
city: Barnaul
country: Russian Federation
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Kemerovo
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Donetsk
country: Ukraine
facility: Research Site
city: Kiev
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
Study officials:
affiliation: MedImmune Ltd
name: Marius Albulescu
role: STUDY_DIRECTOR
References:
citation: 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.