A Study of ARRY-438162 in Patients With Rheumatoid Arthritis

Phase 2

Completed

Conditions: Rheumatoid Arthritis

Interventions: Drug: ARRY-438162, MEK inhibitor; oral
Drug: Placebo; oral

Registration Number: NCT00650767

Lead Sponsor: Array Biopharma, now a wholly owned subsidiary of Pfizer

Brief Summary: This is a Phase 2 study, involving a 12-week treatment period, designed to evaluate the effectiveness of investigational study drug ARRY-438162 in treating rheumatoid arthritis in patients on stable doses of methotrexate, and to further evaluate the safety of the study drug. Approximately 200 patients from the US, Argentina, Brazil, Hungary, Peru, Poland and Romania will be enrolled in this study.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 201

Inclusion Criteria

Diagnosis of rheumatoid arthritis, based on the American College of Rheumatology (ACR) 1987 Revised Criteria, prior to first dose of study drug.
Patient has received a stable dose of methotrexate for ≥ 6 weeks prior to first dose of study drug and is willing to continue on this regimen for the duration of the study.
Patient has received a stable dose of folate for ≥ 6 weeks and is willing to continue on this regimen for the duration of the study.
No prior use of biological agents for the treatment of rheumatoid arthritis.
Additional criteria exist.

Key

Exclusion Criteria

Diagnosis of any other inflammatory or non-inflammatory arthritis that may interfere with disease activity assessments or clinically apparent osteoarthritis which would affect subsequent efficacy measures.
A history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological disease or severe systemic involvement with rheumatoid arthritis.
Additional criteria exist.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ARRY-438162 (Schedule 2)	ARRY-438162, MEK inhibitor; oral	-
ARRY-438162 (Schedule 3)	ARRY-438162, MEK inhibitor; oral	-
ARRY-438162 (Schedule 1)	ARRY-438162, MEK inhibitor; oral	-
Placebo	Placebo; oral	-

Primary Outcome Measures

Name	Time	Method
American College of Rheumatology 20% (ACR20) Response Rate at Week 12	Week 12	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 20 has a positive outcome if 20% improvement in tender or swollen joint counts were achieved as well as a 20% improvement in at least three of the other five criteria.

Secondary Outcome Measures

Name	Time	Method
C-Reactive Protein (CRP) at Week 12	Week 12
American College of Rheumatology 50% (ACR50) Response Rate at Week 8	Week 8	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 50 has a positive outcome if 50% improvement in tender or swollen joint counts were achieved as well as a 50% improvement in at least three of the other five criteria.
American College of Rheumatology 70% (ACR70) Response Rate at Week 1	Week 1	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 70 has a positive outcome if 70% improvement in tender or swollen joint counts were achieved as well as a 70% improvement in at least three of the other five criteria.
American College of Rheumatology 70% (ACR70) Response Rate at Week 2	Week 2	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 70 has a positive outcome if 70% improvement in tender or swollen joint counts were achieved as well as a 70% improvement in at least three of the other five criteria.
American College of Rheumatology 70% (ACR70) Response Rate at Week 16 (Follow-up)	Week 16 (Follow-up)	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 70 has a positive outcome if 70% improvement in tender or swollen joint counts were achieved as well as a 70% improvement in at least three of the other five criteria.
American College of Rheumatology 20% (ACR20) Response Rate at Week 2	Week 2	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 20 has a positive outcome if 20% improvement in tender or swollen joint counts were achieved as well as a 20% improvement in at least three of the other five criteria.
American College of Rheumatology 20% (ACR20) Response Rate at Week 1	Week 1	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 20 has a positive outcome if 20% improvement in tender or swollen joint counts were achieved as well as a 20% improvement in at least three of the other five criteria.
American College of Rheumatology 20% (ACR20) Response Rate at Week 16 (Follow-up)	Week 16 (Follow-up)	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 20 has a positive outcome if 20% improvement in tender or swollen joint counts were achieved as well as a 20% improvement in at least three of the other five criteria.
American College of Rheumatology 50% (ACR50) Response Rate at Week 1	Week 1	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 50 has a positive outcome if 50% improvement in tender or swollen joint counts were achieved as well as a 50% improvement in at least three of the other five criteria.
C-Reactive Protein (CRP) at Week 2	Week 2
American College of Rheumatology 20% (ACR20) Response Rate at Week 4	Week 4	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 20 has a positive outcome if 20% improvement in tender or swollen joint counts were achieved as well as a 20% improvement in at least three of the other five criteria.
American College of Rheumatology 20% (ACR20) Response Rate at Week 8	Week 8	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 20 has a positive outcome if 20% improvement in tender or swollen joint counts were achieved as well as a 20% improvement in at least three of the other five criteria.
American College of Rheumatology 50% (ACR50) Response Rate at Week 2	Week 2	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 50 has a positive outcome if 50% improvement in tender or swollen joint counts were achieved as well as a 50% improvement in at least three of the other five criteria.
American College of Rheumatology 50% (ACR50) Response Rate at Week 4	Week 4	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 50 has a positive outcome if 50% improvement in tender or swollen joint counts were achieved as well as a 50% improvement in at least three of the other five criteria.
American College of Rheumatology 50% (ACR50) Response Rate at Week 12	Week 12	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 50 has a positive outcome if 50% improvement in tender or swollen joint counts were achieved as well as a 50% improvement in at least three of the other five criteria.
American College of Rheumatology 70% (ACR70) Response Rate at Week 8	Week 8	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 70 has a positive outcome if 70% improvement in tender or swollen joint counts were achieved as well as a 70% improvement in at least three of the other five criteria.
American College of Rheumatology (ACR) Response Criteria - Swollen Joint Count (28)	Week 16 (Follow-up)	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The swollen joint count was calculated based on the swelling response of 28 joints. Possible values ranged from 0 to 28. A lower score indicated less joint swelling.
American College of Rheumatology 70% (ACR70) Response Rate at Week 12	Week 12	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 70 has a positive outcome if 70% improvement in tender or swollen joint counts were achieved as well as a 70% improvement in at least three of the other five criteria.
Patient's Assessment of Arthritis Pain - Visual Analog Scale (VAS)	Week 16 (Follow-up)	The Patient's Assessment of Pain utilized a 0 to 100 mm visual analog scale, 0 being no pain and 100 being most severe pain.
Patient's Global Assessment of Arthritis - Visual Analog Score (VAS)	Week 16 (Follow-up)	The Patient's Global Assessment of Arthritis was an evaluation based on the patient's disease signs, functional capacity and physical examination, and was independent of the Physician's Global Assessment of Arthritis. The patient self-assessed how the arthritis affected their lives at the time of the visit using the visual analog scale (VAS). Patients answered the following: "Considering all the ways in which illness and health conditions may affect you at this time, please make a mark below to show how you are doing." The patient's response was recorded using the 100 mm visual analog scale between 0 (Very Well) and 100 (Very Poorly).
American College of Rheumatology 50% (ACR50) Response Rate at Week 16 (Follow-up)	Week 16 (Follow-up)	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 50 has a positive outcome if 50% improvement in tender or swollen joint counts were achieved as well as a 50% improvement in at least three of the other five criteria.
Health Assessment Questionnaire - Disability Index (HAQ-DI)	Week 16 (Follow-up)	The HAQ-DI contains a list of items that assessed the degree of difficulty experienced in 8 categories of daily living activities (included in 20 questions) over the past week: Dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each activity category consists of 2 or 3 items. For each question in the HAQ-DI, the level of difficulty was scored from 0 to 3 with 0 equal to "without difficulty," 1 equal to "with some difficulty," 2 equal to "with much difficulty" and 3 equal to "unable to do." Any activity that required assistance from another individual or required the use of an assistive device adjusted to a minimum score of 2 to represent a more limited functional status. The HAQ-DI score takes values between 0 and 3, with a higher score indicating greater disability.
C-Reactive Protein (CRP) at Baseline	Baseline
C-Reactive Protein (CRP) at Week 4	Week 4
SF-36 Health Questionnaire - Version 2 (SF-36v2) - Physical Functioning	Week 16 (Follow-up)	The SF-36v2 (Acute version) is a 36-item generic health status measure that yields an 8-scale profile of functional health and well-being as well as psychometrically-based physical and mental health summary measures. The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability, while the higher the score the less disability.
American College of Rheumatology 70% (ACR70) Response Rate at Week 4	Week 4	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. The ACR 70 has a positive outcome if 70% improvement in tender or swollen joint counts were achieved as well as a 70% improvement in at least three of the other five criteria.
Physician's Global Assessment of Arthritis - Visual Analog Score (VAS)	Week 16 (Follow-up)	The Physician's Global Assessment of Arthritis was an evaluation based on the patient's disease signs, functional capacity and physical examination, and was independent of the Patient's Global Assessment of Arthritis. The Investigator assessed how the overall arthritis appeared at the time of the visit using the visual analog scale (VAS). The physician's response was recorded using the 100 mm visual analog scale between 0 (Very Good) and 100 (Very Bad).
C-Reactive Protein (CRP) at Week 16 (Follow-up)	Week 16 (Follow-up)
SF-36 Health Questionnaire - Version 2 (SF-36v2) - Bodily Pain	Week 16 (Follow-up)	The SF-36v2 (Acute version) is a 36-item generic health status measure that yields an 8-scale profile of functional health and well-being as well as psychometrically-based physical and mental health summary measures. The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability, while the higher the score the less disability.
SF-36 Health Questionnaire - Version 2 (SF-36v2) - Mental Health Component Score	Week 16 (Follow-up)	The SF-36v2 (Acute version) is a 36-item generic health status measure that yields an 8-scale profile of functional health and well-being as well as psychometrically-based physical and mental health summary measures. The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability, while the higher the score the less disability. Additionally, two summary scale scores can be calculated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Summary statistics were calculated for each of the 8 scales, the 2 summary measures, and changes from baseline for each treatment group.
American College of Rheumatology (ACR) Response Criteria - Tender Joint Count (28)	Week 16 (Follow-up)	The ACR (American College of Rheumatology) Criteria is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for Rheumatoid Arthritis. Tender joint count is calculated based on the tenderness response of 28 joints. Possible values ranged from 0 to 28. A lower score indicated less joint tenderness.
C-Reactive Protein (CRP) at Week 8	Week 8
Disease Activity Score (DAS) Using C-Reactive Protein (DAS28-4[CRP])	Week 16 (Follow-up)	The DAS28-4(CRP) score is a measure of the subject's disease activity. DAS28-4(CRP) is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity and CRP. DAS28 provides a number on a scale (0 to 10) indicating current disease activity. A score above 5.1 means high disease activity and a score below 3.2 indicates low disease activity.
SF-36 Health Questionnaire - Version 2 (SF-36v2) - Role-Physical	Week 16 (Follow-up)	The SF-36v2 (Acute version) is a 36-item generic health status measure that yields an 8-scale profile of functional health and well-being as well as psychometrically-based physical and mental health summary measures. The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability, while the higher the score the less disability.
SF-36 Health Questionnaire - Version 2 (SF-36v2) - General Health	Week 16 (Follow-up)	The SF-36v2 (Acute version) is a 36-item generic health status measure that yields an 8-scale profile of functional health and well-being as well as psychometrically-based physical and mental health summary measures. The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability, while the higher the score the less disability.
SF-36 Health Questionnaire - Version 2 (SF-36v2) - Vitality	Week 16 (Follow-up)	The SF-36v2 (Acute version) is a 36-item generic health status measure that yields an 8-scale profile of functional health and well-being as well as psychometrically-based physical and mental health summary measures. The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability, while the higher the score the less disability.
SF-36 Health Questionnaire - Version 2 (SF-36v2) - Social Functioning	Week 16 (Follow-up)	The SF-36v2 (Acute version) is a 36-item generic health status measure that yields an 8-scale profile of functional health and well-being as well as psychometrically-based physical and mental health summary measures. The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability, while the higher the score the less disability.
SF-36 Health Questionnaire - Version 2 (SF-36v2) - Mental Health	Week 16 (Follow-up)	The SF-36v2 (Acute version) is a 36-item generic health status measure that yields an 8-scale profile of functional health and well-being as well as psychometrically-based physical and mental health summary measures. The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability, while the higher the score the less disability.
SF-36 Health Questionnaire - Version 2 (SF-36v2) - Role-Emotional	Week 16 (Follow-up)	The SF-36v2 (Acute version) is a 36-item generic health status measure that yields an 8-scale profile of functional health and well-being as well as psychometrically-based physical and mental health summary measures. The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability, while the higher the score the less disability.
SF-36 Health Questionnaire - Version 2 (SF-36v2) - Physical Component Score	Week 16 (Follow-up)	The SF-36v2 (Acute version) is a 36-item generic health status measure that yields an 8-scale profile of functional health and well-being as well as psychometrically-based physical and mental health summary measures. The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability, while the higher the score the less disability. Additionally, two summary scale scores can be calculated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Summary statistics were calculated for each of the 8 scales, the 2 summary measures, and changes from baseline for each treatment group.
C-Reactive Protein (CRP) at Week 1	Week 1

Trial Locations

Locations (33): CER San Juan
🇦🇷
San Juan, Argentina
Hospital São Paulo / Instituto Paulista de Reumatologia
🇧🇷
São Paulo, SP, Brazil
Hospital Heliópolis
🇧🇷
São Paulo, SP, Brazil
Budai Irgalmasrendi Kórház - Allergólógia és Immunológia
🇭🇺
Budapest, Hungary
Mozgasszervi Rehabilitacios Kozpont
🇭🇺
Mezőkövesd, Hungary
Clínica Ricardo Palma- Sitio de Investigacion de Reumatologia
🇵🇪
Lima, Peru
Centrum Osteoporozy i Chorób Kostno-Stawowych
🇵🇱
Bialystok, Poland
Hospital Maria Auxiliadora - Centro de Investigaciones Medicas
🇵🇪
Lima, Peru
Wojewódzki Szpital Zespolony - Oddział Reumatologiczny
🇵🇱
Elblag, Poland
NZOZ Reumed
🇵🇱
Lublin, Poland
Centrum Leczenia Chorob Cywilizacyjnych
🇵🇱
Warszawa, Poland
Cabinet Medical "Prof. Dr. Miorara Banciu"
🇷🇴
Timisoara, Romania
Spitalul Clinic Judetean de Urgenta
🇷🇴
Targu Mures, Romania
Médicos Unidos Ltda.
🇧🇷
Goiânia, GO, Brazil
Spartanburg Medical Research
🇺🇸
Spartanburg, South Carolina, United States
Asistencia Integral en Reumatologia
🇦🇷
Buenos Aires, Argentina
CEMIC
🇦🇷
Buenos Aires, Argentina
Centro Medico Privado de Reumatologia
🇦🇷
San Miguel de Tucumán, Argentina
Hospital de Clínicas de Porto Alegre
🇧🇷
Porto Alegre, RS, Brazil
Hospital São Lucas da da Pontifícia Universidade Católica do Rio Grande do Sul
🇧🇷
Porto Alegre, RS, Brazil
Instituto de Medicina Avançada (IMA Brasil)
🇧🇷
São Paulo, SP, Brazil
Békés Megyei Pándy Kálmán Kórház - Rheumatology
🇭🇺
Gyula, Hungary
MÁV Kórház - Clinical Pharmacology
🇭🇺
Szolnok, Hungary
Spitalul Clinic "Sf, Maria"
🇷🇴
Bucuresti, Romania
Hospital Britanico
🇦🇷
Buenos Aires, Argentina
Centro de Investigaciones Clinicas del Litoral SRL
🇦🇷
Santa Fe, Argentina
CETI - Hospital das Clínicas da Universidade Federal do Paraná
🇧🇷
Curitiba, PR, Brazil
Synexus Ltd Hungary
🇭🇺
Budapest, Hungary
Clinica San Felipe - Centro de Estudios Clinicos CGYM
🇵🇪
Lima, Peru
Vas Megyei Markusovszky Korhaz Lajos Általános, Rehabilitációs és Gyógyfürdő Kórház, Egyetemi Oktató Kórház, Zártkörűen Működő Nonprofit Részvénytársaság - Rheumatology
🇭🇺
Szombathely, Hungary
Fejér Megyei Szent György Kórház - Rheumatology
🇭🇺
Székesfehérvár, Hungary
Instituto de Investigacion y Seguridad Medica EIRL
🇵🇪
Arequipa, Peru
Synexus SCM Sp. z o.o.
🇵🇱
Wroclaw, Poland