Clinical trial NCT00902486: INCB028050 Compared to Background Therapy in Patients With Active Rheumatoid Arthritis (RA) With Inadequate Response to Disease Modifying Anti-Rheumatic Drugs
Official title: A Randomized, Double-blind, Placebo Controlled, Dose Ranging, Parallel Group, Phase 2 Study of INCB028050 Compared to Background Therapy in Patients With Active RA With Inadequate Response to Any Disease Modifying Anti-Rheumatic Drugs (DMARD) Therapy Including Biologics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2009-05-15
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a randomized, double blind, placebo controlled, dose ranging, parallel group study. Participants who had active rheumatoid arthritis (RA) who had inadequate response to any disease modifying anti-rheumatic drug (DMARD) therapy including biologics were enrolled. Screening evaluations were performed within approximately 28 days of randomization. The duration of the study was 6 months with the primary endpoint assessed at 3 months. Eligible participants were randomly assigned to one of three doses (4, 7 or 10 mg QD) of INCB028050 (Baricitinib) or placebo.


Eligibility criteria: Inclusion Criteria:

* Must have rheumatoid arthritis which has been inadequately controlled with at least one DMARD
* For subjects receiving antimalarials, they must be treated with antimalarials for at least 6 months and receiving a stable daily dose
* For subjects receiving sulfasalazine, they must be treated with Sulfasalazine (SSZ) for at least 6 months and receiving a stable daily dose of no more than 3 grams per day
* For subjects on methotrexate, they must be treated with methotrexate for at least 6 months, and receiving a stable weekly dose of methotrexate between 7.5 and 25 mg
* For subjects on leflunomide, they must be treated with leflunomide for at least 6 months, and receiving a stable dose of leflunomide between 10 to 20 mg
* For subjects receiving corticosteroids, they must be on a dose not to exceed 10 mg of prednisone daily
* Active rheumatoid arthritis at the time of screening defined by the following: 6 or more joints tender or painful on motion and 4 or more swollen joints and at least one of the following two: Erythrocyte sedimentation rate (ESR) greater than or equal to 28 mm/hr or C-reactive protein (CRP) greater than or equal to 7 mg/liter
* Have evidence of lack of risk for tuberculosis

Exclusion Criteria:

* Current or recent viral, bacterial, fungal, parasitic or mycobacterial infection requiring systemic therapy
* History of infected joint prosthesis
* Subjects who have a current or recent history of severe, progressive, uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological or cerebral disease
* Subjects who have received treatment with the following drugs or drug classes within the specified timeframe: prior treatment with rituximab within 12 months, prior treatment with an oral Janus kinase (JAK) inhibitor, DMARDs or other anti-rheumatic therapies not specified and allowed according to protocol, treatment with any investigational medication within 12 weeks or 5 half-lives (whichever is longer), and treatment with a biologic agent within 12 weeks prior to the first dose of study medication
* Subjects with a past history of neutropenia, thrombocytopenia or anemia requiring transfusion other than at the time of trauma or surgery, and subjects that meet protocol specified laboratory measures

Primary outcomes:
measure: The Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Improvement
timeFrame: Week 12
measure: Participants With at Least 1 Adverse Event From Baseline Through Week 12
timeFrame: From Baseline through week 12
Secondary outcomes:
measure: Participants With at Least 1 Adverse Event From Week 12 to Week 24
timeFrame: Week 12 to Week 24
measure: The Percentage of Participants Who Were Assigned to Active Treatment at Baseline Achieving ACR 20 Improvement at Week 24
timeFrame: From Baseline to Week 24
measure: The Percentage of Participants Achieving American College of Rheumatology (ACR) 50 Improvement at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: The Percentage of Participants Achieving American College of Rheumatology (ACR) 70 Improvement at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: The Percentage of Participants Achieving American College of Rheumatology (ACR) 90 Improvement at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: Change in Disease Activity Score 28 (DAS28) CRP Score From Baseline at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change in Disease Activity Score 28 (DAS28) ESR Score From Baseline at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Percentage of Participants Achieving Low Disease Activity by DAS28 (ESR)≤3.2
timeFrame: Week 12 and Week 24
measure: Percentage of Participants Achieving Remission by DAS28 (ESR) ≤2.6
timeFrame: Week 12 and Week 24
measure: Percentage of Participants Achieving Remission by DAS28 (CRP) ≤2.6
timeFrame: Week 12 and Week 24
measure: Change in ACR Assessment Tender Joint Count (TJC) From Baseline to Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change in ACR Assessment Swollen Joint Count (SJC) From Baseline to Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change in Participants' Assessment of Pain From Baseline at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change in Participants' Global Assessment of Disease Activity From Baseline at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change in Physician's Global Assessment of Disease Activity (PGA) From Baseline at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change in Erythrocyte Sedimentation Rate (ESR) From Baseline at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change in C-reactive Protein (CRP) From Baseline at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change in Duration of Morning Stiffness From Baseline at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Percentage of Participants Achieving Good European League Against Rheumatism (EULAR) Response (DAS28 ESR) at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving Good EULAR Response (DAS28ESR) at Week 24
timeFrame: Week 24
measure: Percentage of Participants Achieving Good EULAR Response (DAS28CRP) at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving Good EULAR Response (DAS28CRP) at Week 24
timeFrame: Week 24
measure: Change in SF-36 Mental Component Summary From Baseline at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change in SF-36 Physical Component Summary From Baseline at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Percent of Participants Achieving a Minimum Clinically Important Difference (MCID) in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: Percent of Participants Achieving a MCID in the Pain Score (Participant's Assessment of Pain) at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: Percent of Participants Achieving a MCID in the SF-36 Physical Components and Mental Components at Week 12 and Week 24
timeFrame: Week 12 and Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Paradise Valley
country: United States
state: Arizona
city: Peoria
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Palm Desert
country: United States
state: California
city: Santa Maria
country: United States
state: California
city: Santa Monica
country: United States
state: California
city: Westlake Village
country: United States
state: California
city: Whittier
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Aventura
country: United States
state: Florida
city: Daytona Beach
country: United States
state: Florida
city: Gainesville
country: United States
state: Florida
city: Lake Mary
country: United States
state: Florida
city: Naples
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Springfield
country: United States
state: Illinois
city: South Bend
country: United States
state: Indiana
city: Wichita
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: Frederick
country: United States
state: Maryland
city: Wheaton
country: United States
state: Maryland
city: Saint Louis
country: United States
state: Missouri
city: Lincoln
country: United States
state: Nebraska
city: Reno
country: United States
state: Nevada
city: Freehold
country: United States
state: New Jersey
city: Lake Success
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Hickory
country: United States
state: North Carolina
city: Middleburg Heights
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Duncansville
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Sellersville
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Arlington
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Brno
country: Czechia
city: Ceska Lipa
country: Czechia
city: Chomutov
country: Czechia
city: Hlucin
country: Czechia
city: Hustopece
country: Czechia
city: Kromeriz
country: Czechia
city: Praha
country: Czechia
city: Zlin
country: Czechia
Study officials:
References:
citation: Taylor PC, Takeuchi T, Burmester GR, Durez P, Smolen JS, Deberdt W, Issa M, Terres JR, Bello N, Winthrop KL. Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database. Ann Rheum Dis. 2022 Mar;81(3):335-343. doi: 10.1136/annrheumdis-2021-221276. Epub 2021 Oct 27.
citation: Combe B, Balsa A, Sarzi-Puttini P, Tony HP, de la Torre I, Rogai V, Durand F, Witt S, Zhong J, Dougados M. Efficacy and safety data based on historical or pre-existing conditions at baseline for patients with active rheumatoid arthritis who were treated with baricitinib. Ann Rheum Dis. 2019 Aug;78(8):1135-1138. doi: 10.1136/annrheumdis-2018-214261. Epub 2019 Mar 6. No abstract available.
citation: Taylor PC, Kremer JM, Emery P, Zuckerman SH, Ruotolo G, Zhong J, Chen L, Witt S, Saifan C, Kurzawa M, Otvos JD, Connelly MA, Macias WL, Schlichting DE, Rooney TP, de Bono S, McInnes IB. Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies. Ann Rheum Dis. 2018 Jul;77(7):988-995. doi: 10.1136/annrheumdis-2017-212461. Epub 2018 Feb 20.