Clinical trial NCT01225393: A Study to Evaluate the Efficacy and Safety of MLTA3698A in Combination With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Compared With Adalimumab in Combination With a DMARD in Patients With Active Rheumatoid Arthritis
Official title: A Phase II, Randomized, Double-Blind, Parallel-Group Study to Evaluate the Efficacy and Safety of MLTA3698A in Combination With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Compared With Adalimumab in Combination With a DMARD in Patient With Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2010-10-21
Enrollment: 211
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase II, randomized, double-blind, placebo-controlled, parallel-group, multicenter study enrolling patients with active rheumatoid arthritis (RA).


Eligibility criteria: Inclusion Criteria:

* Diagnosis of RA according to the 1987 revised ACR Criteria for the Classification of RA for at least 6 months prior to screening
* Positive for rheumatoid factor or anti-cyclic citrullinated peptide (CCP) antibody, or both
* Active disease, defined as: CRP \>= 1.0 mg/dL; swollen joint count \>= 6 (66 joint count); tender joint count \>= 6 (68 joint count)
* Previous inadequate clinical response to at least one disease-modifying anti-rheumatic drug (DMARD) consisting of either methotrexate (MTX) or leflunomide (LFU)
* For patients currently receiving corticosteroids: Treatment at a stable dose during last 4 weeks prior to screening
* For patients currently receiving non-steroidal anti-inflammatory drugs (NSAIDs): Treatment at a stable dose during last 4 weeks prior to screening
* For patients currently receiving sulfasalazine or anti-malarials: Treatment initiated and continued for at least the last 6 months prior to screening and on a stable dose
* For patients of reproductive potential (males and females): Willing to use a highly effective birth control method for the duration of the study according to local guidelines

Exclusion Criteria:

* Pregnant, planning to become pregnant during the study, or breastfeeding
* Clinically significant abnormal laboratory values or abnormal ECG or vital signs
* History of anaphylactic reactions
* Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis, or Felty's syndrome), however patients with secondary Sjogren's syndrome are eligible for the study
* History of or current inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthritis, Lyme disease) or other systemic autoimmune disorder (e.g., systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease, or other overlap syndrome)
* Current or recent (within 4 weeks prior to screening) infection, including signs, symptoms or serology of any infection, including HIV, hepatitis B or C, tuberculosis
* Administration of a live, attenuated vaccine within 1 month before dosing or anticipation that such a live attenuated vaccine will be required during the study
* Previous treatment with anti-TNF biologics or other biologic agents, including anti-CD20-directed therapy (e.g. rituximab), anti-IL6-directed therapy (e.g. tocilizumab), or T cell-directed therapy (e.g. abatacept)

Primary outcomes:
measure: Baseline change in disease activity, assessed as the Disease Activity Score (DAS28) and erythrocyte sedimentation rate, or DAS28-(4)-ESR
timeFrame: Day 85
measure: Incidence and severity of adverse events and clinical laboratory abnormalities as a measure of safety and tolerability of MLTA3698A
timeFrame: Length of study (through Day 85)
Secondary outcomes:
measure: ACR20 response rate (the proportion of patients in each treatment group meeting the American College of Rheumatology 20% responder criteria [ACR20] for their average response )
timeFrame: Day 85
measure: ACR50 response rate (the proportion of patients in each treatment group meeting the American College of Rheumatology 50% responder criteria [ACR50] for their average response )
timeFrame: Day 85
measure: ACR70 response rate (the proportion of patients in each treatment group meeting the American College of Rheumatology 70% responder criteria [ACR70] for their average response)
timeFrame: Day 85
measure: Tender joint count
timeFrame: Day 85
measure: Swollen joint count
timeFrame: Day 85
measure: Investigator Global Assessment of Disease Activity
timeFrame: Day 85
measure: Patient Global Assessment of Pain and Disease Activity
timeFrame: Day 85
measure: Health Assessment Questionnaire Disability Index
timeFrame: Day 85
measure: Patient's Global Health or Short Form Health Survey (SF-36)
timeFrame: Day 85
measure: European League Against Rheumatism response rate
timeFrame: Day 85
measure: Serum C-reactive protein levels
timeFrame: Day 85
measure: Erythrocyte sedimentation rate
timeFrame: Day 85
Other outcomes:
Locations:
city: Anniston
country: United States
state: Alabama
city: Birmingham
country: United States
state: Alabama
city: Peoria
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Upland
country: United States
state: California
city: Ormond Beach
country: United States
state: Florida
city: Lexington
country: United States
state: Kentucky
city: Kalamazoo
country: United States
state: Michigan
city: Flowood
country: United States
state: Mississippi
city: Reno
country: United States
state: Nevada
city: Charleston
country: United States
state: South Carolina
city: San Antonio
country: United States
state: Texas
city: Chesapeake
country: United States
state: Virginia
city: Clarksburg
country: United States
state: West Virginia
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Santiago
country: Chile
city: Santiago
country: Chile
city: Santiago
country: Chile
city: Bad Nauheim
country: Germany
city: Berlin
country: Germany
city: Erfurt
country: Germany
city: Freiburg
country: Germany
city: Herne
country: Germany
city: Kiel
country: Germany
city: Köln
country: Germany
city: Zerbst
country: Germany
city: Bekescsaba
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Veszprem
country: Hungary
city: Culiacan
country: Mexico
city: Guadalajara
country: Mexico
city: Guadalajara
country: Mexico
city: Guadalajara
country: Mexico
city: Leon
country: Mexico
city: Merida
country: Mexico
city: Mexicali
country: Mexico
city: Mexico City
country: Mexico
city: Mexico
country: Mexico
city: Monterrey, NL
country: Mexico
city: Lima
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: San Isidro
country: Peru
city: San Isidro
country: Peru
city: Bialystok
country: Poland
city: Bialystok
country: Poland
city: Elblag
country: Poland
city: Koscian
country: Poland
city: Krakow
country: Poland
city: Lublin
country: Poland
city: Warszawa
country: Poland
city: Baia Mare
country: Romania
city: Bucharest
country: Romania
city: Bucharest
country: Romania
city: Cluj-Napoca
country: Romania
city: Galati
country: Romania
city: Torrelavega
country: Spain
state: Cantabria
city: A Coruna
country: Spain
state: La Coruña
city: Seville
country: Spain
state: Sevilla
city: S. Cristobal de la Laguna
country: Spain
state: Tenerife
Study officials:
affiliation: Genentech, Inc.
name: John C. Davis, Jr., M.D., M.P.H.
role: STUDY_DIRECTOR
References:
citation: Kennedy WP, Simon JA, Offutt C, Horn P, Herman A, Townsend MJ, Tang MT, Grogan JL, Hsieh F, Davis JC. Efficacy and safety of pateclizumab (anti-lymphotoxin-alpha) compared to adalimumab in rheumatoid arthritis: a head-to-head phase 2 randomized controlled study (The ALTARA Study). Arthritis Res Ther. 2014 Oct 30;16(5):467. doi: 10.1186/s13075-014-0467-3.