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

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

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

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: placebo; Drug: MLTA3698A; Drug: leflunomide; Drug: methotrexate; Drug: adalimumab

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1233
  • Sofia, Bulgaria, 1407
  • Sofia, Bulgaria, 1505
• Chile
  • Santiago, Chile, 00000
  • Santiago, Chile, 7501126
  • Santiago, Chile, 7510186
• Germany
  • Bad Nauheim, Germany, 61231
  • Berlin, Germany, 14059
  • Erfurt, Germany, 99096
  • Freiburg, Germany, 79106
  • Herne, Germany, 44649
  • Kiel, Germany, 24105
  • Köln, Germany, 50924
  • Zerbst, Germany, 39261
• Hungary
  • Bekescsaba, Hungary, 5600
  • Budapest, Hungary, 1036
  • Budapest, Hungary, 1027
  • Debrecen, Hungary, 4032
  • Veszprem, Hungary, H-8200
• Mexico
  • Culiacan, Mexico, 80000
  • Guadalajara, Mexico, 44340
  • Guadalajara, Mexico, 44600
  • Guadalajara, Mexico, 44690
  • Leon, Mexico, 37320
  • Merida, Mexico, 97000
  • Mexicali, Mexico, 21100
  • Mexico, Mexico, 44620
  • Mexico City, Mexico, 06700
  • Monterrey, NL, Mexico, 64000
• Peru
  • Lima, Peru, 41
  • Lima, Peru, Lima 27
  • Lima, Peru, Lima 1
  • Lima, Peru, Lima 25
  • Lima, Peru, LIMA 34
  • Lima, Peru, Lima 41
  • San Isidro, Peru, Lima 27
  • San Isidro, Peru, L27 Lima
• Poland
  • Bialystok, Poland, 15-099
  • Bialystok, Poland, 15-461
  • Elblag, Poland, 82-300
  • Koscian, Poland, 64-000
  • Krakow, Poland, 30-510
  • Lublin, Poland, 20-607
  • Warszawa, Poland, 02-653
• Romania
  • Baia Mare, Romania, 430031
  • Bucharest, Romania, 011172
  • Bucharest, Romania, 010584
  • Cluj-Napoca, Romania, 400006
  • Galati, Romania, 800578
• Spain
  • Cantabria
    • Torrelavega, Cantabria, Spain, 39300
  • La Coruña
    • A Coruna, La Coruña, Spain, 15006
  • Sevilla
    • Seville, Sevilla, Spain, 41071
  • Tenerife
    • S. Cristobal de la Laguna, Tenerife, Spain, 38320
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
    • Birmingham, Alabama, United States, 35216
  • Arizona
    • Peoria, Arizona, United States, 85381
  • California
    • Los Angeles, California, United States, 90033
    • Upland, California, United States, 91786
  • Florida
    • Ormond Beach, Florida, United States, 32174
  • Kentucky
    • Lexington, Kentucky, United States, 40515
  • Michigan
    • Kalamazoo, Michigan, United States, 49009
  • Mississippi
    • Flowood, Mississippi, United States, 39232
  • Nevada
    • Reno, Nevada, United States, 89502
  • South Carolina
    • Charleston, South Carolina, United States, 29406
  • Texas
    • San Antonio, Texas, United States, 78217
  • Virginia
    • Chesapeake, Virginia, United States, 23320
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: B	Drug: placebo; Subcutaneous repeating dose; Drug: leflunomide; Stable dose if not on methotrexate; Drug: methotrexate; Stable dose if not on leflunomide; Drug: adalimumab; Subcutaneous repeating dose
Placebo Comparator: C	Drug: placebo; Subcutaneous repeating dose; Drug: leflunomide; Stable dose if not on methotrexate; Drug: methotrexate; Stable dose if not on leflunomide
Experimental: A	Drug: MLTA3698A; Subcutaneous repeating dose; Drug: leflunomide; Stable dose if not on methotrexate; Drug: methotrexate; Stable dose if not on leflunomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Baseline change in disease activity, assessed as the Disease Activity Score (DAS28) and erythrocyte sedimentation rate, or DAS28-(4)-ESR	Day 85
Incidence and severity of adverse events and clinical laboratory abnormalities as a measure of safety and tolerability of MLTA3698A	Length of study (through Day 85)

Secondary Outcome Measures

Outcome Measure	Time Frame
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 )	Day 85
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 )	Day 85
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)	Day 85
Tender joint count	Day 85
Swollen joint count	Day 85
Investigator Global Assessment of Disease Activity	Day 85
Patient Global Assessment of Pain and Disease Activity	Day 85
Health Assessment Questionnaire Disability Index	Day 85
Patient's Global Health or Short Form Health Survey (SF-36)	Day 85
European League Against Rheumatism response rate	Day 85
Serum C-reactive protein levels	Day 85
Erythrocyte sedimentation rate	Day 85

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: John C. Davis, Jr., M.D., M.P.H., Genentech, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: October 18, 2010
• First Submitted That Met QC Criteria: October 19, 2010
• First Posted (Estimate): October 21, 2010

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Adalimumab; Methotrexate; Leflunomide
• Other Study ID Numbers: ALT4864g; GA00932 (Other Identifier: Hoffmann-La Roche)