A Study of RO7123520 to Evaluate the Safety and Efficacy in Participants With Moderately To Severely Active Rheumatoid Arthritis (RA) Who Are Inadequately Responding to Anti-Tumor Necrosis Factor (TNF)-Alpha Therapy

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase II Study to Evaluate The Safety and Efficacy of RO7123520 as Adjunct Treatment in Patients With Moderately to Severely Active Rheumatoid Arthritis and an Inadequate Response to TNF-alpha Inhibitors

This is a Phase IIa/b double-blind, placebo-controlled, randomized, parallel group, multicenter study to evaluate the safety and efficacy of RO7123520 as adjunctive therapy in participants with RA who are inadequately responding to standard-of-care (methotrexate and anti-TNF-alpha therapy). Part 1 of the study will evaluate safety. Part 2 will evaluate efficacy and safety. Part 3 will evaluate dose-ranging efficacy. Participants will have the option of continuing to the extension period of the study.

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Anti-TNF-alpha; Drug: Methotrexate; Drug: Placebo; Drug: RO7123520

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Cap fed, Argentina, 1015
    • Organización medica de Investi
  • Ciudad Autonoma de Buenos Aires, Argentina, 1111
    • Centro de Investigaciones Reumatologicas y Osteologicas
  • San Juan, Argentina, 5400
    • CER San Juan
  • San Miguel, Argentina, T4000AXL
    • Centro Medico Privado de Reumatologia; Reumathology
• Austria
  • Wien, Austria, 1090
    • Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien
• Colombia
  • Barranquilla, Colombia, 00000
    • Centro Integral de Reumatologia del Caribe SAS CIRCARIBE SAS
  • Bogota, Colombia, 110221
    • Centro de Investigacion en Reumatologia y Especialdades Medicas SAS. CIREEM
  • Bogota, Colombia, 110221
    • Riesgo de Fractura S.A.
  • Bogota, Colombia, 111211
    • Fundacion Instituto de Reumatologia Fernando Chalem
  • Bucaramanga, Colombia, 680003
    • Servimed S.A.S.
  • Zipaquirá, Colombia
    • Healthy Medical Center SAS
• Germany
  • Berlin, Germany, 10117
    • Charité Research Organisation GmbH
• Guatemala
  • Guatemala, Guatemala
    • Centro de Estudio y Tratamiento de Enfermedades Reumaticas
  • Guatemala, Guatemala
    • Clinica Privada de Reumatologia Dr. Henry Briones Alvarado
• Italy
  • Abruzzo
    • Torino, Abruzzo, Italy, 10126
      • Azienda Ospedaliera Città della Salute e della Scienza di Torino; Radiology
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Azienda Ospedaliero-Universitaria Policlinico S. Orsola Malpighi; U.O. Malattie Infettive
  • Sicilia
    • Catania, Sicilia, Italy, 95123
      • Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele
  • Toscana
    • Firenze, Toscana, Italy, 50134
      • Azienda Ospedaliero Universitaria Careggi - SOD Reumatologia
• Mexico
  • Guadalajara, Mexico, 44650
    • Javier Orozco Private Practice
  • Mexicali, Mexico, 21200
    • Centro de Investigación; Artritis y Osteoporosis S.C.
  • Mexico, Mexico, 07760
    • Hospital Angeles Lindavista
  • Monterrey, Mexico, 64460
    • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
  • Queretaro, Mexico, 76000
    • Policlinica Medica de Queretaro S.C.
  • BAJA California
    • Tijuana, BAJA California, Mexico, 22010
      • Centro de Investigacion del Noroeste SC
  • Chihuahua
    • Chichuahua, Chihuahua, Mexico, 31000
      • Investigación y Biomedicina de Chihuahua, Sociedad Civil
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • Centro Integral en Reumatología S.A. de C.V. (CIRSA)
  • Yucatan
    • Merida, Yucatan, Mexico
      • Centro Medico de las Américas
    • Mérida, Yucatan, Mexico, 97070
      • Unidad de Atención Medica e Investigacion en Salud (UNAMIS)
• Peru
  • Arequipa, Peru
    • Hogar Clinica San Juan de Dios
  • LIma, Peru, Lima 01
    • Clinica Internacional Sede Lima
  • Lima, Peru, Lima 41
    • Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional
  • Lima, Peru
    • Instituto de Ginecología y Reproducción
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Reumatología
  • Madrid, Spain, 28006
    • Hospital Universitario de la Princesa; Servicio de Reumatologia
  • Malaga, Spain, 29010
    • Hospital Regional Universitario Carlos Haya; Servicio de Psiquiatria
  • Murcia, Spain, 30003
    • Hospital Universitario Reina Sofía; Servicio de Aparato Digestivo
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla; Servicio de Reumatologia
  • LA Coruña
    • A Coruña, LA Coruña, Spain, 15006
      • Complexo Hospitalario Universitario A Coruña; Servicio de Reumatología
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Hospital de Basurto; Servicio de Reumatologia
• United Kingdom
  • Birmingham, United Kingdom, B15 2WB
    • New Queen Elizabeth Hospital Birmingham
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Glasgow, United Kingdom, G4 0SF
    • Glasgow Royal Infirmary
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas NHS Foundation Trust, Guys Hospital
  • London, United Kingdom, E1 4DG
    • Barts Hospital; Department of Rheumatology
  • Newcastle, United Kingdom
    • Newcastle U. Medical School; Institute of Cellular Medicine
  • Oxford, United Kingdom
    • University of Oxford, Botnar Research Centre
  • Plymouth, United Kingdom, Pl6 8DH
    • Derriford Hospital
  • Stevenage, United Kingdom, SG1 4AB
    • Lister Hospital; Rheumatology Dept
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group; Llc, Central
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Arizona Arthritis & Rheumatology Associates, P.C.
    • Mesa, Arizona, United States, 85202
      • Arizona Arthritis and Rheuma
    • Phoenix, Arizona, United States, 85037
      • Arizona Arthritis & Rheumatology Research, PLLC
  • California
    • Covina, California, United States, 91723
      • Medvin Clinical Research
    • La Jolla, California, United States, 92093
      • University of California San Diego
    • Lakewood, California, United States, 90712
      • Advanced Medical Research, LLC
    • Stanford, California, United States, 94304
      • Stanford hospital & Clinics; Investigational Drug Services
  • Florida
    • DeBary, Florida, United States, 32713-1817
      • Omega Research Consultants LLC
    • Hialeah, Florida, United States, 33015-5110
      • San Marcus Research Clinic, Inc.
    • Ormond Beach, Florida, United States, 32174
      • Millenium Research
  • Massachusetts
    • Worcester, Massachusetts, United States, 01610
      • Clinical Pharmacology Study Group
  • Michigan
    • Saint Clair Shores, Michigan, United States, 48080
      • Shores Rheumatology PC
  • New Jersey
    • Freehold, New Jersey, United States
      • Arthritis & Osteoporosis Associates
    • Toms River, New Jersey, United States, 08775
      • Ocean Rheumatology
    • Toms River, New Jersey, United States, 08755
      • Atlantic Coast Rheumatology
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Center for Rheumatology
  • New York
    • Canton, New York, United States, 13617
      • Saint Lawrence Health System; Rheumatology
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • Paramount Medical Research
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
    • Wexford, Pennsylvania, United States, 15090
      • Advanced Rheumatology & Arthritis Research Center
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Low Country Rheumatology, PA
    • Columbia, South Carolina, United States, 29204
      • Columbia Arthritis Center (Partnership Practice)
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute
  • Texas
    • Corpus Christi, Texas, United States, 78404
      • Adriana Pop-Moody MD Clinic PA
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research
    • Houston, Texas, United States, 77089
      • Accurate Clinical Research
    • Houston, Texas, United States, 77058-3675
      • Accurate Clinical Research
    • Houston, Texas, United States, 077099
      • Pioneer Research Solutions
    • Mesquite, Texas, United States, 75150
      • Southwest Rheumatology
    • Stafford, Texas, United States, 77477
      • Accurate Clinical Research, Inc

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of adult-onset RA as defined by the ACR 2010 criteria, for at least 6 months before screening
• Moderately to severely active RA as defined by at least 4/28 tender joints and at least 4/28 swollen joints, and a DAS28 greater than or equal to (≥) 3.2
• For Part 2 only: Active synovitis and/or osteitis as determined by contrast-enhanced magnetic resonance imaging
• Participants must be taking stable dose of anti-TNF-alpha therapies
• Participants on stable oral glucocorticoids within 6 weeks of planned randomization
• Participants taking non-steroidal anti-inflammatory drugs (NSAIDs) intermittently (up to 2-3 times weekly) for short-term relief of pain and participants on regular NSAID use (on stable dose for ≥ 4 weeks)

Exclusion Criteria:

• Parenteral glucocorticoids administration (intramuscular, IV) of ≥50 mg within 6 weeks or less than or equal to (≤) 50 milligrams (mg) within 4 weeks prior to planned randomization, or scheduled parenteral administrations during the study
• Joint(s) injected with intra-articular glucocorticoids or hyaluronic acid within 6 weeks prior to planned randomization
• Active inflammatory diseases of the joints not related to RA
• Systemic autoimmune disease other than RA
• Juvenile idiopathic arthritis or juvenile RA and/or RA developed before the age of 16
• Active fibromyalgia that makes appropriate assessment of RA disease activity challenging in the opinion of the Investigator
• RA participants functional status class IV according to the ACR 1991 criteria
• Participants with severe chronic or recurrent viral, bacterial, parasitic, or fungal infections
• History of active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection
• Any identified confirmed congenital or acquired immunodeficiency
• Abnormal laboratory values and liver function test
• Myocardial infarction within less than 6 months prior to participation in the study
• Severe central or peripheral nervous system diseases

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part 1: Placebo; Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.	Drug: Anti-TNF-alpha; Participants will continue their pre-trial anti-TNF-alpha therapy at a stable dose.; Drug: Methotrexate; Participants will continue their pre-trial methotrexate therapy at a stable dose.; Drug: Placebo; Participants will receive intravenous infusion of placebo.
Experimental: Part 1: RO7123520; Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.	Drug: Anti-TNF-alpha; Participants will continue their pre-trial anti-TNF-alpha therapy at a stable dose.; Drug: Methotrexate; Participants will continue their pre-trial methotrexate therapy at a stable dose.; Drug: RO7123520; Participants will receive intravenous infusion of RO7123520.
Placebo Comparator: Part 2: Placebo; Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.	Drug: Anti-TNF-alpha; Participants will continue their pre-trial anti-TNF-alpha therapy at a stable dose.; Drug: Methotrexate; Participants will continue their pre-trial methotrexate therapy at a stable dose.; Drug: Placebo; Participants will receive intravenous infusion of placebo.
Experimental: Part 2: RO7123520; Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.	Drug: Anti-TNF-alpha; Participants will continue their pre-trial anti-TNF-alpha therapy at a stable dose.; Drug: Methotrexate; Participants will continue their pre-trial methotrexate therapy at a stable dose.; Drug: RO7123520; Participants will receive intravenous infusion of RO7123520.
Placebo Comparator: Part 3: Placebo; Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate. NOTE: Part 3 was not conducted.	Drug: Anti-TNF-alpha; Participants will continue their pre-trial anti-TNF-alpha therapy at a stable dose.; Drug: Methotrexate; Participants will continue their pre-trial methotrexate therapy at a stable dose.; Drug: Placebo; Participants will receive intravenous infusion of placebo.
Experimental: Part 3: RO7123520; Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate. NOTE: Part 3 was not conducted.	Drug: Anti-TNF-alpha; Participants will continue their pre-trial anti-TNF-alpha therapy at a stable dose.; Drug: Methotrexate; Participants will continue their pre-trial methotrexate therapy at a stable dose.; Drug: RO7123520; Participants will receive intravenous infusion of RO7123520.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	Baseline to last participant last visit (approximately 2 years)
Proportion of Participants Achieving an American College of Rheumatology (ACR) 50 Response at Week 12	The ACR50 is a composite measure defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.	Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
Percentage of Participants With Anti-Drug Antibodies		Baseline
Change From Baseline in Bone Mineral Density Lumbar Spine L1-L4 as Assessed by Dual Energy X-ray Absorptiometry (DEXA) Scans		Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12	The CDAI for Rheumatoid Arthritis (RA) assesses the severity of the disease using clinical data. It consists of the Patient Global disease Activity (PGA) estimate and the Evaluator Global disease Activity (EGA) estimate, each of which represent assessments of disease activity on a scale of 1-10, with 10 being maximum activity.	Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
Change From Baseline in Disease Activity Score 28 (DAS28) at Week 12	The DAS28 is a combined index for measuring disease activity in RA; the "28" refers to the number of joints included in the assessment. The index includes swollen and tender joint counts, acute phase response, and general arthritis disease activity status. An overall disease activity score of 5.1 or greater implies active disease, less than 3.2 implies low disease activity, and less that 2.6 implies disease remission.	Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
Percentage of Participants Achieving DAS28 Remission at Week 12	The DAS28 is a combined index for measuring disease activity in RA; the "28" refers to the number of joints included in the assessment. The index includes swollen and tender joint counts, acute phase response, and general arthritis disease activity status. An overall disease activity score of 5.1 or greater implies active disease, less than 3.2 implies low disease activity, and less that 2.6 implies disease remission.	Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
Percentage of Participants Achieving CDAI Remission at Week 12	The CDAI for Rheumatoid Arthritis (RA) assesses the severity of the disease using clinical data. It consists of the Patient Global disease Activity (PGA) estimate and the Evaluator Global disease Activity (EGA) estimate, each of which represent assessments of disease activity on a scale of 1-10, with 10 being maximum activity. CDAI remission is defined as a score of less than or equal to 2.8.	Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
Percentage of Participants Achieving ACR20 Response at Week 12	The ACR20 is a composite measure defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.	Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
Percentage of Participants Achieving ACR70 Response at Week 12	The ACR70 is a composite measure defined as both improvement of 70% in the number of tender and number of swollen joints, and a 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.	Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
Change From Baseline in Simple Disease Activity Index (SDAI) Score at Week 12	The SDAI consists of 5 parameters used to assess RA disease activity: 28-joint count assessments of tenderness and swelling, participant and investigator global assessments, and CRP levels. A composite score is produced, with remission defined as an SDAI of <3.3, low disease activity as ≤11, moderate disease activity as ≤26 and high disease activity as >26.	Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
Change From Baseline in the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12	The HAQ-DI is a 20-item, validated questionnaire used to assess difficulty in performing activities of daily living. The questionnaire assesses eight domains of physical functioning: Dressing and Grooming (2 items), Hygiene (3 items), Arising (2 items), Reach (2 items), Eating (3 items), Grip (3 items), Walking (2 items), Common Daily Activities (3 items). The questions assess usual abilities ranging from 0 "without any difficulty" to 3 "unable to do." A lower HAQ-DI score indicates better quality of life. Subscale scores are combined and the mean value is reported for each arm per timepoint.	Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
Serum RO7123520 Concentration		Pre-dose (0 hour), 1 hour post infusion (duration of infusion: approximately 1 hour) on Days 1, 14, 28, 56; Pre-dose (0 hour) on Days 84, 112
Synovial Fluid RO7123520 Concentration		Pre-dose (0 hour) on Days 1, 84

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2016
• Primary Completion (Actual): November 6, 2018
• Study Completion (Actual): November 6, 2018

Study Registration Dates

• First Submitted: December 20, 2016
• First Submitted That Met QC Criteria: December 20, 2016
• First Posted (Estimate): December 22, 2016

Study Record Updates

• Last Update Posted (Actual): January 29, 2020
• Last Update Submitted That Met QC Criteria: January 17, 2020
• Last Verified: January 1, 2020

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; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: BP39261; 2016-002126-36 (EudraCT Number)