Clinical trial NCT03001219: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-12-22
Enrollment: 109
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline to last participant last visit (approximately 2 years)
measure: Proportion of Participants Achieving an American College of Rheumatology (ACR) 50 Response at Week 12
timeFrame: Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
measure: Percentage of Participants With Anti-Drug Antibodies
timeFrame: Baseline
measure: Change From Baseline in Bone Mineral Density Lumbar Spine L1-L4 as Assessed by Dual Energy X-ray Absorptiometry (DEXA) Scans
timeFrame: Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
Secondary outcomes:
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12
timeFrame: Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
measure: Change From Baseline in Disease Activity Score 28 (DAS28) at Week 12
timeFrame: Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
measure: Percentage of Participants Achieving DAS28 Remission at Week 12
timeFrame: Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
measure: Percentage of Participants Achieving CDAI Remission at Week 12
timeFrame: Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
measure: Percentage of Participants Achieving ACR20 Response at Week 12
timeFrame: Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
measure: Percentage of Participants Achieving ACR70 Response at Week 12
timeFrame: Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
measure: Change From Baseline in Simple Disease Activity Index (SDAI) Score at Week 12
timeFrame: Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
measure: Change From Baseline in the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12
timeFrame: Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
measure: Serum RO7123520 Concentration
timeFrame: 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
measure: Synovial Fluid RO7123520 Concentration
timeFrame: Pre-dose (0 hour) on Days 1, 84
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group; Llc, Central
state: Alabama
city: Glendale
country: United States
facility: Arizona Arthritis & Rheumatology Associates, P.C.
state: Arizona
city: Mesa
country: United States
facility: Arizona Arthritis and Rheuma
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arthritis & Rheumatology Research, PLLC
state: Arizona
city: Covina
country: United States
facility: Medvin Clinical Research
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Lakewood
country: United States
facility: Advanced Medical Research, LLC
state: California
city: Stanford
country: United States
facility: Stanford hospital & Clinics; Investigational Drug Services
state: California
city: DeBary
country: United States
facility: Omega Research Consultants LLC
state: Florida
city: Hialeah
country: United States
facility: San Marcus Research Clinic, Inc.
state: Florida
city: Ormond Beach
country: United States
facility: Millenium Research
state: Florida
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Saint Clair Shores
country: United States
facility: Shores Rheumatology PC
state: Michigan
city: Freehold
country: United States
facility: Arthritis & Osteoporosis Associates
state: New Jersey
city: Toms River
country: United States
facility: Atlantic Coast Rheumatology
state: New Jersey
city: Toms River
country: United States
facility: Ocean Rheumatology
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Center For Rheumatology
state: New Mexico
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials
state: New Mexico
city: Canton
country: United States
facility: Saint Lawrence Health System; Rheumatology
state: New York
city: Middleburg Heights
country: United States
facility: Paramount Medical Research
state: Ohio
city: Duncansville
country: United States
facility: Altoona Center For Clinical Research
state: Pennsylvania
city: Wexford
country: United States
facility: Advanced Rheumatology & Arthritis Research Center
state: Pennsylvania
city: Charleston
country: United States
facility: Low Country Rheumatology, PA
state: South Carolina
city: Columbia
country: United States
facility: Columbia Arthritis Center (Partnership Practice)
state: South Carolina
city: Jackson
country: United States
facility: West Tennessee Research Institute
state: Tennessee
city: Corpus Christi
country: United States
facility: Adriana Pop-Moody MD Clinic PA
state: Texas
city: Dallas
country: United States
facility: Metroplex Clinical Research
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research
state: Texas
city: Mesquite
country: United States
facility: Southwest Rheumatology
state: Texas
city: Stafford
country: United States
facility: Accurate Clinical Research, Inc
state: Texas
city: Cap fed
country: Argentina
facility: Organización medica de Investi
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Centro de Investigaciones Reumatologicas y Osteologicas
city: San Juan
country: Argentina
facility: Cer San Juan
city: San Miguel
country: Argentina
facility: Centro Medico Privado de Reumatologia; Reumathology
city: Wien
country: Austria
facility: Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien
city: Barranquilla
country: Colombia
facility: Centro Integral de Reumatologia del Caribe SAS CIRCARIBE SAS
city: Bogota
country: Colombia
facility: Centro de Investigacion en Reumatologia y Especialdades Medicas SAS. CIREEM
city: Bogota
country: Colombia
facility: Riesgo de Fractura S.A.
city: Bogota
country: Colombia
facility: Fundación Instituto de Reumatología Fernando Chalem
city: Bucaramanga
country: Colombia
facility: Servimed S.A.S.
city: Zipaquirá
country: Colombia
facility: Healthy Medical Center SAS
city: Berlin
country: Germany
facility: Charité Research Organisation GmbH
city: Guatemala
country: Guatemala
facility: Centro de Estudio y Tratamiento de Enfermedades Reumaticas
city: Guatemala
country: Guatemala
facility: Clinica Privada de Reumatologia Dr. Henry Briones Alvarado
city: Torino
country: Italy
facility: Azienda Ospedaliera Città della Salute e della Scienza di Torino; Radiology
state: Abruzzo
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico S. Orsola Malpighi; U.O. Malattie Infettive
state: Emilia-Romagna
city: Catania
country: Italy
facility: Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele
state: Sicilia
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi - SOD Reumatologia
state: Toscana
city: Tijuana
country: Mexico
facility: Centro de Investigacion del Noroeste SC
state: BAJA California
city: Chichuahua
country: Mexico
facility: Investigacion y Biomedicina de Chihuahua, Sociedad Civil
state: Chihuahua
city: Guadalajara
country: Mexico
facility: Centro Integral en Reumatología S.A. de C.V. (CIRSA)
state: Jalisco
city: Merida
country: Mexico
facility: Centro Médico de las Américas
state: Yucatan
city: Mérida
country: Mexico
facility: Unidad de Atencion Medica e Investigacion en Salud (UNAMIS)
state: Yucatan
city: Guadalajara
country: Mexico
facility: Javier Orozco Private Practice
city: Mexicali
country: Mexico
facility: Centro de Investigación; Artritis y Osteoporosis S.C.
city: Mexico
country: Mexico
facility: Hospital Angeles Lindavista
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
city: Queretaro
country: Mexico
facility: Policlinica Medica de Queretaro S.C.
city: Arequipa
country: Peru
facility: Hogar Clínica San Juan de Dios
city: LIma
country: Peru
facility: Clinica Internacional Sede Lima
city: Lima
country: Peru
facility: Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional
city: Lima
country: Peru
facility: Instituto de Ginecología y Reproducción
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla; Servicio de Reumatologia
state: Cantabria
city: A Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña; Servicio de Reumatología
state: LA Coruña
city: Bilbao
country: Spain
facility: Hospital de Basurto; Servicio de Reumatologia
state: Vizcaya
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa; Servicio de Reumatologia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon; Servicio de Reumatología
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya; Servicio de Psiquiatria
city: Murcia
country: Spain
facility: Hospital Universitario Reina Sofía; Servicio de Aparato Digestivo
city: Birmingham
country: United Kingdom
facility: New Queen Elizabeth Hospital Birmingham
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: London
country: United Kingdom
facility: Barts Hospital; Department of Rheumatology
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust, Guys Hospital
city: Newcastle
country: United Kingdom
facility: Newcastle U. Medical School; Institute of Cellular Medicine
city: Oxford
country: United Kingdom
facility: University of Oxford, Botnar Research Centre
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Stevenage
country: United Kingdom
facility: Lister Hospital; Rheumatology Dept
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: