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

NCT03001219 | Terminated Phase 2 Results

• 2 other identifiers: BP392612016-002126-36
• Study Type: interventional
• Target: 109
• Locations: 11 countries
• Sites: 81

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (10)

• Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12

  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

  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

  Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

• Percentage of Participants Achieving CDAI Remission at Week 12

  Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

• Percentage of Participants Achieving ACR20 Response at Week 12

  Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

Study Arms (6)

Part 1: Placebo

PLACEBO COMPARATOR

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; Drug: Methotrexate; Drug: Placebo

Part 1: RO7123520

EXPERIMENTAL

Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.

Drug: Anti-TNF-alpha; Drug: Methotrexate; Drug: RO7123520

Part 2: Placebo

PLACEBO COMPARATOR

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; Drug: Methotrexate; Drug: Placebo

Part 2: RO7123520

EXPERIMENTAL

Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.

Drug: Anti-TNF-alpha; Drug: Methotrexate; Drug: RO7123520

Part 3: Placebo

PLACEBO COMPARATOR

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; Drug: Methotrexate; Drug: Placebo

Part 3: RO7123520

EXPERIMENTAL

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; Drug: Methotrexate; Drug: RO7123520

Interventions

Anti-TNF-alpha DRUG

Participants will continue their pre-trial anti-TNF-alpha therapy at a stable dose.

Part 1: Placebo; Part 1: RO7123520; Part 2: Placebo; Part 2: RO7123520; Part 3: Placebo; Part 3: RO7123520

Methotrexate DRUG

Participants will continue their pre-trial methotrexate therapy at a stable dose.

Part 1: Placebo; Part 1: RO7123520; Part 2: Placebo; Part 2: RO7123520; Part 3: Placebo; Part 3: RO7123520

Placebo DRUG

Participants will receive intravenous infusion of placebo.

Part 1: Placebo; Part 2: Placebo; Part 3: Placebo

RO7123520 DRUG

Participants will receive intravenous infusion of RO7123520.

Part 1: RO7123520; Part 2: RO7123520; Part 3: RO7123520

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (81)

Pinnacle Research Group; Llc, Central

Anniston, Alabama, 36207, United States

Location

Arizona Arthritis & Rheumatology Associates, P.C.

Glendale, Arizona, 85306, United States

Location

Arizona Arthritis and Rheuma

Mesa, Arizona, 85202, United States

Location

Arizona Arthritis & Rheumatology Research, PLLC

Phoenix, Arizona, 85037, United States

Location

Medvin Clinical Research

Covina, California, 91723, United States

Location

University of California San Diego

La Jolla, California, 92093, United States

Location

Advanced Medical Research, LLC

Lakewood, California, 90712, United States

Location

Stanford hospital & Clinics; Investigational Drug Services

Stanford, California, 94304, United States

Location

Omega Research Consultants LLC

DeBary, Florida, 32713-1817, United States

Location

San Marcus Research Clinic, Inc.

Hialeah, Florida, 33015-5110, United States

Location

Millenium Research

Ormond Beach, Florida, 32174, United States

Location

Clinical Pharmacology Study Group

Worcester, Massachusetts, 01610, United States

Location

Shores Rheumatology PC

Saint Clair Shores, Michigan, 48080, United States

Location

Arthritis & Osteoporosis Associates

Freehold, New Jersey, United States

Location

Atlantic Coast Rheumatology

Toms River, New Jersey, 08755, United States

Location

Ocean Rheumatology

Toms River, New Jersey, 08775, United States

Location

Albuquerque Center For Rheumatology

Albuquerque, New Mexico, 87102, United States

Location

Albuquerque Clinical Trials

Albuquerque, New Mexico, 87102, United States

Location

Saint Lawrence Health System; Rheumatology

Canton, New York, 13617, United States

Location

Paramount Medical Research

Middleburg Heights, Ohio, 44130, United States

Location

Altoona Center For Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Advanced Rheumatology & Arthritis Research Center

Wexford, Pennsylvania, 15090, United States

Location

Low Country Rheumatology, PA

Charleston, South Carolina, 29406, United States

Location

Columbia Arthritis Center (Partnership Practice)

Columbia, South Carolina, 29204, United States

Location

West Tennessee Research Institute

Jackson, Tennessee, 38305, United States

Location

Adriana Pop-Moody MD Clinic PA

Corpus Christi, Texas, 78404, United States

Location

Metroplex Clinical Research

Dallas, Texas, 75231, United States

Location

Pioneer Research Solutions

Houston, Texas, 077099, United States

Location

Accurate Clinical Research

Houston, Texas, 77058-3675, United States

Location

Accurate Clinical Research

Houston, Texas, 77089, United States

Location

Southwest Rheumatology

Mesquite, Texas, 75150, United States

Location

Accurate Clinical Research, Inc

Stafford, Texas, 77477, United States

Location

Centro de Investigaciones Reumatologicas y Osteologicas

Buenos Aires, 1111, Argentina

Location

Organización medica de Investi

Cap Fed, 1015, Argentina

Location

Cer San Juan

San Juan, 5400, Argentina

Location

Centro Medico Privado de Reumatologia; Reumathology

San Miguel, T4000AXL, Argentina

Location

Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien

Vienna, 1090, Austria

Location

Centro Integral de Reumatologia del Caribe SAS CIRCARIBE SAS

Barranquilla, 00000, Colombia

Location

Centro de Investigacion en Reumatologia y Especialdades Medicas SAS. CIREEM

Bogotá, 110221, Colombia

Location

Riesgo de Fractura S.A.

Bogotá, 110221, Colombia

Location

Fundación Instituto de Reumatología Fernando Chalem

Bogotá, 111211, Colombia

Location

Servimed S.A.S.

Bucaramanga, 680003, Colombia

Location

Healthy Medical Center SAS

Zipaquirá, Colombia

Location

Charité Research Organisation GmbH

Berlin, 10117, Germany

Location

Centro de Estudio y Tratamiento de Enfermedades Reumaticas

Guatemala City, Guatemala

Location

Clinica Privada de Reumatologia Dr. Henry Briones Alvarado

Guatemala City, Guatemala

Location

Azienda Ospedaliera Città della Salute e della Scienza di Torino; Radiology

Torino, Abruzzo, 10126, Italy

Location

Azienda Ospedaliero-Universitaria Policlinico S. Orsola Malpighi; U.O. Malattie Infettive

Bologna, Emilia-Romagna, 40138, Italy

Location

Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele

Catania, Sicily, 95123, Italy

Location

Azienda Ospedaliero Universitaria Careggi - SOD Reumatologia

Florence, Tuscany, 50134, Italy

Location

Investigacion y Biomedicina de Chihuahua, Sociedad Civil

Chichuahua, Chihuahua, 31000, Mexico

Location

Centro de Investigacion del Noroeste SC

Tijuana, Estado de Baja California, 22010, Mexico

Location

Centro Integral en Reumatología S.A. de C.V. (CIRSA)

Guadalajara, Jalisco, 44160, Mexico

Location

Unidad de Atencion Medica e Investigacion en Salud (UNAMIS)

Mérida, Yucatán, 97070, Mexico

Location

Centro Médico de las Américas

Mérida, Yucatán, Mexico

Location

Javier Orozco Private Practice

Guadalajara, 44650, Mexico

Location

Centro de Investigación; Artritis y Osteoporosis S.C.

Mexicali, 21200, Mexico

Location

Hospital Angeles Lindavista

México, 07760, Mexico

Location

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

Monterrey, 64460, Mexico

Location

Policlinica Medica de Queretaro S.C.

Querétaro, 76000, Mexico

Location

Hogar Clínica San Juan de Dios

Arequipa, Peru

Location

Clinica Internacional Sede Lima

Lima, Lima 01, Peru

Location

Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional

Lima, Lima 41, Peru

Location

Instituto de Ginecología y Reproducción

Lima, Peru

Location

Hospital Universitario Marques de Valdecilla; Servicio de Reumatologia

Santander, Cantabria, 39008, Spain

Location

Complexo Hospitalario Universitario A Coruña; Servicio de Reumatología

A Coruña, LA Coruña, 15006, Spain

Location

Hospital de Basurto; Servicio de Reumatologia

Bilbao, Vizcaya, 48013, Spain

Location

Hospital Universitario de la Princesa; Servicio de Reumatologia

Madrid, 28006, Spain

Location

Hospital General Universitario Gregorio Marañon; Servicio de Reumatología

Madrid, 28007, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Regional Universitario Carlos Haya; Servicio de Psiquiatria

Málaga, 29010, Spain

Location

Hospital Universitario Reina Sofía; Servicio de Aparato Digestivo

Murcia, 30003, Spain

Location

New Queen Elizabeth Hospital Birmingham

Birmingham, B15 2WB, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, G4 0SF, United Kingdom

Location

Barts Hospital; Department of Rheumatology

London, E1 4DG, United Kingdom

Location

Guys and St Thomas NHS Foundation Trust, Guys Hospital

London, SE1 9RT, United Kingdom

Location

Newcastle U. Medical School; Institute of Cellular Medicine

Newcastle, United Kingdom

Location

University of Oxford, Botnar Research Centre

Oxford, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Lister Hospital; Rheumatology Dept

Stevenage, SG1 4AB, United Kingdom

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The trial was prematurely terminated due to a lack of efficacy of the investigational drug. There were no serious safety issues or adverse events contributing to the decision to terminate early.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2016
• First Posted: December 22, 2016
• Study Start: December 22, 2016
• Primary Completion: November 6, 2018
• Study Completion: November 6, 2018
• Last Updated: January 29, 2020
• Results First Posted: January 29, 2020

Record last verified: 2020-01

Locations

GU (2); GB (9); IT (4); AR (4); DE (1); CO (6); US (32); ME (10); AU (1); PE (4); ES (8)