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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03001219
• Other study ID #: BP39261
• Secondary ID: 2016-002126-36
• Status: Terminated
• Phase: Phase 2
• Start date: December 22, 2016
• Est. completion date: November 6, 2018

Study information

• Verified date: January 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 109
• Est. completion date: November 6, 2018
• Est. primary completion date: November 6, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Anti-TNF-alpha
Participants will continue their pre-trial anti-TNF-alpha therapy at a stable dose.
• Methotrexate
Participants will continue their pre-trial methotrexate therapy at a stable dose.
• Placebo
Participants will receive intravenous infusion of placebo.
• RO7123520
Participants will receive intravenous infusion of RO7123520.

Locations

Country	Name	City	State
Argentina	Organización medica de Investi	Cap fed
Argentina	Centro de Investigaciones Reumatologicas y Osteologicas	Ciudad Autonoma de Buenos Aires
Argentina	Cer San Juan	San Juan
Argentina	Centro Medico Privado de Reumatologia; Reumathology	San Miguel
Austria	Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien	Wien
Colombia	Centro Integral de Reumatologia del Caribe SAS CIRCARIBE SAS	Barranquilla
Colombia	Centro de Investigacion en Reumatologia y Especialdades Medicas SAS. CIREEM	Bogota
Colombia	Fundación Instituto de Reumatología Fernando Chalem	Bogota
Colombia	Riesgo de Fractura S.A.	Bogota
Colombia	Servimed S.A.S.	Bucaramanga
Colombia	Healthy Medical Center SAS	Zipaquirá
Germany	Charité Research Organisation GmbH	Berlin
Guatemala	Centro de Estudio y Tratamiento de Enfermedades Reumaticas	Guatemala
Guatemala	Clinica Privada de Reumatologia Dr. Henry Briones Alvarado	Guatemala
Italy	Azienda Ospedaliero-Universitaria Policlinico S. Orsola Malpighi; U.O. Malattie Infettive	Bologna	Emilia-Romagna
Italy	Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele	Catania	Sicilia
Italy	Azienda Ospedaliero Universitaria Careggi - SOD Reumatologia	Firenze	Toscana
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino; Radiology	Torino	Abruzzo
Mexico	Investigacion y Biomedicina de Chihuahua, Sociedad Civil	Chichuahua	Chihuahua
Mexico	Centro Integral en Reumatología S.A. de C.V. (CIRSA)	Guadalajara	Jalisco
Mexico	Javier Orozco Private Practice	Guadalajara
Mexico	Centro Médico de las Américas	Merida	Yucatan
Mexico	Unidad de Atencion Medica e Investigacion en Salud (UNAMIS)	Mérida	Yucatan
Mexico	Centro de Investigación; Artritis y Osteoporosis S.C.	Mexicali
Mexico	Hospital Angeles Lindavista	Mexico
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey
Mexico	Policlinica Medica de Queretaro S.C.	Queretaro
Mexico	Centro de Investigacion del Noroeste SC	Tijuana	BAJA California
Peru	Hogar Clínica San Juan de Dios	Arequipa
Peru	Clinica Internacional Sede Lima	LIma
Peru	Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional	Lima
Peru	Instituto de Ginecología y Reproducción	Lima
Spain	Complexo Hospitalario Universitario A Coruña; Servicio de Reumatología	A Coruña	LA Coruña
Spain	Hospital de Basurto; Servicio de Reumatologia	Bilbao	Vizcaya
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Reumatología	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de la Princesa; Servicio de Reumatologia	Madrid
Spain	Hospital Regional Universitario Carlos Haya; Servicio de Psiquiatria	Malaga
Spain	Hospital Universitario Reina Sofía; Servicio de Aparato Digestivo	Murcia
Spain	Hospital Universitario Marques de Valdecilla; Servicio de Reumatologia	Santander	Cantabria
United Kingdom	New Queen Elizabeth Hospital Birmingham	Birmingham
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	Glasgow Royal Infirmary	Glasgow
United Kingdom	Barts Hospital; Department of Rheumatology	London
United Kingdom	Guys and St Thomas NHS Foundation Trust, Guys Hospital	London
United Kingdom	Newcastle U. Medical School; Institute of Cellular Medicine	Newcastle
United Kingdom	University of Oxford, Botnar Research Centre	Oxford
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Lister Hospital; Rheumatology Dept	Stevenage
United States	Albuquerque Center For Rheumatology	Albuquerque	New Mexico
United States	Albuquerque Clinical Trials	Albuquerque	New Mexico
United States	Pinnacle Research Group; Llc, Central	Anniston	Alabama
United States	Saint Lawrence Health System; Rheumatology	Canton	New York
United States	Low Country Rheumatology, PA	Charleston	South Carolina
United States	Columbia Arthritis Center (Partnership Practice)	Columbia	South Carolina
United States	Adriana Pop-Moody MD Clinic PA	Corpus Christi	Texas
United States	Medvin Clinical Research	Covina	California
United States	Metroplex Clinical Research	Dallas	Texas
United States	Omega Research Consultants LLC	DeBary	Florida
United States	Altoona Center For Clinical Research	Duncansville	Pennsylvania
United States	Arthritis & Osteoporosis Associates	Freehold	New Jersey
United States	Arizona Arthritis & Rheumatology Associates, P.C.	Glendale	Arizona
United States	San Marcus Research Clinic, Inc.	Hialeah	Florida
United States	Accurate Clinical Research	Houston	Texas
United States	Accurate Clinical Research	Houston	Texas
United States	Pioneer Research Solutions	Houston	Texas
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	University of California San Diego	La Jolla	California
United States	Advanced Medical Research, LLC	Lakewood	California
United States	Arizona Arthritis and Rheuma	Mesa	Arizona
United States	Southwest Rheumatology	Mesquite	Texas
United States	Paramount Medical Research	Middleburg Heights	Ohio
United States	Millenium Research	Ormond Beach	Florida
United States	Arizona Arthritis & Rheumatology Research, PLLC	Phoenix	Arizona
United States	Shores Rheumatology PC	Saint Clair Shores	Michigan
United States	Accurate Clinical Research, Inc	Stafford	Texas
United States	Stanford hospital & Clinics; Investigational Drug Services	Stanford	California
United States	Atlantic Coast Rheumatology	Toms River	New Jersey
United States	Ocean Rheumatology	Toms River	New Jersey
United States	Advanced Rheumatology & Arthritis Research Center	Wexford	Pennsylvania
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Colombia,  Germany,  Guatemala,  Italy,  Mexico,  Peru,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	Percentage of Participants With Anti-Drug Antibodies		Baseline
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	Synovial Fluid RO7123520 Concentration		Pre-dose (0 hour) on Days 1, 84