A Study to Assess the Efficacy and Safety of RO7790121 in Participants With Moderate to Severe Rheumatoid Arthritis Who Have Not Responded to or Who Cannot Tolerate Tumor Necrosis Factor (TNF) and/or Janus Kinase (JAK Inhibitors)

A Phase II, Multicenter, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of RO7790121 in Participants With Moderate to Severe Rheumatoid Arthritis Who Have an Inadequate Response or Intolerance to TNF and/or JAK Inhibitors

This study will assess the efficacy and safety of Afimkibart (also known as RO7790121) compared with placebo in participants with moderate to severe rheumatoid arthritis (RA) who have an inadequate response or intolerance to TNF and/or JAK inhibitors.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Placebo; Drug: Afimkibart

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: WA45846 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global.rochegenentechtrials@roche.com
• Study Contact Backup: Name: Fastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina, C1417EYH
    • Recruiting
    • Centro Privado de Medicina Familiar - Mind Out Research
  • Buenos Aires
    • Ciudad Autnoma de Buenos Aires, Buenos Aires, Argentina, C1427
      • Recruiting
      • Centro Médico Arsema
    • Mar del Plata, Buenos Aires, Argentina, 7600
      • Recruiting
      • Centro de Investigaciones Médicas Mar del Plata
  • Ciudad Autonoma Buenos Aires
    • Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina, C1406AGA
      • Recruiting
      • APRILLUS Asistencia e Investigacion
• Belgium
  • Brussels, Belgium, 1070
    • Recruiting
    • HUB Erasme
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
• Brazil
  • Federal District
    • Brasília, Federal District, Brazil, 70200-730
      • Recruiting
      • L2IP ?Instituto de Pesquisas Clínicas Ltda.
  • Mato Grosso
    • Cuiab, Mato Grosso, Brazil, 78020-500
      • Recruiting
      • IPC MT Instituto de Pesquisas Clinicas do Mato Grosso
  • Minas Gerais
    • Juiz de Fora, Minas Gerais, Brazil, 36010-570
      • Recruiting
      • Centro Mineiro de Pesquisa - CMiP
  • Paraná
    • Curitiba, Paraná, Brazil, 80030-110
      • Recruiting
      • Centro de Estudos em Terapias Inovadoras ? CETI
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Recruiting
      • Hospital So Lucas da PUCRS
  • São Paulo
    • Ribeirão Preto, São Paulo, Brazil, 14048-900
      • Recruiting
      • Hospital das Clínicas FMRP-USP
    • So Paulo, São Paulo, Brazil, 04266-010
      • Recruiting
      • CEPIC - Centro Paulista de Investigao Clnica e Servios Mdicos
• Denmark
  • Frederiksberg, Denmark, 2000
    • Recruiting
    • Bispebjerg og Frederiksberg Hospital
  • Kge, Denmark, 4600
    • Recruiting
    • Sjllands Universitetshospital
• France
  • Paris, France, 75014
    • Recruiting
    • Hpital Cochin
  • Bas Rhin
    • Strasbourg, Bas Rhin, France, 67091
      • Recruiting
      • CHU Strasbourg Hpital Hautepierre
  • Bouches-du-Rhne
    • Marseille, Bouches-du-Rhne, France, 13005
      • Recruiting
      • Hôpital de la Conception
  • Herault
    • Montpellier, Herault, France, 34295
      • Recruiting
      • Hopital Lapeyronie
  • Lot Et Garonne
    • Toulouse, Lot Et Garonne, France, 31059
      • Recruiting
      • Hopital Purpan
• Germany
  • North Rhine-Westphalia
    • Herne, North Rhine-Westphalia, Germany, 44649
      • Recruiting
      • Rheumazentrum Ruhrgebiet
  • Saxony
    • Dresden, Saxony, Germany, 01067
      • Recruiting
      • Städtisches Klinik Dresden-Friedrichstadt
• Italy
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Lombardy
    • Rozzano, Lombardy, Italy, 20089
      • Recruiting
      • Istituto Clinico Humanitas
• Poland
  • Bytom, Poland, 41-902
    • Recruiting
    • Nzoz Bif-Med
  • Elbl?g, Poland, 82-300
    • Recruiting
    • Centrum Kliniczno-Badawcze J. Brzezicki, B. Górnikiewicz-Brzezicka Lekarze Spó?ka Partne
  • Krakow, Poland, 30-002
    • Recruiting
    • Malopolskie Badania Kliniczne
  • Lublin, Poland, 20-607
    • Recruiting
    • Zespol Poradni Specjalistycznych REUMED
  • Nowa Sól, Poland, 67-100
    • Recruiting
    • Twoja Przychodnia NCM
  • Warsaw, Poland, 02-665
    • Recruiting
    • Centrum Medyczne Reuma Park
  • Warsaw, Poland, 02-637
    • Recruiting
    • Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Eleonory Reicher
  • Wroclaw, Poland, 52-210
    • Recruiting
    • Reumatop Spolka Jawna
• Spain
  • Málaga, Spain, 29009
    • Recruiting
    • Hospital Regional Universitario de Málaga
  • Seville, Spain, 41009
    • Recruiting
    • Hospital Universitario Virgen Macarena
  • Seville, Spain, 41010
    • Recruiting
    • Hospital Quironsalud Infanta Luisa
• United Kingdom
  • Barnet, United Kingdom, EN5 3DJ
    • Recruiting
    • Barnet Hospital
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE1 5WW
      • Recruiting
      • Leicester Royal Infirmary
  • South Yorkshire
    • Doncaster, South Yorkshire, United Kingdom, DN2 5LT
      • Recruiting
      • Doncaster Royal Infirmary
  • Tyne & Wear
    • Newcastle upon Tyne, Tyne & Wear, United Kingdom, NE29 8NH
      • Recruiting
      • North Tyneside General Hospital
• United States
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Recruiting
      • SunValley Arthritis Center Ltd.
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars Sinai Medical Center
    • Upland, California, United States, 91786
      • Recruiting
      • Inland Rheumatology Clinical Trials Incorporated
  • Florida
    • Tamarac, Florida, United States, 33321
      • Recruiting
      • West Broward Rheumatology Associates, Inc.
  • Illinois
    • Willowbrook, Illinois, United States, 60527
      • Recruiting
      • Willow Rheumatology and Wellness PLLC
  • Louisiana
    • Lake Charles, Louisiana, United States, 70605
      • Recruiting
      • Accurate Clinical Research Inc.
  • Ohio
    • Columbus, Ohio, United States, 43203
      • Recruiting
      • Ohio State University Wexner Medical Center
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Recruiting
      • Altoona Center for Clinical Research
  • Texas
    • Houston, Texas, United States, 77089
      • Recruiting
      • Accurate Clinical Management
    • Tomball, Texas, United States, 77375
      • Recruiting
      • DM Clinical Research
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Recruiting
      • Tidewater Clinical Research
  • Wisconsin
    • Glendale, Wisconsin, United States, 53217
      • Recruiting
      • Rheumatic Disease Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has moderate to severe active RA defined by the presence of >=6 swollen joints and >=6 tender joints at screening and baseline (based on 66/68-joint count)
• Diagnosis of RA for >=3 months and also fulfills the 2010 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria for RA
• Demonstrated an inadequate response or loss of response to or intolerance to >=1 conventional synthetic disease-modifying antirheumatic drug (csDMARD)

Exclusion Criteria:

• Have failed more than two TNF inhibitors or JAK inhibitors
• Class IV RA according to ACR revised response criteria (Hochberg et al. 1992)
• Past or current use of other biologic disease-modifying antirheumatic drugs (bDMARDs) (excluding TNF inhibitors) or rituximab
• Treatment with investigational therapy within 4 weeks or within 5 half-lives of the investigational therapy, whichever is longer, prior to initiation of study treatment.
• History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than RA
• Has been treated with intra-articular, intramuscular, intravenous, trigger point or tender point, intra-bursa, or intra-tendon sheath corticosteroids in the preceding 8 weeks prior to the first dose of study drug
• History of a severe allergic reaction or anaphylactic reaction or known hypersensitivity to any component of the study drug (or its excipients) and/or other products in the same class
• Any major surgery within 6 weeks prior to screening or a major surgery planned during the study
• Any serious, chronic and/or unstable pre-existing medical, psychiatric, or other- condition
• History of malignancy, with the exception non-metastatic basal cell or cutaneous squamous cell cancer adequately treated with electrodesiccation and curettage or resection or in situ cervical cancer adequately treated and cured
• 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
• History of organ transplant
• Any identified confirmed congenital or acquired immunodeficiency
• Abnormal laboratory values and liver function test

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Afimkibart Group I; Participants will receive afimkibart via subcutaneous (SC) injection.	Drug: Afimkibart; Afimkibart will be administered as SC injection.; Other Names: RVT-3101; RO7790121; PF 06480605
Experimental: Afimkibart Group II; Participants will receive afimkibart via SC injection.	Drug: Afimkibart; Afimkibart will be administered as SC injection.; Other Names: RVT-3101; RO7790121; PF 06480605
Placebo Comparator: Placebo; Participants will receive afimkibart matched placebo via SC injection.	Drug: Placebo; Placebo will be administered as SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Disease Activity Score-28 for Rheumatoid Arthritis with C-Reactive Protein (DAS28-CRP)	Baseline, At Week 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)	At Week 14
Change from Baseline Disease Activity Score-28 for Rheumatoid Arthritis with Erythrocyte Sedimentation Rate (DAS28-ESR) Score	Baseline, At Week 14 and Week 24
Change From Baseline in the ACR Core Set - Swollen Joint Count (SJC)	Baseline, At Week 14 and Week 24
Change From Baseline in the ACR Core Set - Tender Joint Count (TJC)	Baseline, At Week 14 and Week 24
Change From Baseline in the ACR Core Set - Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS)	Baseline, At Week 14 and Week 24
Change From Baseline in the ACR Core Set - Patient's Global Assessment of Arthritis Pain-Visual Analog Scale (PGA Arthritis Pain-VAS)	Baseline, At Week 14 and Week 24
Change From Baseline in the ACR Core Set - Patient's Global Assessment of Disease Activity-Visual Analog Scale (PaGADA-VAS)	Baseline, At Week 14 and Week 24
Change From Baseline in the ACR Core Set - Health Assessment Questionnaire- Disability Index (HAQ-DI)	Baseline, At Week 14 and Week 24
Change From Baseline in the ACR Core Set - High-sensitivity C-reactive Protein (hsCRP)	Baseline, At Week 14 and Week 24
Change from Baseline in ACR20, ACR50 and ACR70 Response Rate	Baseline, At Week 24
Change from Baseline in Simplified Disease Activity Index (SDAI) Score	Baseline, At Week 14 and Week 24
Change from Baseline in Clinical Disease Activity Index (CDAI) Score	Baseline, At Week 14 and Week 24
Change from Baseline in Short Form-36 Health Survey (SF-36) Score	Baseline, At Week 14 and Week 24
Change from Baseline Disease Activity Score-28 for Rheumatoid Arthritis with C-Reactive Protein (DAS28-CRP) Score	Baseline, At Week 24
Percentage of Participants With Adverse Events (AEs)	Up to Week 38
Serum Concentration of RO7790121 at Specified Timepoints	Up to Week 38
Percentage of Participants With Anti-Drug Antibodies	Baseline, Up to Week 38

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

Helpful Links

• Please use this form to submit your questions for a faster response: https://www.gene.com/contact-us/submit-medical-inquiry. Do not include or attach any medical records when emailing or completing the form. A nurse will respond within 24 business hours.

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2025
• Primary Completion (Estimated): April 19, 2027
• Study Completion (Estimated): October 8, 2027

Study Registration Dates

• First Submitted: August 15, 2025
• First Submitted That Met QC Criteria: August 15, 2025
• First Posted (Actual): August 22, 2025

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Arthritis, Rheumatoid; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: WA45846

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No