A Study to Assess the Safety and Efficacy of Different Doses of ELV001 to Treat Active Rheumatoid Arthritis in Patients With an Inadequate Response to Methotrexate and Tumor Necrosis Factor Inhibition (START SYNERGY)

Exclusion Criteria

• •1. Class IV RA according to ACR revised response criteria.
• •2. Have been treated with more than 1 previous bDMARDs or tsDMARDs, excluding the current TNFi.
• •3. Has a secondary non-response to the TNFi due to anti-drug antibodies, as assessed by the Investigator.
• •4. Have a dose change of MTX or TNFi within the last 3 months before Baseline, or a dose change of hydroxychloroquine or oral prednisolone within the last 4 weeks before Baseline.
• •5. Have oral prednisone \> 7.5 mg/day equivalent or parenteral corticosteroids within the last 4 weeks before Baseline.
• •6. Have intra-articular corticosteroids within the last 4 weeks before Baseline.
• •7. Had any other csDMARD, bDMARD, or immunosuppressive drug in the last 2 months.
• •8. Had any cell depletion therapy (eg, rituximab) in the last 12 months.
• •9. Have QT interval corrected for heart rate (QTc) using Fridericia's correction (QTcF) \> 450 ms for males or QTcF \> 470 ms for females either at Screening or Baseline, based on safety 12-lead electrocardiogram (ECG). Have a Screening or Baseline ECG with second- or third-degree atrioventricular block, bundle branch block, arrhythmia (but not sinus arrhythmia or supraventricular premature beats), or illegible QT interval.
• •10. Have evidence of interstitial lung disease (ILD) based on either medical history, clinical signs and symptoms, imaging and/or lung function test, independently of the etiology of the ILD.
• •11. Have a condition which could interfere with drug absorption including but not limited to short bowel syndrome.
• •12. Have presence of 1 or more significant concurrent medical conditions, which could interfere with the treatment and/or the study per Investigator judgment, including but not limited to the following: poorly controlled diabetes or hypertension; chronic kidney disease stage IIIb, IV, or V; symptomatic heart failure (New York Heart Association class II, III, or IV); myocardial infarction or unstable angina pectoris within the past 12 months prior to randomization; severe chronic pulmonary disease (eg, requiring oxygen therapy); and major chronic inflammatory disease or connective tissue disease other than RA.
• •13. Have a history of chronic alcohol abuse, IV drug abuse or illicit drug abuse within 1 year before Screening.
• •14. Have a diagnosis or history of malignant disease, with the exceptions of basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
• •15. Have had any surgical procedure (except for minor surgery requiring local or no anesthesia and without any complications or sequelae) within 12 weeks prior to Screening, or any planned surgical procedure scheduled to occur during the study.
• •16. Have received a Bacillus Calmette-Guerin (BCG) vaccination or BCG treatment within 12 months of Screening; or received any other live vaccine(s) (ie, live attenuated) within 3 months of Screening, or intend to receive a live vaccine during the study.
• •17. Have had any of the following types of infection within 3 months of Screening or develops any of these infections before the randomization visit:
• •* Serious (requiring hospitalization, and/or parenteral antibiotic treatment),
• •* Opportunistic, as defined in (Winthrop et al. 2015) (note, Herpes zoster infection is considered active and ongoing until all vesicles are dry and crusted over),
• •* Chronic (duration of symptoms, signs, and/or treatment of 6 weeks or longer),
• •* Recurring (including, but not limited to herpes simplex, herpes zoster, recurring cellulitis, chronic osteomyelitis). Participants with recurrent nonserious infections such as cellulitis and uncomplicated orolabial and/or genital herpes may be enrolled at the discretion of the Investigator when deemed not to place participants at an increased risk of complications.
• •18. Have any of the following:
• •* Human immunodeficiency virus (HIV) infection,
• •* Current infection with hepatitis B virus (HBV) (ie, positive for hepatitis B surface antigen and/or polymerase chain reaction \[PCR\] positive for HBV DNA),
• •* Current infection with hepatitis C virus (HCV) (ie, positive for HCV RNA),
• •* Active tuberculosis (TB).
• •19. Have or have had latent TB infection (LTBI) that has not been treated with a complete course of appropriate therapy as defined by the World Health Organization (WHO) and/or the United States Centers for Disease Control and Prevention (CDC). Participants with LTBI who have been adequately treated are eligible for the study.
• •20. Current or recent acute active infection (ie, participants must have had no symptoms and/or signs of confirmed or suspected infection and must have completed any appropriate anti-infective treatment within 30 days of Baseline); or fever of 100.5°F (38°C) or above at Screening or Baseline.
• •21. Any other concurrent severe and/or uncontrolled medical, surgical or psychiatric and/or social condition which, in the view of the Investigator, could compromise the participant's safety or ability to participate in the study and make them unsuitable for participation.
• •22. Use of other investigational medicinal products within 12 weeks or at least 5 half-lives (whichever is longer) before study drug administration.
• •23. Women who are pregnant or breast-feeding or planning to become pregnant during the study.