Phase 2 Randomized Double-Blind Placebo-Controlled Study of ELV001 Add-On Therapy in Patients With Active Rheumatoid Arthritis Inadequate to Methotrexate and TNF Inhibition

Trial ID: 2025-524005-32-00
Protocol: ELV001-201
Sponsor: Elevara Medicines Limited

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Diseases & Conditions

Rheumatoid arthritis

Objectives

The primary objective is to evaluate the efficacy of ELV001 as add-on therapy in active rheumatoid arthritis, which is clinically relevant for determining whether the treatment can improve disease control in patients with an inadequate response to standard therapy. The secondary objectives are to assess the safety and tolerability of ELV001, to examine its impact on disease activity, and to evaluate plasma pharmacokinetics in participants with active rheumatoid arthritis.

Participants

The trial included 85 participants with rheumatoid arthritis. The population comprised male and female participants aged 18 to 75 years with adult-onset disease of at least 6 months’ duration and active disease at screening. Participants were required to have a body mass index between 18.5 and 32.0 kg/m2 and a minimum weight of 50 kg. Selection was based on clinical and laboratory criteria, including current treatment with methotrexate and a TNF inhibitor for specified durations, partial response to the TNF inhibitor, and stable background therapy when applicable. Additional eligibility criteria included adequate hematologic, hepatic, and renal function, as well as use of appropriate contraception for participants of childbearing potential and male participants. No specific information was provided regarding diet, physical activity, or other lifestyle habits.

Plans and Procedures

A rheumatoid arthritis study is a Phase 2, randomized, double-blind, placebo-controlled trial of ELV001 as add-on therapy to standard-of-care in participants with active disease and an inadequate response to methotrexate and tumor necrosis factor inhibition. The trial is planned to run from 2026-03-10 to 2028-12-31, with participant involvement expected to extend from screening through the Week 24 end-of-study visit. The screening visit is used to assess eligibility criteria, including disease activity, prior and current background therapy, laboratory parameters, and reproductive safety requirements where applicable. Eligible participants undergo baseline assessment and then receive study treatment under blinded conditions, with follow-up visits conducted to evaluate efficacy, safety, vital signs, electrocardiography, laboratory values, and patient- and physician-reported outcomes. The end-of-study visit occurs at Week 24 and is used for final efficacy and safety assessments. Early termination may occur if eligibility criteria are no longer met, if protocol requirements are not followed, or if discontinuation is required for safety reasons, including adverse events or clinically significant abnormalities.

Treatment

The investigational treatment was ELV001, administered as an oral capsule at a dose of 125 mg. The study evaluated ELV001 as add-on therapy in participants with active rheumatoid arthritis and inadequate response to methotrexate and tumor necrosis factor inhibition. Administration was performed according to the study dosing schedule specified in the trial protocol.

The non-experimental treatment was placebo, provided as ELV100 Placebo Tablets. The study was randomized and double-blind, with placebo used as the comparator treatment. Treatment assignment and dosing compliance were monitored within the clinical trial framework.

Efficacy

Efficacy will be assessed by the change in DAS28-CRP from Baseline to Week 12. The primary comparison will be between placebo and the highest dose group. Additional efficacy assessments will include the percentage of participants reaching remission and low disease activity as defined by DAS28-CRP at Week 12 and Week 24, the percentage of participants reaching ACR20, ACR50, and ACR70 at Week 12 and Week 24, and changes from Baseline to Week 12 and Week 24 in swollen joint count, tender joint count, physician’s global assessment of disease activity measured by VAS, serum CRP levels, SDAI, and CDAI. Changes from Baseline to Week 12 and Week 24 will also be evaluated for participant’s global assessment of disease activity by VAS, participant’s global assessment of arthritis pain by VAS, participant’s assessment of physical function by HAQ-DI, SF-36, and FACIT-Fatigue Questionnaire. Dose response relationship on Disease Activity Scores will be assessed.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Have the minimum level of literacy required to provide written informed consent to participate in the study, have an adequate understanding of the study requirements and study protocol, and be able and willing to adhere to the study protocol.
Male or female, 18 to 75 years of age, at the time of signing the informed consent.
Body mass index (BMI) between 18.5 and 32.0 kg/m2 and minimum weight of 50 kg at the Screening Visit.
Have a diagnosis of adult onset RA and fulfill the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria (Aletaha et al. 2010) for at least 6 months prior to Screening.
Have active RA defined by a DAS28-CRP ≥ 3.2 at Screening.
Have ≥ 3 swollen joints (based on 66 joint count) and ≥ 3 tender joints (based on 68 joint count) at both Screening and Baseline. The distal interphalangeal joint should be evaluated but not included in the total count to determine eligibility.
Have C-reactive protein (CRP) ≥ upper limit of normal (ULN) at Screening.
Have adequate hematologic function at Screening AND at Baseline as defined below (repeat measurement of borderline values permitted): • absolute neutrophil count ≥ 2.5 × 109/L (≥ 2.5 × 103/μL or ≥ 2.5 GI/L), • platelet count ≥ 100 × 109/L (≥ 100 × 103/μL or ≥ 100 GI/L), • hemoglobin level ≥ 10.0 g/dL, • lymphocyte count > 500 cells/μL (> 0.50 × 103/μL or > 0.50 GI/L), • total leukocyte count ≥ 3.0 × 109/L (≥ 3.0 × 103/μL or ≥ 3.0 GI/L).
Have adequate liver and renal function at Screening as defined below (repeat measurement of borderline values permitted): • serum creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels ≤ 2 × ULN • total bilirubin level (TBL) and alkaline phosphatase (ALP) ≤ 1.5 × ULN • estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 (calculated by site laboratory or using the CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] formula).
Are currently treated with MTX (methotrexate) with folic acid supplementation according to local standard-of-care. The maximum dose of MTX is 25 mg/week for oral use and 20 mg/week for parenteral use. The minimum dose is 15 mg/week, except in case of intolerance or side effects when doses of 7.5 mg/week or above are acceptable. MTX should have been used for at least 6 months, of which at least 3 months at a stable dose.
Are currently treated with a TNFi for at least 6 months, of which at least 3 months at a stable dose. Participants should have demonstrated a partial response to the TNFi, as evidenced by the Investigator or treating physician based on DAS28-CRP, SDAI, CDAI or any other measure of disease activity as per local treatment guidelines.
The following therapies for RA are permitted during the study, if the dose is stable for ≥ 4 weeks prior to Screening: hydroxychloroquine up to 400 mg/day, oral prednisone ≤ 7.5 mg daily or equivalent corticosteroid dose. Prior treatment with other csDMARDs, bDMARDs, or tsDMARD is permitted as long as these treatments have been stopped at least 2 months prior to Screening, with exception of cell depleting therapies (eg, rituximab), which should have been stopped at least 12 months prior to Screening.
Female participants of childbearing potential (see definition in Section 5.4) must: a. Have a negative serum pregnancy test at Screening and a negative urine pregnancy test within 24 hours prior to first dosing. b. Use highly effective contraception from signing the informed consent until at least 90 days after the last dosing. c. Not donate ova from signing the informed consent until at least 90 days after the last dosing.
Male participants must use condoms and partners of childbearing potential must use highly effective contraception until at least 90 days after the last dosing. Male participants must not donate sperm until at least 90 days after the last dosing.

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Exclusion Criteria

Class IV RA according to the Steinbrocker Functional classification.
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).
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.
Have been treated with more than 1 previous bDMARDs or tsDMARDs, excluding the current TNFi. If bDMARDS or tsDMARDs within the same class have been switched for non-medical reasons (eg, switching between an originator and a biosimilar TNFi because of administrative issues such as access or reimbursement policies), this will be counted as a single previous treatment.
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.
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.
Use of other investigational medicinal products within 12 weeks or at least 5 half-lives (whichever is longer) before study drug administration.
Women who are pregnant or breast-feeding or planning to become pregnant during the study.
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.
Has a secondary non-response to the TNFi due to anti-drug antibodies, as assessed by the Investigator.
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.
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.
Have oral prednisone > 7.5 mg/day equivalent or parenteral corticosteroids within the last 4 weeks before Baseline.
Have intra-articular corticosteroids within the last 4 weeks before Baseline.
Had any other csDMARD, bDMARD, or immunosuppressive drug in the last 2 months.
Had any cell depletion therapy (eg, rituximab) in the last 12 months.
Have a condition which could interfere with drug absorption including but not limited to short bowel syndrome.
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.
Have a history of chronic alcohol abuse, IV drug abuse or illicit drug abuse within 1 year before Screening.
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.
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.
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.
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.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Bulgaria	Not Yet Recruiting	10 Mar 2026	24
Czechia	Not Yet Recruiting	10 Mar 2026	16
Hungary	Not Yet Recruiting	10 Mar 2026	8
The Netherlands	Not Yet Recruiting	10 Mar 2026	—
Poland	Not Yet Recruiting	10 Mar 2026	24
Spain	Not Yet Recruiting	10 Mar 2026	17
Netherlands	—	—	6