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)

NCT07409103 | Recruiting Phase 2 FDA Drug

• 1 other identifier: ELV001-201
• Study Type: interventional
• Target: 180
• Locations: 2 countries
• Sites: 29

Brief Summary

This is a Phase 2 randomized, double-blind, placebo-controlled study with a total duration of 32 weeks from Screening to End-of-Study (EOS) Visit. Approximately 180 participants are planned to be enrolled. The number of participants can be extended to maximally 220 to account for dropouts during the study.

Conditions

Active Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Change in Disease activity score 28- C-reactive protein between Baseline and Week 12.

  Change in Disease Activity Score (Disease activity score 28- C-reactive protein) from Baseline to Week 12, comparing placebo with the highest ELV001 dose group, Score less than 2.6 indicates disease in remission, score more than 5.1 indicates very active disease

  From Baseline to week 12

Secondary Outcomes (20)

• Incidence and severity of TEAEs, SAEs, and AESIs.

  Up to 32 weeks

• Incidence and severity of SUSARs

  Up to 32 weeks

• Change from Baseline in 12-lead ECG parameters (including QTcF)

  From baseline to week 28

• Change from Baseline in vital signs (Respiratory Rate)

  Baseline to week 28

• Change from Baseline in laboratory parameters (hematology, biochemistry, coagulation, and urinalysis).'

  Baseline to week 28

Study Arms (4)

ELV001 25 mg QD

EXPERIMENTAL

Drug: ELV001 25 mg

ELV001 75 mg QD

EXPERIMENTAL

Drug: ELV001 75 mg

ELV001 125 mg QD

EXPERIMENTAL

Drug: ELV001 125 mg

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

ELV001 75 mg DRUG

75mg from week 0 to week 24

ELV001 75 mg QD

ELV001 125 mg DRUG

125mg from week 0 to week 24

ELV001 125 mg QD

Placebo DRUG

Placebo from week 0 to week 12, then ELV001 75mg or 125mg per day from week 12 to week 24.

Placebo

ELV001 25 mg DRUG

25mg from week 0 to week 12 then ELV001 75mg or 125mg per day from week 12 to week 24

ELV001 25 mg QD

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provided written informed consent to participate to the study and are 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 and the presence of ≥ 3 swollen joints (based on 66 joint count) and ≥ 3 tender joints (based on 68 joint count) at 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.
• Have adequate liver and renal function at Screening.
• 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 must:
• Have a negative serum pregnancy test at Screening and a negative urine pregnancy test within 24 hours prior to first dosing.
• Use highly effective contraception from signing the informed consent until at least 90 days after the last dosing.
• Not donate ova from signing the informed consent until at least 90 days after the last dosing.

You may not qualify if:

• Class IV RA according to ACR revised response criteria.
• Have been treated with more than 1 previous bDMARDs or tsDMARDs, excluding the current TNFi.
• 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 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 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.
• 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 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.

Sponsors & Collaborators

• Elevara Medicines Limited: lead

Study Sites (29)

Arizona Arthritis & Rheumatology Associates

Gilbert, Arizona, 85032, United States

RECRUITING

Arizona Arthritis & Rheumatology Associates

Glendale, Arizona, 85306, United States

RECRUITING

Arizona Arthritis & Rheumatology Associates

Tucson, Arizona, 85704, United States

RECRUITING

Solace Clinical Research - Populace Health (Network)

Tustin, California, 92780, United States

RECRUITING

Denver Arthritis Clinic

Denver, Colorado, 80230, United States

RECRUITING

Rheumatology Associates of South Florida-Clinical Research Inc - Cliniverse Research (Network)

Boca Raton, Florida, 33486, United States

RECRUITING

Prophase, LLC - Clinitiative Health Research (Network)

Margate, Florida, 33063, United States

RECRUITING

Millennium Medical Research LLC - Clinitiative Health Research (Network)

Miami, Florida, 33126, United States

RECRUITING

Floridian Clinical Research, LLC - Clinitiative Health Research (Network)

Miami Beach, Florida, 33016, United States

RECRUITING

Bioresearch Partner - Cliniverse Research (Network)

South Miami, Florida, 33143, United States

RECRUITING

Accurate Clinical Research Inc (SMO/ Network)

Lake Charles, Louisiana, 70605, United States

RECRUITING

Great Lakes Center of Rheumatology

Lansing, Michigan, 48911, United States

RECRUITING

DJL Clinical Research PLLC (Network) cIRB

Charlotte, North Carolina, 28262, United States

RECRUITING

Carolina Arthritis Associates - Cliniverse Research (Network)

Wilmington, North Carolina, 28401, United States

RECRUITING

Altoona Arthritis & Osteoporosis Center

Duncansville, Pennsylvania, 16635, United States

RECRUITING

Pennsylvania Regional Center for Arthritis & Osteoporosis Research

Wyomissing, Pennsylvania, 19610, United States

RECRUITING

Accurate Clinical Management, LLC. - Accurate Clinical Research Inc (SMO/ Network)

Baytown, Texas, 77521, United States

RECRUITING

Accurate Clinical Research Inc (SMO/ Network)

Houston, Texas, 77089, United States

RECRUITING

Heights Rheumatology and Aesthetics - ES Clinical Research Group Network

Jackson, Texas, 11372, United States

RECRUITING

Epic Medical Research-Red Oak

Red Oak, Texas, 78666, United States

RECRUITING

DM Clinical Research (Network)

Tomball, Texas, 77375, United States

RECRUITING

DM Clinical Research (Network)

Tomball, Texas, 77377, United States

RECRUITING

Panorama Medical Center

Panorama, Cape Town, 7500, South Africa

RECRUITING

The Arthritis Clinical Trial Centre

Pinelands, Capetown, 7405, South Africa

RECRUITING

Winelands Medical Research Centre - Somerset West (Dr Francois Bouwer INC)

Somerset West, Capetown, 7500, South Africa

RECRUITING

CRISMO Research Centre - Bertha Gxowa Hospital

Germiston, Gauteng, 1401, South Africa

RECRUITING

Netcare Jakaranda Hospital Suite 102

Pretoria, Gauteng, 0002, South Africa

RECRUITING

Netcare Umhlanga Medical Centre

Durban, KwaZulu-Natal, 4319, South Africa

RECRUITING

Winelands Medical Research Centre

Stellenbosch, Western Cape, 7600, South Africa

RECRUITING

Study Design

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

Study Record Dates

• First Submitted: December 11, 2025
• First Posted: February 13, 2026
• Study Start: February 18, 2026
• Primary Completion (Estimated): April 15, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (7); US (22)