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)

April 20, 2026 updated by: Elevara Medicines Limited

A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Investigate the Safety and Efficacy of ELV001 as Add-on Therapy in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate and Tumor Necrosis Factor Inhibition (START SYNERGY)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study has 4 study arms: placebo, 25mg, 75mg and 125mg. The study includes a 4 weeks screening period, a double blind placebo controlled period (weeks 0 to 12), a treatment extension (weeks 12 to 24) and a 4 week safety follow-up.

Study Type

Interventional

Enrollment (Estimated)

180

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
    • Cape Town
      • Panorama, Cape Town, South Africa, 7500
        • Recruiting
        • Panorama Medical Center
        • Contact:
        • Principal Investigator:
          • Dr Ingrid Clara Louw
    • Capetown
      • Pinelands, Capetown, South Africa, 7405
        • Recruiting
        • The Arthritis Clinical Trial Centre
        • Contact:
        • Principal Investigator:
          • Dr. Cathy Spargo
      • Somerset West, Capetown, South Africa, 7500
        • Recruiting
        • Winelands Medical Research Centre - Somerset West (Dr Francois Bouwer INC)
        • Contact:
        • Principal Investigator:
          • Dr Francois Bouwer
    • Gauteng
      • Germiston, Gauteng, South Africa, 1401
        • Recruiting
        • CRISMO Research Centre - Bertha Gxowa Hospital
        • Contact:
        • Principal Investigator:
          • Dr Mpoti Belina Seboka
      • Pretoria, Gauteng, South Africa, 0002
        • Recruiting
        • Netcare Jakaranda Hospital Suite 102
        • Contact:
        • Principal Investigator:
          • Dr. Elsa Margaretha van Duuren
    • KwaZulu-Natal
      • Durban, KwaZulu-Natal, South Africa, 4319
        • Recruiting
        • Netcare Umhlanga Medical Centre
        • Contact:
        • Principal Investigator:
          • Dr. Asokan Niaidoo
    • Western Cape
      • Stellenbosch, Western Cape, South Africa, 7600
        • Recruiting
        • Winelands Medical Research Centre
        • Contact:
        • Principal Investigator:
          • Dr. Helmuth Reuter
  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85032
        • Recruiting
        • Arizona Arthritis & Rheumatology Associates
        • Contact:
        • Principal Investigator:
          • Dr. Daniel Kreutz
      • Glendale, Arizona, United States, 85306
        • Recruiting
        • Arizona Arthritis & Rheumatology Associates
        • Contact:
        • Principal Investigator:
          • Dr. Nehad Solomon
      • Tucson, Arizona, United States, 85704
        • Recruiting
        • Arizona Arthritis & Rheumatology Associates
        • Contact:
        • Principal Investigator:
          • Dr. Romy Cabacungan
    • California
      • Tustin, California, United States, 92780
        • Recruiting
        • Solace Clinical Research - Populace Health (Network)
        • Contact:
        • Principal Investigator:
          • Dr. Christine Kornu, MD
    • Colorado
      • Denver, Colorado, United States, 80230
        • Recruiting
        • Denver Arthritis Clinic
        • Contact:
        • Principal Investigator:
          • Dr. Christopher R Antolini, MD
    • Florida
      • Boca Raton, Florida, United States, 33486
        • Recruiting
        • Rheumatology Associates of South Florida-Clinical Research Inc - Cliniverse Research (Network)
        • Contact:
        • Principal Investigator:
          • Dr. Shawn Baca
      • Margate, Florida, United States, 33063
        • Recruiting
        • Prophase, LLC - Clinitiative Health Research (Network)
        • Contact:
        • Principal Investigator:
          • Dr. Renan Amador
      • Miami, Florida, United States, 33126
        • Recruiting
        • Millennium Medical Research LLC - Clinitiative Health Research (Network)
        • Contact:
        • Principal Investigator:
          • Dr. Ramon Moreda
      • Miami Beach, Florida, United States, 33016
        • Recruiting
        • Floridian Clinical Research, LLC - Clinitiative Health Research (Network)
        • Contact:
        • Principal Investigator:
          • Dr. Christopher Mesa
      • South Miami, Florida, United States, 33143
        • Recruiting
        • Bioresearch Partner - Cliniverse Research (Network)
        • Contact:
        • Principal Investigator:
          • Dr. Olga Kromo, MD
    • Louisiana
      • Lake Charles, Louisiana, United States, 70605
        • Recruiting
        • Accurate Clinical Research Inc (SMO/ Network)
        • Contact:
        • Principal Investigator:
          • Dr. Enrique A Mendez, MD
    • Michigan
      • Lansing, Michigan, United States, 48911
        • Recruiting
        • Great Lakes Center of Rheumatology
        • Contact:
        • Principal Investigator:
          • Dr. Joshua June, DO
    • North Carolina
      • Charlotte, North Carolina, United States, 28262
        • Recruiting
        • DJL Clinical Research PLLC (Network) cIRB
        • Contact:
        • Principal Investigator:
          • Dr. Emily Jane Box
      • Wilmington, North Carolina, United States, 28401
        • Recruiting
        • Carolina Arthritis Associates - Cliniverse Research (Network)
        • Contact:
        • Principal Investigator:
          • Dr. Mark D Harris
    • Pennsylvania
      • Duncansville, Pennsylvania, United States, 16635
        • Recruiting
        • Altoona Arthritis & Osteoporosis Center
        • Contact:
        • Principal Investigator:
          • Dr. Alan J Kivitz, MD, CPI
      • Wyomissing, Pennsylvania, United States, 19610
        • Recruiting
        • Pennsylvania Regional Center for Arthritis & Osteoporosis Research
        • Contact:
        • Principal Investigator:
          • Dr. Greg Emkey, MD
    • Texas
      • Baytown, Texas, United States, 77521
        • Recruiting
        • Accurate Clinical Management, LLC. - Accurate Clinical Research Inc (SMO/ Network)
        • Contact:
        • Principal Investigator:
          • Dr. Sabeen Najam, MD
      • Houston, Texas, United States, 77089
        • Recruiting
        • Accurate Clinical Research Inc (SMO/ Network)
        • Contact:
        • Principal Investigator:
          • Dr. Philip Waller, MD
      • Jackson, Texas, United States, 11372
        • Recruiting
        • Heights Rheumatology and Aesthetics - ES Clinical Research Group Network
        • Contact:
        • Principal Investigator:
          • Dr. Enelda M Agosto-Colon
      • Red Oak, Texas, United States, 78666
        • Recruiting
        • Epic Medical Research-Red Oak
        • Contact:
        • Principal Investigator:
          • Dr. Sunny Patel, MD
      • Tomball, Texas, United States, 77375
        • Recruiting
        • DM Clinical Research (Network)
        • Contact:
        • Principal Investigator:
          • Dr. Shaikh Arif Ali, MD
      • Tomball, Texas, United States, 77377
        • Recruiting
        • DM Clinical Research (Network)
        • Contact:
        • Principal Investigator:
          • Dr. Qaiser Rehman

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Provided written informed consent to participate to the study and are able and willing to adhere to the study protocol.
  2. Male or female, 18 to 75 years of age, at the time of signing the informed consent.
  3. Body mass index (BMI) between 18.5 and 32.0 kg/m2 and minimum weight of 50 kg at the Screening Visit.
  4. 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.
  5. 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.
  6. Have C-reactive protein (CRP) ≥ upper limit of normal (ULN) at Screening.
  7. Have adequate hematologic function at Screening AND at Baseline.
  8. Have adequate liver and renal function at Screening.
  9. 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.
  10. 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.
  11. 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.

  12. Female participants of childbearing potential must:

    1. Have a negative serum pregnancy test at Screening and a negative urine pregnancy test within 24 hours prior to first dosing.
    2. Use highly effective contraception from signing the informed consent until at least 90 days after the last dosing.
    3. Not donate ova from signing the informed consent until at least 90 days after the last dosing.
  13. 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

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Placebo from week 0 to week 12, then ELV001 75mg or 125mg per day from week 12 to week 24.
Experimental: ELV001 25 mg QD
Drug: ELV001 25 mg
25mg from week 0 to week 12 then ELV001 75mg or 125mg per day from week 12 to week 24
Experimental: ELV001 75 mg QD
Drug: ELV001 75 mg
75mg from week 0 to week 24
Experimental: ELV001 125 mg QD
Drug: ELV001 125 mg
125mg from week 0 to week 24

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Disease activity score 28- C-reactive protein between Baseline and Week 12.
Time Frame: From Baseline to 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of TEAEs, SAEs, and AESIs.
Time Frame: Up to 32 weeks
Up to 32 weeks
Incidence and severity of SUSARs
Time Frame: Up to 32 weeks
Up to 32 weeks
Change from Baseline in 12-lead ECG parameters (including QTcF)
Time Frame: From baseline to week 28
From baseline to week 28
Change from Baseline in vital signs (Respiratory Rate)
Time Frame: Baseline to week 28
Respiratory Rate [breaths per minute (bpm)]
Baseline to week 28
Change from Baseline in laboratory parameters (hematology, biochemistry, coagulation, and urinalysis).'
Time Frame: Baseline to week 28
Baseline to week 28
Percentage of participants reaching remission and low disease activity as defined by Disease activity score 28- C-reactive protein at Week 12 and at Week 24.
Time Frame: From Baseline to week 12 and week 24
From Baseline to week 12 and week 24
Percentage of participants reaching ACR20/ACR50/ACR70 at Week 12 and at Week 24
Time Frame: From Baseline to week 12 and week 24
From Baseline to week 12 and week 24
Change from Baseline to Week 12 and to Week24 in swollen joint count, tender joint count
Time Frame: From Baseline to week 12 and week 24
66 Swollen Joint Count (SJC) and 68 Tender Joint Count (TJC): Joint Count will be assessed by an independent joint assessor, and the same assessor will be used throughout all visits of the study
From Baseline to week 12 and week 24
Change From baseline to Weeks12 and 24 in Short form health survey36,
Time Frame: From Baseline to week 12 and week 24
Short form health survey36: Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning.
From Baseline to week 12 and week 24
Assessment of any correlation between dose and disease activity scores.
Time Frame: Baseline to week 28
Baseline to week 28
Plasma drug and metabolite concentrations - area under the curve (AUC)
Time Frame: baseline to week 28
Pharmacokinetics - AUC
baseline to week 28
Plasma drug and metabolite concentration - maximum concentration (Cmax)
Time Frame: baseline to week 28
Pharmacokinetics - Cmax
baseline to week 28
Change from Baseline in vital signs (Body Temperature)
Time Frame: Baseline to week 28
Body Temperature (Celsius)
Baseline to week 28
Change from Baseline in vital signs (Blood Pressure)
Time Frame: Baseline to week 28
Blood Pressure: Systolic [Millimeters of mercury(mmHg)], Diastolic [Millimeters of mercury(mmHg)],
Baseline to week 28
Change from Baseline in vital signs (Heart Rate)
Time Frame: Baseline to week 28
Heart rate (Per minute)
Baseline to week 28
Change from Baseline to Week 12 and to Week 24 in simplified disease activity index (SDAI).
Time Frame: From Baseline to week 12 and week 24
Total scores ranging from 0 to 100. Higher scores indicate greater disease activity.
From Baseline to week 12 and week 24
Change from Baseline to Week 12 and to Week 24 in Clinical disease activity index (CDAI).
Time Frame: From Baseline to week 12 and week 24
Total scores ranging from 0 to 76. Higher scores indicate greater disease activity.
From Baseline to week 12 and week 24
participant's global assessments: disease activity (VAS),and arthritis pain (VAS)
Time Frame: From Baseline to week 12 and week 24
participant's global assessments: disease activity (VAS): Results will be expressed in millimeters measured to the crossing point on the VAS scale.
From Baseline to week 12 and week 24
Change from Baseline to Week 12 and to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI).
Time Frame: From Baseline to week 12 and week 24
Scores for each of the 8 functional domains will be averaged to calculate the functional disability index.
From Baseline to week 12 and week 24
Functional Assessment of Chronic illness Therapy
Time Frame: From Baseline to week 12 and week 24
The sum of all responses is combined to give a FACIT-Fatigue score range from 0 to 52 with higher scores indicating less fatigue.
From Baseline to week 12 and week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Elevara Medicines Limited

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 18, 2026

Primary Completion (Estimated)

April 15, 2027

Study Completion (Estimated)

March 31, 2028

Study Registration Dates

First Submitted

December 11, 2025

First Submitted That Met QC Criteria

February 6, 2026

First Posted (Actual)

February 13, 2026

Study Record Updates

Last Update Posted (Actual)

April 23, 2026

Last Update Submitted That Met QC Criteria

April 20, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Other Study ID Numbers

  • ELV001-201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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