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Rheumatoid ArthritisPhase 3NCT05800327

A Two-Stage Study of the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics and Immunogenicity of Various Doses of Levilimab When Administered Intravenously and Subcutaneously to Healthy Subjects and Subjects With Active Rheumatoid Arthritis

A Phase 3 study testing Levilimab in people with Rheumatoid Arthritis, run by Biocad at 1 site in Russia.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a two-stage study of efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of various doses of levilimab when administered intravenously and subcutaneously to healthy subjects and subjects with active rheumatoid arthritis resistant to methotrexate monotherapy. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
Levilimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
261 participants
Where
1 siteRussia
Study dates
7 Dec 2022to Dec 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Signed Informed Consent Form for participation in the study.
  • Malegender.
  • Age 18-45 inclusive at the time of signing the ICF.
  • Healthy status confirmed by the history, physical examination, and laboratory parameters.
  • The absence of a history and signs of alcohol abuse or substance addiction at the time of signing the ICF, and a negative alcohol saliva screening test in combination with a negative urine drug test.
  • The ability of the subject to follow the Protocol procedures, according to the Investigator.
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  • The readiness of the subject and their sexual partners with a childbearing potential to use reliable contraceptive measures from the date of signing the informed consent form throughout the study period and for 4 weeks after the administration of the investigational product. This requirement does not apply to the subjects and their partners who have undergone operative sterilization or the female partners of a subject who have been menopausal for more than 2 years.
  • Readiness not to drink alcohol within 24 hours prior to and 70 days after the administration of the investigational product.
  • Signed ICF for participation in the study.
  • Men and women aged ≥ 18 on the ICF signing day.
  • Rheumatoid arthritis that meets the ACR 2010 criteria, confirmed not less than 24 weeks before the ICF signing date. In the event that a subject has been diagnosed with rheumatoid arthritis in accordance with the ACR 1987 criteria, the physician-investigator must confirm the diagnosis in accordance with the ACR 2010 criteria during the screening period, with this information included in the primary documentation, if this has not been done previously and is not documented.
  • Methotrexate therapy during the 12 weeks prior to the ICF signing date.
  • Use of methotrexate at a stable dose during the 4 weeks prior to the ICF signing date (the methotrexate dose should be 15-25 mg per week, methotrexate dose of 10 mg may be used in case of intolerability/toxicity of a higher dose).
  • Failure of methotrexate when used over the 12 weeks before the ICF signing date (according to the Investigator).
  • Swollen joint count ≥ 6 (out of 66); tender joint count ≥ 6 (out of 68).
  • The presence of at least one of three criteria: 1) CRP ≥ 10 mg/L, 2) ESR ≥ 28 mm/h (Westergren method / capillary photometry), 3) morning stiffness that lasts longer than 45 minutes.
  • The ability of the subject to follow the Protocol procedures, according to the Investigator.
  • The readiness of the subject and their sexual partners with a childbearing potential to use reliable contraceptive measures from the date of signing the informed consent form throughout the study period and for 4 weeks after the administration of the last dose of the investigational product. This requirement does not apply to the subjects and their partners who have undergone operative sterilization or females who have been menopausal for more than 2 years.

Who cannot join

  • A history of treatment with the products containing monoclonal antibodies to interleukin 6 or its receptor.
  • A History of severe hypersensitivity reactions (angioneurotic edema, anaphylaxis, or multiple drug allergy).
  • Known allergy or intolerance to monoclonal antibody drugs (murine, chimeric, humanized, or fully human) or any other components of the investigational product.
  • Major surgery within 30 days before the signing of the ICF.
  • Severe infections (including those that required hospitalization or parenteral antibacterial, antiviral, antimycotic, or antiprotozoal agents) within 6 months before signing the ICF.
  • Use of systemic antibacterial, antiviral, antimycotic, or antiprotozoal agents within 2 months before signing the ICF.
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  • More than 4 episodes of respiratory infections over the past 6 months before signing the ICF.
  • Impossibility to insert a venous catheter for blood sampling (for example, due to skin disease at venipuncture sites).
  • A history of fever over 40 °C.
  • A history of increased levels of hepatic transaminases above 2.5 x ULN.
  • Epileptic seizures, a history of seizures.
  • Depression, suicidal ideations/attempts at the screening or in the history.
  • Regular oral or parenteral administration of any medicinal products, including over-the-counter drugs, vitamins and dietary supplements, within less than 2 weeks before signing the ICF.
  • Use of medicinal products, including over-the-counter drugs, with a pronounced effect on hemodynamics, liver function, etc. (barbiturates, omeprazole, cimetidine, etc.) within 30 days before signing the ICF.
  • Use of medicinal products that affect the immune status (cytokines and their inducers, glucocorticoid hormones, etc.) within 2 months before signing the ICF.
  • BCG vaccination, vaccination with live attenuated vaccines and with any other vaccines within 12, 8 and 4 weeks before signing the ICF, respectively, as well as during screening.
  • Standard laboratory and investigation abnormalities.
  • Smoking over 10 cigarettes a day.
  • Consumption of more than 10 units of alcohol per week (1 unit of alcohol is equivalent to ½ L of beer, 200 mL of wine or 50 mL of spirits) or a history of alcoholism, drug addiction, or drug abuse.
  • Donation of 450 mL or more of blood or plasma within 2 months prior to signing the ICF.
  • Participation in clinical trials of medicinal products within 2 months before signing the ICF or concurrent participation in other clinical trials.
  • Previous participation in the same clinical trial (excluding subjects who dropped out at screening and did not receive the IP).
  • Previous exposure to tocilizumab or other monoclonal antibodies to the interleukin 6 / interleukin 6 receptor.
  • Previous therapy with Janus kinase inhibitors.
  • Previous exposure to rituximab or other products that cause depletion or suppression of B cell activity.
  • Felty's syndrome (regardless of form).
  • The functional status of the subject is class IV according to the ACR 1991 classification.
  • Known allergy or intolerance to any component of the study drug.
  • Concomitant treatment with the following products:
  • the need for prednisolone or its equivalent at an oral dose of more than 10 mg/day;
  • the need for oral prednisolone or its equivalent at a dose of ≤10 mg/day if this dose was not stable during the last 4 weeks before signing the ICF (patients who received topical glucocorticoids can be included in the study);
  • the need for NSAID use if the NSAID dose was not stable during the last 4 weeks before signing the ICF (the patients who occasionally received NSAIDs for fever or allergic syndrome in case of intercurrent diseases can be included);
  • the use of alkylating agents at any time within 12 months before signing the ICF;
  • intra-articular administration of glucocorticoids within 4 weeks before signing the ICF;
  • vaccination with live or attenuated vaccines at any time within 8 weeks before signing the ICF;
  • the use of leflunomide within 8 weeks before signing the ICF;
  • therapy with TNF-α inhibitors or T cell co-stimulation blockers within 8 weeks before signing the ICF.
  • Patients with any of the following laboratory findings at screening:
  • the content of hemoglobin in the blood < 80 g/L;
  • the number of leukocytes in the blood < 3.0 × 109/L;
  • the number of platelets in the blood < 100 × 109/L;
  • the number of neutrophils in the blood < 2 × 109/L;
  • AST and ALT levels ≥ 1.5 × ULN approved in the laboratory;
  • serum creatinine ≥ 1.7 × ULN approved in the laboratory.
  • Positive pregnancy urine test in women at screening (the test is not performed in women who have been menopausal for at least 2 years or who have undergone operative sterilization; any of these conditions must be documented).
  • A confirmed diagnosis or a history of the severe immunodeficiency of any other nature.
  • Diagnosis of HIV infection, hepatitis B, C.
  • Diagnosis of tuberculosis, including a history of tuberculosis.
  • Latent forms of tuberculosis (positive Diaskintest® or positive result of the QuantiFERON®-TB Gold test or T-SPOT.TB test, in the absence of radiographic signs of pulmonary tuberculosis).
  • A history of or current herpes zoster.
  • Documented chickenpox within less than 30 days before signing the ICF.
  • The confirmed diagnosis of another chronic infection (for example, invasive mycoses, histoplasmosis, etc.), which can increase the risk of infectious complications in the opinion of the Investigator.

Trial locations and contacts

1 site in 1 country.

Russia1 site

  • X7 Clinical Research

    Saint Petersburg

Other trials in Russia

About this study

This is a two-stage study of efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of various doses of levilimab when administered intravenously and subcutaneously to healthy subjects and subjects with active rheumatoid arthritis resistant to methotrexate monotherapy.

Aim of the Stage 1 is to study the tolerability, safety, immunogenicity, and main pharmacokinetic and pharmacodynamic parameters of levilimab after its single subcutaneous or intravenous administration at ascending doses to healthy subjects.

Aim of the Stage 2 is to confirm the efficacy and safety of levilimab 648 mg IV Q4W in combination with methotrexate and levilimab 324 mg SC Q2W in combination with methotrexate in subjects with active rheumatoid arthritis, resistant to methotrexate monotherapy.

Read the detailed description

Stage 1: there are 3 dose levels and 5 cohorts. The subjects will be followed up for up to 71 days after the IP administration.

Stage 2: the main period of the study (Weeks 0-24) is blinded; study subjects will receive levilimab with placebo. At Week 24 the study will become open-label and all subjects will continue to receive levilimab. At week 28 patients who achieved the RA remission at week 24 will be switched to maintenance therapy of levilimab and will receive it through Week 52. Subjects who do not achieve remission at Week 24, will continue to receive levilimab from Week 28 to Week 52 inclusive corresponding to their treatment group.

Being tested
Levilimab
Keywords
Rheumatoid Arthritis, Levilimab, Ilsira, anti-IL-6R, IL-6 receptor inhibitors
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LevilimabDrug

    Subcutaneous or intravenous injection of levilimab with placebo.

Study groups in NCT05800327
Study groupRoleWhat they receive
LVL162 groupExperimentalLevilimab 162 mg SC QW plus placebo starting from Week 0.
Receives: Drug: Levilimab
LVL324 groupExperimentalLevilimab 324 mg SC Q2W plus placebo starting from Week 0.
Receives: Drug: Levilimab
LVL648 groupExperimentallevilimab 648 mg IV Q4W plus placebo starting from Week 0.
Receives: Drug: Levilimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety primary endpoint (Stage 1)

    To determine the safety profile of levilimab following its single subcutaneous or intravenous administration at ascending doses in healthy subjects.

    Measured: Up to day 71

  2. Low disease activity (Stage 2)

    Proportion of subjects with low activity of rheumatoid arthritis (DAS28-ESR <3.2) at Week 24 of the study in each treatment group.

    Measured: Up to Week 24

Secondary outcomes (34)

  1. RA remission (Stage 2, main period)

    Proportion of subjects who achieved RA remission according to DAS28-CRP (<2.6), DAS28-ESR (<2.6), CDAI (≤2.8), SDAI (≤3.3), and ACR/EULAR 2011

    Measured: Up to Week 24

  2. RA remission (Stage 2, main period)

    Proportion of subjects who achieved RA remission according to DAS28-CRP (<2.6), DAS28-ESR (<2.6), CDAI (≤2.8), SDAI (≤3.3), and ACR/EULAR 2011

    Measured: Up to Week 52

  3. PK endpoints (Stage 1)

    AUC0-1680

    Measured: Up to Week 52

  4. PK endpoints (Stage 1)

    AUC0-1680

    Measured: Up to Week 24

  5. PK endpoints (Stage 1)

    AUC0-∞

    Measured: Up to Week 24

  6. PK endpoints (Stage 1)

    AUC0-∞

    Measured: Up to Week 52

  7. PK endpoints (Stage 1)

    Cmax

    Measured: Up to Week 24

  8. PK endpoints (Stage 1)

    Cmax

    Measured: Up to Week 52

  9. PK endpoints (Stage 1)

    Cmin

    Measured: Up to Week 24

  10. PK endpoints (Stage 1)

    Cmin

    Measured: Up to Week 52

  11. PK endpoints (Stage 1)

    Tmax

    Measured: Up to Week 24

  12. PK endpoints (Stage 1)

    Tmax

    Measured: Up to Week 52

  13. PK endpoints (Stage 1)

    Tmin

    Measured: Up to Week 24

  14. PK endpoints (Stage 1)

    Tmin

    Measured: Up to Week 52

  15. PK endpoints (Stage 1)

    Vd

    Measured: Up to Week 24

  16. PK endpoints (Stage 1)

    Vd

    Measured: Up to Week 52

  17. PK endpoints (Stage 1)

    T½

    Measured: Up to Week 24

  18. PK endpoints (Stage 1)

    T½

    Measured: Up to Week 52

  19. PK endpoints (Stage 1)

    Kel

    Measured: Up to Week 24

  20. PK endpoints (Stage 1)

    Kel

    Measured: Up to Week 52

  21. PK endpoints (Stage 1)

    CL

    Measured: Up to Week 24

  22. PK endpoints (Stage 1)

    CL

    Measured: Up to Week 52

  23. ACR response (Stage 2, main period)

    Proportion of subjects who achieved ACR20, ACR50 and ACR70

    Measured: Week 24, 52

  24. Low disease activity (Stage 2, main period)

    Proportion of subjects with low rheumatoid arthritis activity according to DAS28-CRP (<3.2), DAS28-ESR (<3.2), CDAI (≤10), SDAI (≤11)

    Measured: Week 24, 52

  25. Changes in RA indexes (Stage 2, main period)

    Change in DAS28-CRP, DAS28-ESR, CDAI and SDAI from baseline

    Measured: Week 24, 52

  26. Moderate/good response according to the EULAR criteria (Stage 2)

    Proportion of subjects with moderate and good response according to the EULAR criteria at Week 24 and 52 compared with baseline values.

    Measured: Week 24, 52

  27. Change in the serum C-reactive protein concentration (Stage 2)

    Change in the serum C-reactive protein concentration from baseline

    Measured: Week 24, 52

  28. Change in ESR (Stage 2)

    Change in ESR from baseline

    Measured: Week 24, 52

  29. Change in the quality of life measured with SF-36 (Stage 2)

    Change in the quality of life according to the SF-36 questionnaire from baseline

    Measured: Week 24, 52

  30. Change in the quality of life measured with the EQ-5D-3L (Stage 2)

    Change in the quality of life according to the EQ-5D-3L questionnaire from baseline

    Measured: Week 24, 52

  31. Change in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) score (Stage 2)

    Change in the fatigue assessments according to the FACIT-F questionnaire from baseline

    Measured: Week 24, 52

  32. Change in functional activity (Stage 2)

    Change in the functional activity according to the HAQ-DI questionnaire from baseline

    Measured: Week 24, 52

  33. X-Ray assessment (Stage 2)

    Radiographic characterization of the affected joints at Week 24: change in mean modified total Sharp/van der Heijde score (mTSS).

    Measured: Week 24, 52

  34. Key Secondary PK endpoint (Stage 2)

    Ctrough geometric mean in each treatment group

    Measured: Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Apr 2023
  2. Study start7 Dec 2022
  3. Primary completionSep 2024 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
The study design assumes two sequential stages corresponding to Phase I and Phase III studies. Stage 1 This is an open-label, single-center, non-randomized cohort study of the safety and tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of single intravenous or subcutaneous levilimab injections administered to healthy subjects at ascending doses (modified 3+3 design). Stage 2 This is a randomized, comparative, double-blind, controlled clinical study to assess efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of levilimab when administered at repeated intravenous or subcutaneous doses in combination with methotrexate in subjects with active rheumatoid arthritis resistant to methotrexate monotherapy.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
261 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05800327
Sponsor's protocol ID
BCD-089-5/LUNAR
Status last verified
Mar 2023
First submitted
2 Feb 2023
Last updated
5 Apr 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA. The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study. Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.

    PubMed 34586459

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Levilimab in people with Rheumatoid Arthritis, run by Biocad at 1 site in Russia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 52 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety primary endpoint (Stage 1) (time frame: Up to day 71). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05800327, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2023.

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