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

NCT05800327 | Active Not Recruiting Phase 3

• 1 other identifier: BCD-089-5/LUNAR
• Study Type: interventional
• Target: 261
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Levilimab; Ilsira; anti-IL-6R; IL-6 receptor inhibitors

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to day 71

• 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.

  Up to Week 24

Secondary Outcomes (34)

• RA remission (Stage 2, main period)

  Up to Week 24

• RA remission (Stage 2, main period)

  Up to Week 52

• PK endpoints (Stage 1)

  Up to Week 52

• PK endpoints (Stage 1)

  Up to Week 24

• PK endpoints (Stage 1)

  Up to Week 24

Study Arms (3)

LVL162 group

EXPERIMENTAL

Levilimab 162 mg SC QW plus placebo starting from Week 0.

Drug: Levilimab

LVL324 group

EXPERIMENTAL

Levilimab 324 mg SC Q2W plus placebo starting from Week 0.

Drug: Levilimab

LVL648 group

EXPERIMENTAL

levilimab 648 mg IV Q4W plus placebo starting from Week 0.

Drug: Levilimab

Interventions

Levilimab DRUG

Subcutaneous or intravenous injection of levilimab with placebo.

LVL162 group; LVL324 group; LVL648 group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Biocad: lead

Study Sites (1)

X7 Clinical Research

Saint Petersburg, Russia

Location

Related Publications (1)

• 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.

  PMID: 34586459 RESULT

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

levilimab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: April 5, 2023
• Study Start: December 7, 2022
• Primary Completion: September 1, 2024
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 5, 2023

Record last verified: 2023-03

Locations

RU (1)