Study of the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of BCD-180 in Patients With Axial Spondyloarthritis (LEVENTA)

NCT06333210 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: BCD-180-3
• Study Type: interventional
• Target: 421
• Locations: 2 countries
• Sites: 32

Brief Summary

The aim of the study is to evaluate the efficacy, safety, immunogenicity, pharmacokinetics and pharmacodynamics of a fixed dose of study drug (BCD-180) in comparison with placebo in patients with active axial spondyloarthritis (axSpA). The study will include HLA-B27+ patients with radiographic (r-axSpA) and non-radiographic (nr-axSpA) who had no response to prior therapy with non-steroidal anti-rheumatic drugs (NSAIDs), have not received biologic disease-modifying anti-rheumatic drugs (bDMARDs) or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), and subjects with insufficient efficacy and/or loss of efficacy on bDMARDs and/or tsDMARDs.

Conditions

Axial Spondyloarthritis

Keywords

biologics; axial spondyloarthritis; monoclonal antibodies; TRBV9

Outcome Measures

Primary Outcomes (2)

• Proportion of subjects who achieved ASAS40 among bDMARDs and tsDMARD-naive subjects

  Ratio of patients who developed a decrease in ankylosing spondylitis assessment score (ASAS) by 40% or more

  [Time Frame: week 24]

• Proportion of subjects who achieved ASAS40 among bDMARDs and/or tsDMARD-experienced subjects

  Ratio of patients who developed a decrease in ankylosing spondylitis assessment score (ASAS) by 40% or more

  [Time Frame: week 24]

Secondary Outcomes (35)

• Proportion of subjects who achieved ASAS40 among subjects with r-axSpA

  [Time Frame: week 24]

• Proportion of subjects who achieved ASAS40 among subjects with nr-axSpA

  [Time Frame: week 24]

• Proportion of subjects with the ASDAS-CRP <1.3

  [Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156]

• Proportion of subjects with the ASDAS-CRP ≥1.3 - <2.1

  [Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156]

• Proportion of subjects with the ASDAS-CRP ≥2.1 - ≤3.5

  [Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156]

Study Arms (5)

bDMARDs and/or tsDMARD experienced subjects, BCD-180 group

EXPERIMENTAL

Subjects in this arm will receive a fixed dose of BCD-180 infusions

Biological: anti-TRBV9 monoclonal antibody infusions

bDMARDs and/or tsDMARD experienced subjects, Placebo group

PLACEBO COMPARATOR

Subjects in this arm will receive Placebo infusions till the assessment of the primary endpoint and then will be switched to BCD-180 infusions

Other: Placebo infusions

bDMARDs and tsDMARD-naive subjects, BCD-180 group

EXPERIMENTAL

Subjects in this arm will receive a fixed dose of BCD-180 infusions and subcutaneous injections of placebo to maintain blindness of adalimumab therapy till the assessment of the primary endpoint, thereafter subjects will receive only BCD-180 infusions

Biological: anti-TRBV9 monoclonal antibody infusions; Other: Placebo subcutaneous injection

bDMARDs and tsDMARD-naive subjects, Placebo group

PLACEBO COMPARATOR

Subjects in this arm will receive Placebo infusions and subcutaneous injections of placebo to maintain blindness of adalimumab therapy till the assessment of the primary endpoint, thereafter subjects will be switched to BCD-180 infusions

Other: Placebo infusions; Other: Placebo subcutaneous injection

bDMARDs and tsDMARD-naive subjects, Adalimumab group

ACTIVE COMPARATOR

Subjects in this arm will receive subcutaneous injections of adalimumab and infusions of placebo till the assessment of the primary endpoint, thereafter subjects will be switched to BCD-180 infusions

Other: Placebo infusions; Drug: Adalimumab subcutaneous injection

Interventions

anti-TRBV9 monoclonal antibody infusions BIOLOGICAL

infusions

Also known as: BCD-180 infusions

bDMARDs and tsDMARD-naive subjects, BCD-180 group; bDMARDs and/or tsDMARD experienced subjects, BCD-180 group

Placebo infusions OTHER

infusions

bDMARDs and tsDMARD-naive subjects, Adalimumab group; bDMARDs and tsDMARD-naive subjects, Placebo group; bDMARDs and/or tsDMARD experienced subjects, Placebo group

Adalimumab subcutaneous injection DRUG

subcutaneous injection

bDMARDs and tsDMARD-naive subjects, Adalimumab group

Placebo subcutaneous injection OTHER

subcutaneous injection

bDMARDs and tsDMARD-naive subjects, BCD-180 group; bDMARDs and tsDMARD-naive subjects, Placebo group

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form for participation in the study.
• Men and women aged \>18 years of age at the time of signing the Informed Consent Form for participation.
• Positive test result for HLA-B27.
• \. Presence of r-axSpA OR nr-axSpA according to the criteria provided below:
• r-axSpA: axSpA diagnosis meets the ASAS 2009 criteria subject to the presence of radiographic signs of sacroiliitis according to the modified New York criteria (van der Linden et al. 1984) according to the central review. Subjects with an established diagnosis of ankylosing spondylitis according to the modified New York criteria may also be included in the study (van der Linden et al. 1984).
• nr-axSpA: axSpA diagnosis meets ASAS 2009 criteria in the absence of radiographic signs of sacroiliitis according to the modified New York criteria (van der Linden et al. 1984) according to the central review.
• Active disease at the screening and the randomization visit diagnosed based on both criteria:
• ASDAS-CRP ≥2.1
• assessment of the severity of back pain ≥4 on the NRS (BASDAI, question No. 2).
• For subjects with nr-axSpA: presence of objective MRI signs of sacroiliitis (according to ASAS/OMERACT) as assessed by the central review AND/OR based on hsCRP level \>1.5 ULN at screening.
• For subjects with r-axSpA: hsCRP level ˃1.5 ULN at screening.
• Duration of back pain ≥3 months, age \<45 years at the onset of the axSpA-associated back pain.
• Meeting at least one of the following criteria based on the Investigator's assessment:
• Inadequate response to therapy with NSAIDs defined as insufficient response to therapy with NSAIDs at therapeutic doses for at least 4 weeks, or insufficient response to therapy with two NSAIDs at the maximum permitted dose with the total duration of therapy of at least 4 weeks;
• Contraindications for therapy with NSAIDs;

You may not qualify if:

• Refusal to take NSAIDs for the treatment of axSpA for any subjective reasons that do not have a clinical justification.
• Use of the following medicines/procedures:
• at any time before signing the ICF: total lymphoid irradiation;
• at any time before signing the ICF: bone marrow transplantation, including stem and hematopoietic cell transplantation for any indications;
• at any time before signing the ICF: splenectomy;
• within 8 weeks before signing the ICF: treatment with immunoglobulins;
• within 12 months before signing the ICF: use of immunosuppressants. Exception: glucocorticoids. A subject receiving glucocorticoids may be included in the study provided that the daily dose of glucocorticoids is ≤10 mg/day (calculated with reference to prednisolone) and was stable for at least 4 weeks prior to the Randomization Visit.
• within 4 weeks before signing the ICF and during the screening period: use of synthetic DMARDs and thiopurines, including, but not limited to: 6-mercaptopurine, azathioprine, and others.
• Exception: the medicinal products listed below if their dose was stable for 4 weeks before signing the ICF and during the screening period:
• oral or parenteral methotrexate at a dose ≤25 mg/week, therapy shall be started at least 8 weeks before signing the ICF;
• aminosalicylic acid and its derivatives, including sulfasalazine, at a dose not exceeding 3 g/day, provided that therapy was started at least 8 weeks before signing the ICF. Subjects with inflammatory bowel disease (IBD) may be treated with topical 5-aminosalicylic acid at therapeutic doses;
• intra-articular and paraspinal glucocorticoids within 4 weeks prior to the Randomization Visit, intramuscular glucocorticoids within 2 weeks prior to the Randomization Visit;
• use of alkylating agents at any time within 12 months prior to signing the ICF;
• BCD-180 administration at any time before signing the ICF.
• Vaccination with any vaccines within 12 weeks prior to signing the ICF.

Sponsors & Collaborators

• Biocad: lead

Study Sites (32)

1St City Clinical Hospital, Minsk

Minsk, Belarus

Location

State Institution "Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology"

Minsk, Belarus

Location

KGBU "City Hospital No. 4 named after N.P. Gull, Barnaul"

Barnaul, Russia

Location

Chelyabinsk Regional Clinical hospital

Chelyabinsk, Russia

Location

Regional State Budgetary Healthcare Institution "Irkutsk City Clinical Hospital 1"

Irkutsk, Russia

Location

Republican Clinical Diagnostic Center of the Ministry of Health of the Udmurt Republic

Izhevsk, Russia

Location

Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan

Kazan', Russia

Location

State Autonomous Healthcare Institution "Kuzbass Clinical Emergency Hospital named after M. A. Podgorbunsky"

Kemerovo, Russia

Location

Federal State Budgetary Institution "Pirogov National Medical Surgical Center" of the Ministry of Health of the Russian Federation

Moscow, Russia

Location

Federal State Budgetary Scientific Institution "Research Institute of Rheumatology named after V.A. Nasonova"

Moscow, Russia

Location

State Budgetary Healthcare Institution of Moscow City "City Clinical Hospital 15 named after O.M. Filatov of the Moscow City Health Department"

Moscow, Russia

Location

State Budgetary Healthcare Institution of Moscow City Clinical Hospital 1 named after N.I. Pirogov of the Moscow City Health Department

Moscow, Russia

Location

State Budgetary Higher Vocational Education Institution I.M. Sechenov First Moscow State Medical University

Moscow, Russia

Location

State Budgetary Healthcare Institution "Center of Allergology and Immunology" of Kabardino-Balkarian Republic

Nal'chik, Russia

Location

State Budgetary Healthcare Institution of the Nizhny Novgorod Region "Nizhny Novgorod Regional Clinical Hospital named after N. A. Semashko"

Nizhny Novgorod, Russia

Location

Federal State Budgetary Scientific Institution "Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences"

Novosibirsk, Russia

Location

Budgetary healthcare institution of the Omsk region "Regional clinical hospital"

Omsk, Russia

Location

State Budgetary Healthcare Institution of Perm Krai "Order of Honour" Perm Regional Clinical Hospital "

Perm, Russia

Location

Federal State Budgetary Educational Institution of Higher Education "Rostov State Medical University" of the Ministry of Health of the Russian Federation

Rostov-on-Don, Russia

Location

Clinical Rheumatology Hospital №25

Saint Petersburg, Russia

Location

Federal State Budgetary Educational Institution of Higher Education "St. Petersburg State University"

Saint Petersburg, Russia

Location

Federal State Budgetary Institution "Almazov National Medical Research Center" of the Ministry of Health of the Russian Federation

Saint Petersburg, Russia

Location

North-Western State Medical University n.a. I.I.Mechnikov

Saint Petersburg, Russia

Location

State Budgetary Healthcare Institution "Samara Regional Clinical Hospital named after V.D. Seredavin"

Samara, Russia

Location

Private Healthcare Institution "Clinical Hospital" RD-Medicine "of the city of Saratov

Saratov, Russia

Location

Private Healthcare Institution "Clinical Hospital" RD-Medicine "of Smolensk

Smolensk, Russia

Location

Federal State Budgetary Educational Institution of Higher Education "Siberian State Medical University"

Tomsk, Russia

Location

Republican Clinical Hospital named after G. G. Kuvatov

Ufa, Russia

Location

State Healthcare Institution Ulyanovsk Regional Clinical Hospital

Ulyanovsk, Russia

Location

State Healthcare Institution "City Clinical Emergency Hospital 25"

Volgograd, Russia

Location

State Budgetary Healthcare Institution of the Yaroslavl Region "Clinical Hospital named after N.A. Semashko"

Yaroslavl, Russia

Location

State Autonomous Healthcare Institution of the Sverdlovsk Region "City Clinical Hospital 14 Ekaterinburg"

Yekaterinburg, Russia

Location

MeSH Terms

Conditions

Axial Spondyloarthritis

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Study Officials

• Arina Zinkina-Orikhan, PhD, MD

  Director of Clinical Development Department, BIOCAD

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 20, 2024
• First Posted: March 27, 2024
• Study Start: December 25, 2023
• Primary Completion: December 1, 2024
• Study Completion (Estimated): February 1, 2028
• Last Updated: June 3, 2024

Record last verified: 2024-05

Locations

BE (2); RU (30)