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Seropositive RAPhase 2AURORANCT03455842

The BCD-089 (aIL6R) in Patients With Active Rheumatoid Arthritis

A Phase 2 study testing BCD-089, 162 mg, s/c, qw and BCD-089, 162 mg, s/c, q2w in people with Seropositive RA, run by Biocad at 4 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The study is Phase II randomized, double-blind, placebo-controlled clinical trial to evaluate efficacy and safety, pharmacokinetics and pharmacodynamics of 2 dosing regimens (qw and q2w, s/c) of monoclonal antibody to IL6R (BCD-089) in patients with active rheumatoid arthritis and inadequate response to methotrexate. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Seropositive RA
What is being tested?
BCD-089, 162 mg, s/c, qw and BCD-089, 162 mg, s/c, q2w
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
105 participants
Where
4 sitesin 2 countries
Study dates
1 Feb 2018to 22 Oct 2019
Phase
Phase 2
Are there results?
None posted in the registry

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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent
  • Males and females aged 18 - 80 years, at IC signing date.
  • Diagnosis of rheumatoid arthritis, according to ACR 2010 criteria, at least for 6 month prior to IC signing date.
  • Active rheumatoid arthritis at IC signing date.
  • Therapy with methotrexate for at least 3 month prior to IC signing date.
  • Stable dose of methotrexate (10-25 mg/week) for 4 weeks prior to IC signing date.
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  • Persistent activity of RA despite methotrexate (provided by Sponsor) therapy within screening period (4-6weeks).
  • Patients, with following parameters of laboratory investigations:
  • Hemoglobin ≥ 80 g/l;
  • White blood cells ≥ 3,0×109/l;
  • Platelets ≥ 100×109/l;
  • Neutrophils ≥ 2×109/l;
  • ALT and AST < 1,5 × UNL (according to the local / central laboratory normal values)
  • Serum creatinine < 1,7 × UNL (according to the local / central laboratory normal values)
  • Negative urine pregnancy test for women at screening (only for women with childbearing potential - not applied to women at menopause for at least 2 years or surgically sterilized).
  • Patients ability to follow the protocol procedures (according to PI opinion)
  • Patient and his/her sexual partner with childbearing potential are ready to use reliable contraception, starting at the date of IC sign, within the study period and 4 weeks after the last dose of investigational drug administration. (Not applied to participants/sexual partners who surgically sterilized, and women at menopause for more than 2 years). Reliable contraception considered as 1 barrier method and one of the following: spermicides, oral contraception or intrauterine devices)

Who cannot join

  • 1. History of therapy with tocilizumab or other monoclonal antibodies to IL6R / IL6.
  • 2. History of therapy with rituximab or other B-cell depleting medicines. 3. Felty's syndrome (any form). 4. ACR1991 functional status IV. 5. Low disease activity of rheumatoid arthritis (DAS28-CRP(4) < 3,2). 6. Known allergy or intolerance of any investigational drug/placebo ingredients.
  • 7. Concomitant medication including any of the following:
  • Requirement > 10 mg / day of oral prednisolone (or equivalent);
  • Requirement < 10 mg / day of oral prednisolone (or equivalent), if the dose was not stable for 4 weeks prior the date of informed consent sign (it is allowed to include patients on topical steroids);
  • Requirement of NSAID, if dose was not stable for 4 weeks prior the date of informed consent sign (it is allowed to include patients received NSAID occasionally to treat intercurrent fever or allergy).
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  • Intake of alkalizing agents at any time during 12 month prior the date of IC sign.
  • Intraarticular administration of steroids within 4 month prior the date of IC sign
  • Vaccination with live or attenuated vaccines at any time during 8 weeks preceding the date of IC sign 8. Leflunomide intake within 8 weeks prior the date of IC sign. 9. Therapy with TNF inhibitors, JAK-inhibitors, T-lymphocyte co-stimulation blockers within 2 month prior to the date of IC sign.
  • 10. Diagnosis or history of severe immunodeficiency. 11. HIV, HCV, HBV, Syphilis. 12. Diagnosis or history of tuberculosis. 13. Latent TB (positive Diaskin test® or QuantiFERON®-TB Gold or T-SPOT.TB or Mantoux/PPD with lack of TB signs on chest X-ray).
  • 14. It is allowed to include patients with inconclusive Diaskin test® or QuantiFERON®-TB Gold or T-SPOT.TB or Mantoux/PPD, providing that TB has been ruled out (and documented) by TB-specialist (Phtisyatrician) 15. It is allowed to include patients with positive Mantoux/PPD with no signs of TB on chest X-ray, providing that Diaskin test® or QuantiFERON®-TB Gold or T-SPOT.TB was additionally made with negative results and TB has been ruled out (and documented) by TB-specialist (Phtisyatrician) 16. History of Herpes Zoster. 17. Documented chicken pox within 30 days prior to IC sign 18. Diagnosis of any other chronic infection (sepsis, invasive mycosis, histoplasmosis etc.), which may increase the risk of infectious adverse events.
  • 19. Any acute infection or chronic infection flare within 30 days prior to informed consent sign, which may increase (according to the PI opinion) the risk of infectious adverse events.
  • 20. Severe infections (required hospitalization, systemic antimicrobial/antifungal/antiviral treatment) within 6 months prior to date of IC sign.
  • 21. Systemic antimicrobial, antifungal, antiviral or anthelminthic medication within 2 months prior to fate of IC date.
  • 22. More than 4 cases of acute respiratory infections within 6 month prior to IC date.
  • 23. Major surgical interventions within 30 days prior to IC date or planned surgical intervention within the period of the study participation.
  • 24. History of seizures. 25. History of depression, suicidal ideation/behavior. 26. Diverticulosis or diverticulitis. 27. Known history of alcohol or drug abuse, or signs of alcohol/drug dependence at present time, which according to the PI opinion could interfere with RA treatment or reduce compliance.
  • 28. Any other documented conditions which increase the risk of AEs development or may interfere with symptoms of RA (masking, increasing or changing) or induce clinical symptoms or laboratory abnormalities similar to RA:
  • Uncontrolled diabetes mellitus;
  • Severe, uncontrolled hypertonia;
  • Presence or history of inflammatory joint disease other than RA (ankylosing spondylitis, gout, psoriatic arthritis, Lyme disease) or any other systemic autoimmune disease (including lupus, Crohn's disease, ulcerative colitis, scleroderma, inflammatory myopathy, mixed connective tissue disease, autoimmune overlap syndrome, fibromyalgia etc.);
  • Any history of malignancy, excluding cured basal cell carcinoma / cervical cancer in situ (complete remission for 5 years); cured basal cell skin carcinoma (5 years complete remission), cured ductal breast cancer (5 years complete remission);
  • Decompensated liver or kidney diseases;
  • Unstable angina pectoris;
  • Chronic heart failure, class III-IV according to NYHA;
  • Myocardial infarction, within 1 year prior to IC sign;
  • History of organ transplantation;
  • History of Quincke edema; History of any significant respiratory diseases, including COPD, asthma or bronchiectasis disease;
  • Decompensated respiratory failure;
  • History of multiple sclerosis, Devic's disease, or Guillain-Barre syndrome;
  • Any neurological disease with motor or sensory functions impairment. 29. Pregnancy, current or planned in less than 8 weeks after study completion or breastfeeding.
  • 30. Simultaneous participation in other clinical trials or participation in other clinical trials with 3 month prior to IC signing date or history of participation it current clinical study (excluding patients dropped out at screening).

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

Russia3 sites

  • Chelyabinsk Regional Clinical hospital

    Chelyabinsk

  • Kazan State Medical University

    Kazan'

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

    Saint Petersburg

Other trials in Russia

Belarus1 site

  • 1st City Clinical Hospital

    Minsk

Other trials in Belarus

About this study

Official title: International Multicenter Comparative Randomized Double-blind Placebo-controlled Clinical Study of Efficacy and Safety of BCD-089 in Different Dosing Regimens in Patients With Active Rheumatoid Arthritis

The study is Phase II randomized, double-blind, placebo-controlled clinical trial to evaluate efficacy and safety, pharmacokinetics and pharmacodynamics of 2 dosing regimens (qw and q2w, s/c) of monoclonal antibody to IL6R (BCD-089) in patients with active rheumatoid arthritis and inadequate response to methotrexate.

Read the detailed description

IL-6 is a new potential therapeutic target which plays important role in pathogenesis of several autoimmune disorders including rheumatoid arthritis. BCD-089 is a novel fully human monoclonal antibody against the interleukin-6 receptor developed by JCS BIOCAD (Russia) which is successfully passed phase I clinical study. Fixed dose of 162 mg was chosen for evaluation in phase II clinical trial. Comparisons in terms of efficacy, safety, PK/PD will be made for every week and every other week dosing for 54 weeks. W0-W12, planed as blinded, "main" period of the study, consists of three arms (n=35, each) - 2 study arms and placebo arm and served to test the hypothesis of superiority of BCD-089 to placebo. W12-W54, planned as "open" period of the study and served to evaluate long-therm safety and efficacy of BCD-089 in patients with active rheumatoid arthritis.

Conditions
Seropositive RA
Being tested
BCD-089, 162 mg, s/c, qw, BCD-089, 162 mg, s/c, q2w, placebo

What participants receive

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

  • BCD-089, 162 mg, s/c, qwBiological

    Subcutaneous injections of anti-IL6R every week

  • BCD-089, 162 mg, s/c, q2wBiological

    Subcutaneous injections of anti-IL6R every other week

  • placeboDrug

    Subcutaneous injections of placebo every week, until week 12. Thereafter subcutaneous injections of anti-IL6R every other week

Study groups in NCT03455842
Study groupRoleWhat they receive
BCD-089 weeklyExperimentalNot described
Receives: Biological: BCD-089, 162 mg, s/c, qw
BCD-089 biweeklyExperimentalNot described
Receives: Biological: BCD-089, 162 mg, s/c, q2w
PlaceboPlacebo comparatorNot described
Receives: Drug: placebo

What is being measured

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

  1. ACR20

    Measured: week 12

Secondary outcomes (17)

  1. ACR50

    Measured: week 4, week 8, week 16, week 24, week 36, week 48, week 52

  2. ACR70

    Measured: week 4, week 8, week 16, week 24, week 36, week 48, week 52

  3. Low RA activity

    DAS28-CRP(4)<3.2

    Measured: week 4, week 8, week 12, week 16, week 24, week 36, week 48, week 52

  4. Low RA activity

    SDAI = 11 or less

    Measured: week 4, week 8, week 12, week 16, week 24, week 36, week 48, week 52

  5. Low RA activity

    CDAI = 10 or less

    Measured: week 4, week 8, week 12, week 16, week 24, week 36, week 48, week 52

  6. RA remission

    According to the ACR/EULAR 2011 remission criteria

    Measured: week 24, week 36, week 48, week 52

  7. X-ray signs of RA

    Measured: week52

  8. Pharmacokinetics of BCD-089

    Area Under the BCD-089 Plasma Concentration Versus Time Curve [AUC0-last]

    Measured: week 0 - week 12

  9. Pharmacokinetics of BCD-089

    Peak Plasma Concentration [Cmax]

    Measured: week 0 - week 12

  10. Pharmacokinetics of BCD-089

    Minimum Plasma Concentration [Cmin]

    Measured: week 0 - week 12

  11. Pharmacokinetics of BCD-089

    Time to Maximum Plasma Concentration [Tmax]

    Measured: week 0 - week 12

  12. Pharmacokinetics of BCD-089

    Time to Minimum Plasma Concentration [Tmin]

    Measured: week 0 - week 12

  13. Pharmacokinetics of BCD-089

    Accumulation Ratio [AR]

    Measured: week 0 - week 12

  14. Pharmacodynamics of BCD-089

    Plasma concentration of CRP

    Measured: week 0 - week 12

  15. Pharmacodynamics of BCD-089

    Plasma concentration of Interleukin-6

    Measured: week 0 - week 12

  16. Pharmacodynamics of BCD-089

    Plasma concentration of soluble receptor of interleukin-6

    Measured: week 0 - week 12

  17. Pharmacodynamics of BCD-089

    Plasma concentration of tumor necrosis factor - alpha

    Measured: week 0 - week 12

Timeline

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

  1. First posted7 Mar 2018
  2. Study start1 Feb 2018
  3. Primary completion31 Dec 2018
  4. Study completion22 Oct 2019

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
105 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03455842
Sponsor's protocol ID
BCD-089-2
Acronym
AURORA
Status last verified
Dec 2019
First submitted
22 Feb 2018
Last updated
18 Nov 2021
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Mazurov V.I., Korolev M.A., Prystrom A.M., Kunder E.V., Soroka N.F., Kastanayan A.A., Povarova T.V., Plaksina T.V., Antipova O.V., Kretchikova D.G., Smakotina S.A., Tciupa O.A., Puntus E.V., Raskina T.A., Shilova L.N., Kropotina T.V., Nesmeyanova O.B., Popova T.A., Vinogradova I.B., Linkova Yu.N., Dokukina E.A., Plotnikova A.V., Pukhtinskaia P.S., Zinkina-Orikhan A.V., Eremeeva A.V., Lutckii A.A. Effectiveness and safety of levilimab in combination with methotrexate in treatment of patients with active rheumatoid arthritis resistant to methotrexate monotherapy (double-blinded randomized placebo controlled phase III clinical study SOLAR). Modern Rheumatology Journal. 2021;15(4):13-23. https://doi.org/10.14412/1996-7012-2021-4-13-23

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BCD-089, 162 mg, s/c, qw and BCD-089, 162 mg, s/c, q2w in people with Seropositive RA, run by Biocad at 4 sites in 2 countries.

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 17 inclusion and 32 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: finished, as of the sponsor's last update on 18 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Russia, Belarus. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

ACR20 (time frame: week 12). 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 NCT03455842, 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 18 Nov 2021.

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