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

• Register: ClinicalTrials.gov
• Last refreshed on: 29 November 2021
• Main ID: NCT03455842
• Date of registration: 22/02/2018
• Prospective Registration: No
• Primary sponsor: Biocad
• Public title: The BCD-089 (aIL6R) in Patients With Active Rheumatoid Arthritis AURORA
• Scientific 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
• Date of first enrolment: February 1, 2018
• Target sample size: 105
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03455842
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Belarus, Russian Federation

Contacts

• Name: Roman Ivanov, PhD
• Affiliation: Biocad

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Signed informed consent

2. Males and females aged 18 - 80 years, at IC signing date.

3. Diagnosis of rheumatoid arthritis, according to ACR 2010 criteria, at least for 6
month prior to IC signing date.

4. Active rheumatoid arthritis at IC signing date.

5. Therapy with methotrexate for at least 3 month prior to IC signing date.

6. Stable dose of methotrexate (10-25 mg/week) for 4 weeks prior to IC signing date.

7. Persistent activity of RA despite methotrexate (provided by Sponsor) therapy within
screening period (4-6weeks).

8. 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)

9. 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).

10. Patients ability to follow the protocol procedures (according to PI opinion)

11. 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)

Exclusion Criteria:

- 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).

- 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:

1. Uncontrolled diabetes mellitus;

2. Severe, uncontrolled hypertonia;

3. 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.);

4. 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



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Seropositive RA

Intervention(s)

Drug: placebo

Biological: BCD-089, 162 mg, s/c, q2w

Biological: BCD-089, 162 mg, s/c, qw

Primary Outcome(s)

ACR20 [Time Frame: week 12]

Secondary Outcome(s)

RA remission [Time Frame: week 24, week 36, week 48, week 52]

X-ray signs of RA [Time Frame: week52]

Pharmacokinetics of BCD-089 [Time Frame: week 0 - week 12]

ACR50 [Time Frame: week 4, week 8, week 16, week 24, week 36, week 48, week 52]

Pharmacodynamics of BCD-089 [Time Frame: week 0 - week 12]

ACR70 [Time Frame: week 4, week 8, week 16, week 24, week 36, week 48, week 52]

Low RA activity [Time Frame: week 4, week 8, week 12, week 16, week 24, week 36, week 48, week 52]

Secondary ID(s)

BCD-089-2

Source(s) of Monetary Support

Please refer to primary and secondary sponsors