The BCD-132-5/LIBERIUS clinical study will evaluate the efficacy and safety of divozilimab in patients who:
Reached the age of 18 years.
Have a confirmed diagnosis of systemic scleroderma.
Have a modified skin score of 10 to 20 (patients with a score of 7-9 may be included in case of active disease progression).
Have a FVC (forced vital capacity) ≥ 40% of the due value.
Have IgG antibodies to varicella zoster virus (human herpesvirus) based on the results of a screening examination.
Agree to use reliable methods of contraception throughout the study and for 6 months after it.
Reached the age of 14 years.
Have a confirmed diagnosis of systemic scleroderma.
Age ≥16 years: have a diagnosis of systemic scleroderma according to the 2013 ACR/EULAR classification1 and a modified skin score of 10 to 20 points (patients with a score of 7–9 may be included if the disease is actively progressing).
Age ≥14, <16 years: have a diagnosis of systemic scleroderma according to the 2007 PRES/ACR/EULAR criteria2.
Have a FVC (forced vital capacity) ≥ 40% of the due value.
Have IgG antibodies to varicella zoster virus (human herpesvirus) based on the results of a screening examination.
Agree to use reliable methods of contraception throughout the study and for 6 months after it.
Reached the age of 14 years.
Have a confirmed diagnosis of systemic scleroderma.
Age ≥16 years: have a diagnosis of systemic scleroderma according to the 2013 ACR/EULAR classification1 and a modified skin score of 10 to 20 points (patients with a score of 7–9 may be included if the disease is actively progressing).
Age ≥14, <16 years: have a diagnosis of systemic scleroderma according to the 2007 PRES/ACR/EULAR criteria2.
Have a FVC (forced vital capacity) ≥ 40% of the due value.
Have IgG antibodies to varicella zoster virus (human herpesvirus) based on the results of a screening examination.
Agree to use reliable methods of contraception throughout the study and for 6 months after it.
This study has exclusion criteria (precluding participation in this clinical study), which will all be explained to the potential participant by the study doctor. In particular, the exclusion criteria are:
Induced scleroderma.
Presence of silicone implants or prostheses.
Presence of digital ulcers with signs of infection or indications for amputation of any extent.
A history of severe allergic reactions (anaphylactic shock or multiple drug allergy, or evidence of severe allergic or anaphylactic reactions to humanized and/or murine monoclonal antibodies).
A total IgG level 2 or more times lower than the LLN (lower limit of normal).
Blood chemistry abnormalities at screening:
serum creatinine level >2 ULN (upper limit of normal);
Positive HIV1 or HIV2 test, syphilis, active hepatitis B, active hepatitis C.
Positive SARS-CoV2-RNA PCR test at screening or COVID-19 less than 6 months before signing the informed consent form.
FEV1/FVC <0.7 and FEV1 (forced expiratory volume in 1 second) <50% at screening.
Grade 3-4 pulmonary hypertension at screening; severe heart failure, severe uncontrolled hypertension; unstable angina, acute or chronic pulmonary heart disease; a history of myocardial infarction, ischemic stroke, transient ischemic attacks less than 1 year before signing the informed consent form.
Scleroderma renal crisis, including a history thereof.
Use of anti-CD20 and anti-CD19 monoclonal antibodies within 1.5 years prior to screening.
Basic therapy at doses exceeding:
Methotrexate up to 25 mg/week.
Azathioprine up to 150 mg/day.
Hydroxychloroquine up to 400 mg/day.
Mycophenolate mofetil/sodium up to 2 g/day.
Glucocorticoids at a dose of more than 10 mg/day (prednisolone equivalent) within two weeks prior to signing the informed consent form.
Use of the following drugs:
cyclophosphamide, tocilizumab, abatacept, leflunomide, tacrolimus, tofacitinib, cyclosporine A, potassium para-aminobenzoate, nintedanib, pirfenidone, vasopressors for 6 months before signing the informed consent form.
Use of a combination of mycophenolate mofetil/sodium + methotrexate.
A malignancy, or a history thereof, with the exception of cured basal cell carcinoma, cervical cancer in situ, and cured solid tumors with a remission of more than 5 years.
Barrett’s esophagus with high-grade dysplasia.
Pregnancy, breast-feeding, or planned pregnancy at any time during the study.
A history of alcohol or drug addiction.
The BCD-132–5/LIBERIUS study takes place in study centers of different cities in the Russian Federation: Kazan, Ulyanovsk, Saint Petersburg, Novosibirsk, Izhevsk, Rostov-on-Don, Smolensk, Omsk, Moscow, Chelyabinsk, Vladimir, Nizhny Novgorod, Saratov, Kemerovo, Ufa, Barnaul and others.
You can ask questions about participation in the clinical study and request contact information about study centers using a special form on the site ct.biocad.ru.
The study doctor will tell the potential participant about other eligibility criteria and contraindications for participation in this clinical study. The potential participant should read the full information about the study and consult the study doctor and/or attending physician.
Authorization of the Ministry of Health of the Russian Federation for this clinical study, No. 562 dated September 21, 2022, and the list of approved study centers have been published in the State Register of Medicines.
ACR/EULAR 2013 Classification Criteria for Systemic Sclerosis.
PRES/ACR/EULAR 2007 are the 2007 diagnostic criteria of juvenile systemic sclerosis.