Clinical trial NCT06481202: A Safety and Pharmacokinetic Study of Complarate (Tocilizumab Biosimilar) and Actemra® in Healthy Volunteers
Official title: Double-blind Randomized Study of the Safety, Pharmacokinetics and Pharmacodynamics of the Drugs Complarate (JSC GENERIUM, Russia) and Actemra® (F. Hoffmann-La Roche Ltd., Switzerland) in Parallel Groups of Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: tocilizumab
humanized monoclonal antibodies
safety
pharmacokinetics
equivalence
biosimilar
IL-6 receptor
Lead sponsor: AO GENERIUM
Sponsor class: INDUSTRY
First posted: 2024-07-01
Enrollment: 43
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This is a randomized double-blind comparative parallel group study of the safety, pharmacokinetics and pharmacodynamics of Complarate and Actemra® in healthy volunteers. Participants received a single intravenous dose of tocilizumab 8 mg/kg. The follow up period was 43 days

Detailed description: Complarate (tocilizumab) is being developed as a biosimilar to the drug Actemra®, a concentrate for the preparation of a solution for infusion.

Tocilizumab is a recombinant humanized monoclonal antibody to the human interleukin-6 (IL-6) receptor from the immunoglobulin G1 (IgG1) subclass of immunoglobulins. Tocilizumab binds to and inhibits both soluble and membrane IL-6 receptors (sIL-6R and mIL-6R).

This I phase study is aimed to compare the pharmacokinetics and safety of the drugs Complarate and Actemra® after their single intravenous administration to healthy volunteers at a dose of 8 mg/kg. The study included healthy volunteers aged 18-45 years at the time of signing the informed consent form. The study included a screening period, single administration of study/comparator drug and a follow up period. Allocation of patients to treatment groups was carried out by randomization in a ratio of 1:1 to the study drug and comparator drug. 46 healthy volunteers (23 to the study drug group and 23 to the reference drug group) were randomized.

Eligibility criteria: Inclusion Criteria:

* Men aged 18 to 45 years (inclusive) at the time of signing the Informed Consent Form.
* The diagnosis is "healthy", concluded by a doctor-researcher based on the analysis of clinical and biochemical blood tests, urine tests, the results of a physical examination, measurements of vital signs, the results of electrocardiography and fluorography. In this case, the volunteer should not have any deviations in the tests carried out as part of the protocol.
* Conclusion of a dentist on the sanitation of the oral cavity.
* Availability of written informed consent obtained from the volunteer before the start of any procedures related to the study.
* Body weight from 60 to 90 kg inclusive.
* Body mass index 18.5-30 kg/m2 inclusive. Agreement to follow adequate methods of contraception for 3 months after administration of the study drug.
* Volunteers should not be donors of blood and its components 3 months before inclusion in the study and not become donors of blood and its products during the entire study and for 30 days after its completion.

Exclusion Criteria:

* Use of drugs based on monoclonal antibodies for 1 year before drug administration.
* Vaccination (with any vaccine) within 30 days before signing the informed consent and/or the need for vaccination during the study period.
* A history of an adverse drug reaction to any of the components of the study drug or a reference drug.
* History of an autoimmune disease.
* A history of a disease associated with the accumulation of immune complexes (including serum sickness).
* History of cancer.
* The presence of chronic diseases of the cardiovascular, bronchopulmonary (including bronchospastic diseases), neuroendocrine systems, as well as diseases of the gastrointestinal tract, liver, kidneys, hematopoietic, immune systems, and mental illnesses.
* Acute infectious diseases less than 4 weeks before signing the informed consent.
* Blood donation or blood loss (450 ml of blood or more) less than 3 months before the start of the study.
* Participation in clinical trials of drugs less than 3 months before signing the informed consent.
* Regular alcohol consumption exceeding 5 units. alcohol per week (where each unit is equal to 30 ml of ethyl alcohol) or anamnestic information about alcoholism, drug addiction, or drug abuse in the anamnesis.
* Positive test for the presence of alcohol in exhaled air.
* Smoking more than 5 cigarettes per day for 3 months before the study.
* Drug dependence and a positive urine test for the content of narcotic and potent drugs.
* Positive test for hepatitis B or C, HIV or syphilis.
* Unwillingness or inability to comply with the recommendations prescribed by this protocol.
* Any planned surgical intervention during the study period.
* Identification during screening of other diseases/conditions not listed above that, in the opinion of the doctor-researcher, prevent the inclusion of a volunteer in the study.

Primary outcomes:
measure: Pharmacokinetics: Area under the plasma concentration versus time curve (AUC)
timeFrame: day 43
measure: Pharmacokinetics: Peak Plasma Concentration (Cmax)
timeFrame: day 43
Secondary outcomes:
measure: Pharmacodynamics: Concentration of interleukine-6 (IL-6)
timeFrame: day 43
measure: Pharmacodynamics: Concentration of soluble interleukine-6 receptor (sIL-6R)
timeFrame: day 43
measure: Pharmacodynamics: Concentration of high-sensitivity C-reactive protein (hsCRP)
timeFrame: day 43
measure: Adverse events
timeFrame: day 43
measure: Immunogenicity
timeFrame: day 43
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Department of Clinical Research, Center for Clinical Drug Research
city: Moscow
country: Russian Federation
facility: Federal State Autonomous Educational Institution of Higher Education "First Moscow State Medical University named after I.M. Sechenov" of the Ministry of Health of Russia
Study officials:
affiliation: JSC GENERIUM
name: Oksana A. Markova, MD
role: STUDY_CHAIR
References: