A Safety, Pharmacokinetics and Pharmacodynamics Study of GNR-086 and Ilaris® in Healthy Volunteers

A Single-blind Randomized Parallel-group Comparative Study of the Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of GNR-086 and Ilaris® After a Single Subcutaneous Administration to Healthy Volunteers at a Dose of 150 mg

This is a randomized single-blind comparative parallel group study of the safety, pharmacokinetics and pharmacodynamics of GNR-086 and Ilaris® in healthy volunteers. Participants received a single subcutaneous dose of canakinumab 150 mg. The follow up period was 120 days.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: GNR-086; Biological: Ilaris®

Detailed Description

GNR-086 (canakinumab) is being developed as a biosimilar to the drug Ilaris®, a lyophilisate for the preparation of solution for subcutaneous administration.

Canakinumab is a recombinant human monoclonal antibody against human interleukine-1β that belongs to the immunoglobulin G1/k (IgG1/k) isotype subclass.

This study is intended for a comparative study of the safety, pharmacokinetics and pharmacodynamics of the drug GNR-086 and the reference drug Ilaris® for the purpose of registration of the drug - GNR-086 (JSC GENERIUM, Russia), 150 mg, lyophilisate for the preparation of solution for subcutaneous administration in the Russian Federation. 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. 105 patients (53 to the study drug group and 52 to the comparator drug group) were randomized.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 117556
    • State budgetary healthcare institution of the city of Moscow "City Clinic No. 2 of the Moscow Health Department"
  • Moscow, Russian Federation, 127473
    • Federal State Budgetary Educational Institution of Higher Education "Moscow State Medical and Dental University named after A.I. Evdokimov" of the Ministry of Health of the Russian Federation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Written informed consent to participate in the study, obtained from the volunteer before the start of any procedures related to the study;
• Men and women aged 18 to 45 years, inclusive, at the time of signing the informed consent form;
• Verified diagnosis "healthy" (the diagnosis "healthy" is established on the basis of a detailed medical history, in the absence of deviations from normal values during a clinical examination, including measurement of blood pressure, heart rate, respiratory rate, body temperature, as well as laboratory data studies, results of electrocardiography and fluorography);
• Body weight from 50 to 85 kg, body mass index from 18.5 to 28 kg/m2, inclusive.
• Agreement to adhere to adequate methods of contraception during the entire period of participation in the study or for 3 months after administration of the study or reference drug in case of early termination of participation in the study.

Exclusion Criteria:

• Severe chronic diseases, history of seizures;
• Acute infectious diseases less than 4 weeks before administration of the study or reference drug;
• Any history of chronic or recurrent infectious diseases;
• History of tuberculosis;
• Vaccination with any vaccine within 3 months before the administration of the study or reference drug or planned for the period of the volunteer's participation in the study;
• Compounded allergy history; history of hypersensitivity to the active substance or other components of the study or reference drug;
• Pregnancy or breastfeeding period;
• Special lifestyle (work at night, extreme physical activity);
• Deviations of vital signs: systolic pressure less than 100 mm Hg. Art. or more than 130 mm Hg. Art.; diastolic pressure less than 60 mm Hg. Art. or more than 90 mm Hg. Art.; heart rate less than 60 beats/min or more than 90 beats/min;
• Dehydration due to diarrhea, vomiting, or other cause within 24 hours prior to administration of the study or reference drug;
• Taking prescription medications within 28 days or 5 half-lives (whichever is longer) or taking over-the-counter medications/dietary supplements within 14 days prior to study or reference drug administration (occasional use of paracetamol at any time prior to study drug administration is acceptable) or reference drug);
• Blood donation or blood loss (450 ml of blood or more) less than 3 months before the administration of the study or reference drug and/or blood donation in any quantity planned for the period of the volunteer's participation in the study;
• Participation in clinical trials of medicinal products (less than 3 months or 5 half-lives from the study drug, whichever is longer) before administration of the investigational or reference drug of this study;
• Regular alcohol consumption exceeding 5 units. alcohol per week (where each unit is equal to 30 ml of ethyl alcohol or 325 ml of beer), or information about a history of alcoholism, drug addiction, or drug abuse;
• Positive test for the presence of alcohol in exhaled air;
• Smoking more than 5 cigarettes per day for 3 months before this study;
• Positive urine test for the content of narcotic and potent drugs;
• Positive test for hepatitis B, C, HIV or syphilis;
• Any surgical interventions planned during the period of participation in the study;
• Unwillingness or inability to comply with the requirements of this protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GNR-086 (JSC "GENERIUM", Russia); canakinumab biosimilar	Biological: GNR-086; The test drug GNR-086 was administered as a subcutaneous injection at a single dose of 150 mg.; Other Names: canakinumab
Active Comparator: Ilaris® (Novartis Pharma Stein AG, Switzerland); canakinumab	Biological: Ilaris®; The reference drug Ilaris® was administered as a subcutaneous injection at a single dose of 150 mg.; Other Names: canakinumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Area under the plasma concentration versus time curve (AUC)	Analysis of equivalence of area under concentration-time curve from time 0 (predose) extrapolated to infinity (AUC(0-∞) of GNR-086 and Ilaris®	Day 120
Pharmacokinetics: Peak Plasma Concentration (Cmax)	Analysis of equivalence of Cmax of GNR-086 and Ilaris®	Day 120

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics: interleukin-1β (IL-1β)	IL-1β concentration	Day 120
Pharmacodynamics: Area Under IL-1β Curve (AUC)	Area under the curve "Relative difference in total IL-1β concentration compared to baseline - time"	Day 120
Proportion of volunteers with adverse events (AE)	The Investigator will carefully monitor each subject throughout the study for any AEs (coded to preferred term and system organ class using the Medical Dictionary for Regulatory Activities [MedDRA])	Day 120
Immunogenicity	Antidrug antibodies (ADA) level	Day 120

Collaborators and Investigators

• Sponsor: AO GENERIUM
• Investigators: Study Chair: Oksana A. Markova, MD, JSC GENERIUM

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2022
• Primary Completion (Actual): March 17, 2023
• Study Completion (Actual): May 26, 2023

Study Registration Dates

• First Submitted: June 20, 2024
• First Submitted That Met QC Criteria: June 28, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Actual): July 1, 2024
• Last Update Submitted That Met QC Criteria: June 28, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics; pharmacodynamics; biosimilar; canakinumab; equivalence; humanized monoclonal antibodies; interleukine-1β
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAN-HVL-I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No