Study of Pharmacokinetics, Pharmacodynamics and Safety Assessment of GNR-044 (JSC GENERIUM, Russia) and Xolair® (NAP)

An Open-label, Randomized, in Parallel Groups Comparative Study of Pharmacokinetics, Pharmacodynamics, Immunogenicity and Safety of Omalizumab (JSC "GENERIUM", Russia) and Xolair® ("Novartis Pharma AG", Switzerland) After Single-dose Subcutaneous Administration in Healthy Volunteers at 150 mg

An open-label, randomized, in parallel groups comparative study of pharmacokinetics, pharmacodynamics, immunogenicity and safety of GNR-044 (JSC "GENERIUM", Russian Federation) and Xolair® ("Novartis Pharma AG", Switzerland) after single subcutaneous administration in healthy volunteers at 150 mg

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: Omalizumab (JSC "GENERIUM", the Russian Federation); Biological: Xolair® (Novartis Pharma AG, Switzerland)

Detailed Description

There is an increasing incidence of bronchial asthma (BA) and other allergic diseases around the world. Bronchial asthma suffers from 4 to 10% of the world population, in Russian Federation, the incidence of BA across the adult population ranges from 2.2 to 5-7%, in the child population is about 10%.

Severe BA is associated not only with frequent hospitalizations and increased mortality but also with high treatment costs.

As to it, there is a hot button issue of developing new drugs for treating patients not to be achieved effectively with standard therapy. Considering the leading pathogenesis role of IgE-mediated allergy, the use of drugs to block IgE makes it possible to control the disease at the earliest allergic reaction phase of the development. It was shown that the IgE elimination from the mast cells and basophils surface reduced the severity of acute allergic reactions, reduced the allergen-induced late phase of the immune response and infiltration with inflammatory cells. These anti-IgE antibodies effects have been shown in various studies.

One of these drugs is оmalizumab (Xolair®). The drug has been approved in various countries across the world, including the United States and the European Union for the severe allergic BA and chronic idiopathic urticaria treatment. In the Russian Federation, omalizumab was registered in May 2007.

The drug GNR-044 (JSC "GENERIUM", Russian Federation) is biosimilar to the original drug Xolair®. This study is aimed to compare the safety and pharmacokinetics of the drug GNR-044 (JSC "GENERIUM", Russian Federation) and the drug Xolair® in order to register of the drug GNR-044 (JSC "GENERIUM", Russian Federation), a lyophilizate for subcutaneous administration, in the Russian Federation.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • Federal State Budgetary Institution "State Scientific Center Institute of Immunology" by Federal Medical and Biological Agency of the Russian Federation
  • RF
    • Moscow, RF, Russian Federation, 117556
      • State budgetary institution of health care of the city of Moscow "City outpatients clinic No. 2 of the Department of Health of the city of Moscow"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women between the ages of 18 and 50 (inclusive) at the time of the Informed Consent Form.
2. The diagnosis is "healthy" according to haematology and biochemical blood tests, urinalysis, results of physical examination, measurements of vital signs, results of electrocardiography.
3. Bodyweight from 40 to 90 kg inclusive.
4. Body mass index 18.5-30 kg / m2 inclusive.
5. Initial concentration of total IgE: ≥30 IU / ml and ≤300 IU / ml.
6. Comply with the rules of contraception by the study participants.

Exclusion Criteria:

1. Monoclonal antibodies administration within 1 year before taking omalizumab.
2. Hypersensitivity to any of the used study drug, to their components, history of an undesirable drug reaction.
3. Concurrent diseases and conditions with potential impact on the patient's safety, pharmacokinetics or pharmacodynamics.
4. The drug's use that affects pharmacokinetics or pharmacodynamics (injectable glucocorticosteroid drugs, allergen-specific immunotherapy, immunosuppressive drugs, vaccination within 30 days before signing informed consent and/or the need for vaccination during the study period).
5. Women of childbearing potential not using the contraception method(s), as well as women who are breastfeeding.
6. Patients with severe medical conditions that in the view of the investigator prohibits participation in the study.
7. Concurrent therapy with investigational agents.
8. A history of autoimmune disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GNR-044 (JSC "GENERIUM", the Russian Federation); 150 mg of omalizumab was subcutaneously injected once in the deltoid muscle area	Biological: Omalizumab (JSC "GENERIUM", the Russian Federation); 150 mg of omalizumab was subcutaneously injected once in the deltoid muscle area; Other Names: omalizumab; GNR-044
Active Comparator: Xolair® (Novartis Pharma AG, Switzerland); 150 mg of omalizumab was subcutaneously injected once in the deltoid muscle area	Biological: Xolair® (Novartis Pharma AG, Switzerland); 150 mg of omalizumab was subcutaneously injected once in the deltoid muscle area; Other Names: omalizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the pharmacokinetic parameter - Tmax	Tmax - Time to reach maximum concentration (day)	5-15 minutes before drug administration, in 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 984, 1344, 1680, 2016 hours after drug administration
Assessment of the pharmacokinetic parameters - Cmax	Cmax - Maximum concentration (μg / ml)	5-15 minutes before drug administration, in 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 984, 1344, 1680, 2016 hours after drug administration
Assessment of the pharmacokinetic parameters - AUC0-∞	AUC0-∞ - Area under the concentration-time curve (mgday / ml) in the time interval from 0 to ∞	5-15 minutes before drug administration, in 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 984, 1344, 1680, 2016 hours after drug administration
Assessment of the pharmacokinetic parameters - AUC0-2016 h	AUC0-2016 h - Area under the concentration-time curve (mg day / ml) in the time interval from 0 to 2016 h	5-15 minutes before drug administration, in 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 984, 1344, 1680, 2016 hours after drug administration
Assessment of the pharmacokinetic parameters - Kel	Kel - Elimination constant (day - 1)	5-15 minutes before drug administration, in 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 984, 1344, 1680, 2016 hours after drug administration
Assessment of the pharmacokinetic parameters - Vd/F	Vd/F - Apparent volume of distribution (l)	5-15 minutes before drug administration, in 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 984, 1344, 1680, 2016 hours after drug administration
Assessment of the pharmacokinetic parameters - CL/F	CL/F - Apparent systemic clearance (ml / day)	5-15 minutes before drug administration, in 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 984, 1344, 1680, 2016 hours after drug administration
Assessment of the pharmacokinetic parameters - T1/2	T1/2 - Half-life (day)	5-15 minutes before drug administration, in 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 984, 1344, 1680, 2016 hours after drug administration
Assessment of the pharmacodynamics parameters - AUEC	AUEC - (area under efficacy curve) the area under the curve "Relative difference in the free IgE concentration compared to the initial value - time"	5-15 minutes before drug administration, in 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 984, 1344, 1680, 2016 hours after drug administration
Assessment of the pharmacodynamics parameters - Cmax	Cmax - Maximum relative difference in free IgE concentration compared to baseline	5-15 minutes before drug administration, in 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 984, 1344, 1680, 2016 hours after drug administration
Assessment of the pharmacodynamics parameters - relative difference estimation in free IgE concentration at each measurement point compared to baseline	• relative difference estimation in free IgE concentration at each measurement point compared to baseline	5-15 minutes before drug administration, in 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 984, 1344, 1680, 2016 hours after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The frequency of antidrug antibodies formation	The frequency of antidrug antibodies formation	Before drug administration, on Day 15 ± 1 day, Day 42 ± 2 days and Day 85 ± 2 days after drug administration
Antidrug antibody rate	Antidrug antibody rate	Before drug administration, on Day 15 ± 1 day, Day 42 ± 2 days and Day 85 ± 2 days after drug administration
Neutralising antibodies rate	Neutralising antibodies rate	Before drug administration, on Day 15 ± 1 day, Day 42 ± 2 days and Day 85 ± 2 days after drug administration
Body temperature measurement	A medical examination by an investigator to determine the state of a person's health, identify risk factors for AE and SAE: - body temperature measurement	Before drug administration, on Day 1-7, 11, 15, 22, 29, 42, 57, 71, 85 after drug administration
Systolic blood pressure	A medical examination by an investigator to determine the state of a person's health, identify risk factors for AE and SAE: - systolic blood pressure	Before drug administration, on Day 1-7, 11, 15, 22, 29, 42, 57, 71, 85 after drug administration
Diastolic blood pressure	A medical examination by an investigator to determine the state of a person's health, identify risk factors for AE and SAE: - diastolic blood pressure	Before drug administration, on Day 1-7, 11, 15, 22, 29, 42, 57, 71, 85 after drug administration
Heart rate	A medical examination by an investigator to determine the state of a person's health, identify risk factors for AE and SAE: - heart rate	Before drug administration, on Day 1-7, 11, 15, 22, 29, 42, 57, 71, 85 after drug administration
Respiratory rate	A medical examination by an investigator to determine the state of a person's health, identify risk factors for AE and SAE: - respiratory rate	Before drug administration, on Day 1-7, 11, 15, 22, 29, 42, 57, 71, 85 after drug administration
Electrocardiogram (ECG) assessment of RR Interval	A medical examination by an investigator to determine the state of a person's health, identify risk factors for AE and SAE - ECG RR Interval	Before drug administration, on Day 29, 85 after drug administration
Electrocardiogram (ECG) assessment of PQ Interval	A medical examination by an investigator to determine the state of a person's health, identify risk factors for AE and SAE - ECG PQ Interval	Before drug administration, on Day 29, 85 after drug administration
Electrocardiogram (ECG) assessment of QRS Interval	A medical examination by an investigator to determine the state of a person's health, identify risk factors for AE and SAE - ECG QRS Interval	Before drug administration, on Day 29, 85 after drug administration
Electrocardiogram (ECG) assessment of QT Interval	A medical examination by an investigator to determine the state of a person's health, identify risk factors for AE and SAE - ECG QT Interval	Before drug administration, on Day 29, 85 after drug administration

Collaborators and Investigators

• Sponsor: AO GENERIUM
• Investigators: Study Chair: Oksana A Markova, MD, Head of the scientific department

Publications and helpful links

Helpful Links

• Clinical Trials Register
• Clinical Trials Register

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2017
• Primary Completion (Actual): September 6, 2017
• Study Completion (Actual): September 6, 2017

Study Registration Dates

• First Submitted: October 12, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 23, 2020

Study Record Updates

• Last Update Posted (Actual): October 23, 2020
• Last Update Submitted That Met QC Criteria: October 19, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: hypersensitivity; safety; pharmacokinetics; pharmacodynamics; omalizumab; biosimilar; health volunteers; immune system diseases; equivalence; bronchial asthma; urticaria; humanized monoclonal antibodies; total or free IgE; anti-allergic agents; anti-asthmatic agents; respiratory system agents
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Antibodies, Monoclonal; Omalizumab
• Other Study ID Numbers: OMA-HVL-I; №88 eff.data 16 Feb 2017 (Registry Identifier: Ministry of Health of Russia approval number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: NAP

Drug and device information, study documents

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