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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: Omalizumab (JSC GENERIUM, the Russian Federation)
* Biological: Xolair® (Novartis Pharma AG, Switzerland)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women between the ages of 18 and 50 (inclusive) at the time of the Informed Consent Form. The diagnosis is healthy according to haematology and biochemical blood tests, urinalysis, results of physical examination, measurements of vital signs, results of electrocardiography. Bodyweight from 40 to 90 kg inclusive. Body mass index 18.5-30 kg / m2 inclusive. Initial concentration of total IgE: ≥30 IU / ml and ≤300 IU / ml. Comply with the rules of contraception by the study participants. Exclusion Criteria: Monoclonal antibodies administration within 1 year before taking omalizumab. Hypersensitivity to any of the used study drug, to their components, history of an undesirable drug reaction. Concurrent diseases and conditions with potential impact on the patient's safety, pharmacokinetics or pharmacodynamics. 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). Women of childbearing potential not using the contraception method(s), as well as women who are breastfeeding. Patients with severe medical conditions that in the view of the investigator prohibits participation in the study. Concurrent therapy with investigational agents. A history of autoimmune disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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omalizumab, humanized monoclonal antibodies, total or free IgE, pharmacokinetics, pharmacodynamics, safety, bronchial asthma, health volunteers, equivalence, biosimilar, anti-allergic agents, anti-asthmatic agents, respiratory system agents, hypersensitivity, immune system diseases, urticaria