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

Healthy Volunteers Clinical Trial

— NAP  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04601389
• Other study ID #: OMA-HVL-I
• Secondary ID: ?88 eff.data 16
• Status: Completed
• Phase: Phase 1
• Start date: April 18, 2017
• Est. completion date: September 6, 2017

Study information

• Verified date: October 2020
• Source: AO GENERIUM
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: September 6, 2017
• Est. primary completion date: September 6, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Biological:
• Omalizumab (JSC "GENERIUM", the Russian Federation)
150 mg of omalizumab was subcutaneously injected once in the deltoid muscle area
• Xolair® (Novartis Pharma AG, Switzerland)
150 mg of omalizumab was subcutaneously injected once in the deltoid muscle area

Locations

Country	Name	City	State
Russian Federation	Federal State Budgetary Institution "State Scientific Center Institute of Immunology" by Federal Medical and Biological Agency of the Russian Federation	Moscow
Russian Federation	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"	Moscow	RF

Sponsors (1)

Lead Sponsor	Collaborator
AO GENERIUM

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Assessment of the pharmacokinetic parameters - AUC0-8	AUC0-8 - Area under the concentration-time curve (mgday / ml) in the time interval from 0 to 8	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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