Clinical trial NCT04601389: Study of Pharmacokinetics, Pharmacodynamics and Safety Assessment of GNR-044 (JSC GENERIUM, Russia) and Xolair®
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: 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
Lead sponsor: AO GENERIUM
Sponsor class: INDUSTRY
First posted: 2020-10-23
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Interventional
Primary purpose: OTHER

Brief 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of the pharmacokinetic parameter - Tmax
timeFrame: 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
measure: Assessment of the pharmacokinetic parameters - Cmax
timeFrame: 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
measure: Assessment of the pharmacokinetic parameters - AUC0-∞
timeFrame: 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
measure: Assessment of the pharmacokinetic parameters - AUC0-2016 h
timeFrame: 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
measure: Assessment of the pharmacokinetic parameters - Kel
timeFrame: 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
measure: Assessment of the pharmacokinetic parameters - Vd/F
timeFrame: 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
measure: Assessment of the pharmacokinetic parameters - CL/F
timeFrame: 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
measure: Assessment of the pharmacokinetic parameters - T1/2
timeFrame: 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
measure: Assessment of the pharmacodynamics parameters - AUEC
timeFrame: 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
measure: Assessment of the pharmacodynamics parameters - Cmax
timeFrame: 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
measure: Assessment of the pharmacodynamics parameters - relative difference estimation in free IgE concentration at each measurement point compared to baseline
timeFrame: 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 outcomes:
measure: The frequency of antidrug antibodies formation
timeFrame: Before drug administration, on Day 15 ± 1 day, Day 42 ± 2 days and Day 85 ± 2 days after drug administration
measure: Antidrug antibody rate
timeFrame: Before drug administration, on Day 15 ± 1 day, Day 42 ± 2 days and Day 85 ± 2 days after drug administration
measure: Neutralising antibodies rate
timeFrame: Before drug administration, on Day 15 ± 1 day, Day 42 ± 2 days and Day 85 ± 2 days after drug administration
measure: Body temperature measurement
timeFrame: Before drug administration, on Day 1-7, 11, 15, 22, 29, 42, 57, 71, 85 after drug administration
measure: Systolic blood pressure
timeFrame: Before drug administration, on Day 1-7, 11, 15, 22, 29, 42, 57, 71, 85 after drug administration
measure: Diastolic blood pressure
timeFrame: Before drug administration, on Day 1-7, 11, 15, 22, 29, 42, 57, 71, 85 after drug administration
measure: Heart rate
timeFrame: Before drug administration, on Day 1-7, 11, 15, 22, 29, 42, 57, 71, 85 after drug administration
measure: Respiratory rate
timeFrame: Before drug administration, on Day 1-7, 11, 15, 22, 29, 42, 57, 71, 85 after drug administration
measure: Electrocardiogram (ECG) assessment of RR Interval
timeFrame: Before drug administration, on Day 29, 85 after drug administration
measure: Electrocardiogram (ECG) assessment of PQ Interval
timeFrame: Before drug administration, on Day 29, 85 after drug administration
measure: Electrocardiogram (ECG) assessment of QRS Interval
timeFrame: Before drug administration, on Day 29, 85 after drug administration
measure: Electrocardiogram (ECG) assessment of QT Interval
timeFrame: Before drug administration, on Day 29, 85 after drug administration
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: 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"
state: RF
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution "State Scientific Center Institute of Immunology" by Federal Medical and Biological Agency of the Russian Federation
Study officials:
affiliation: Head of the scientific department
name: Oksana A Markova, MD
role: STUDY_CHAIR
References: