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

NCT04601389 | Completed Phase 1

• 2 other identifiers: OMA-HVL-I№88 eff.data 16 Feb 2017
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 2

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

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

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (12)

• 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

  Before drug administration, on Day 15 ± 1 day, Day 42 ± 2 days and Day 85 ± 2 days after drug administration

• 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

  Before drug administration, on Day 1-7, 11, 15, 22, 29, 42, 57, 71, 85 after drug administration

• Systolic blood pressure

  Before drug administration, on Day 1-7, 11, 15, 22, 29, 42, 57, 71, 85 after drug administration

Study Arms (2)

GNR-044 (JSC "GENERIUM", the Russian Federation)

EXPERIMENTAL

150 mg of omalizumab was subcutaneously injected once in the deltoid muscle area

Biological: Omalizumab (JSC "GENERIUM", the Russian Federation)

Xolair® (Novartis Pharma AG, Switzerland)

ACTIVE COMPARATOR

150 mg of omalizumab was subcutaneously injected once in the deltoid muscle area

Biological: Xolair® (Novartis Pharma AG, Switzerland)

Interventions

Omalizumab (JSC "GENERIUM", the Russian Federation) BIOLOGICAL

150 mg of omalizumab was subcutaneously injected once in the deltoid muscle area

Also known as: omalizumab, GNR-044

GNR-044 (JSC "GENERIUM", the Russian Federation)

Xolair® (Novartis Pharma AG, Switzerland) BIOLOGICAL

150 mg of omalizumab was subcutaneously injected once in the deltoid muscle area

Also known as: omalizumab

Xolair® (Novartis Pharma AG, Switzerland)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AO GENERIUM: lead

Study Sites (2)

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, 117556, Russia

Location

Federal State Budgetary Institution "State Scientific Center Institute of Immunology" by Federal Medical and Biological Agency of the Russian Federation

Moscow, 115478, Russia

Location

Related Links

• Clinical Trials Register

MeSH Terms

Conditions

Asthma; Hypersensitivity; Immune System Diseases; Urticaria

Interventions

Omalizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Study Officials

• Oksana A Markova, MD

  Head of the scientific department

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Interventional

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: October 23, 2020
• Study Start: April 18, 2017
• Primary Completion: September 6, 2017
• Study Completion: September 6, 2017
• Last Updated: October 23, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

RU (2)