Safety and Pharmacokinetics of GNR-038 in Healthy Volunteers

NCT04557319 | Completed Phase 1 DMC

• 2 other identifiers: CIR-HAET-I#725 eff date 20.12.2019
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

It is an open-label dose-escalating study in sequential cohorts to assess safety and pharmacokinetics of GNR-038.

Conditions

Hereditary Angioedema

Keywords

Angioedema; Angioedemas, Hereditary; Vascular Diseases; Cardiovascular Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Genetic Diseases, Inborn; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs

Outcome Measures

Primary Outcomes (1)

• Number of participants with Adverse Events

  Adverse events, Laboratory tests, Vital signs, Physical examination, 12-lead electrocardiogram, Allergic associated reaction, Infusion associated reaction, Antidrug antibody.

  28 Days

Secondary Outcomes (7)

• Peak Plasma Concentration (Cmax)

  45, 30 and 15 minutes before GNR-038 infusion; 0, 15, 30 minutes, 1, 2, 4, 8,12,16, 24, 48, 72, 96, 120,144 and 168 hours after GNR-038 infusion

• Area under the plasma concentration versus time curve (AUC)

  Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8

• Half-life (T1/2)

  Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8

• Elimination rate constant (Kel)

  Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8

• Mean retention time (MRT)

  Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8

Study Arms (3)

GNR-038, 25 МЕ/kg

EXPERIMENTAL

Recombinant C1-esterase (25 ME/kg) inhibitor intravenous infusion

Biological: GNR-038, 25 МЕ/kg

GNR-038, 50 МЕ/kg

EXPERIMENTAL

Recombinant C1-esterase (50 ME/kg) inhibitor intravenous infusion

Biological: GNR-038, 50 МЕ/kg

GNR-038, 100 МЕ/kg

EXPERIMENTAL

Recombinant C1-esterase (100 ME/kg) inhibitor intravenous infusion

Biological: GNR-038, 100 МЕ/kg

Interventions

GNR-038, 25 МЕ/kg BIOLOGICAL

25 МЕ/kg once per study

Also known as: rC1inh, 25 МЕ/kg

GNR-038, 25 МЕ/kg

GNR-038, 50 МЕ/kg BIOLOGICAL

50 МЕ/kg once per study

Also known as: rC1inh, 50 МЕ/kg

GNR-038, 50 МЕ/kg

GNR-038, 100 МЕ/kg BIOLOGICAL

100 МЕ/kg once per study

Also known as: rC1inh, 100 МЕ/kg

GNR-038, 100 МЕ/kg

Eligibility Criteria

• Age: 18 Months - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Men and women aged 18 to 50 (inclusive) at the time of signing the Informed Consent Form.
• Body mass index (BMI) in the range from 18.5 to 30 kg / m2, body weight from 50 to 90 kg.
• The diagnosis is "healthy" according to the data of clinical and biochemical blood tests, urinalysis, results of physical examination, measurement of vital signs, results of electrocardiography.
• Availability of written informed consent obtained from the volunteer prior to any research-related procedures performance.
• Consent to follow the adequate contraceptive methods.

You may not qualify if:

• Known hypersensitivity to the components of the study drug;
• Burdened allergic history;
• Standard laboratory and instrumental parameters values are outside the normal range;
• Cardiovascular, bronchopulmonary, neuroendocrine systems chronic diseases, as well as gastrointestinal tract, liver, kidneys, hematopoietic, immune systems diseases, mental illness;
• Diseases and conditions associated with thrombosis (myocardial infarction, transient ischemic attacks, deep and superficial vein thrombosis, pulmonary embolism) less than 6 months before the screening period start, as well as an increased risk of arterial or venous thrombosis according to the investigator opinion.
• Infection with human immunodeficiency virus (HIV), hepatitis B and C;
• Acute infectious diseases less than 4 weeks prior to the Screening Visit;
• Regular medication intake less than 2 weeks prior to the Screening Visit;
• For women - the hormonal contraceptives use or hormone replacement therapy for 3 months before the screening period start;
• Systolic pressure less than 100 mmHg or above 140 mmHg; diastolic pressure less than 70 mmHg or above 90 mmHg; pulse rate less than 60 beats/min or more than 90 beats/min;
• Blood donation (450 ml of blood or plasma and more) less than 3 months before the Screening Visit;
• Participation in clinical trials less than 3 months before the Screening Visit;
• More than 10 alcohol units intake per week (1 unit of alcohol is equivalent to 1/2 liter of beer, 200 ml of wine or 50 ml of ethanol) OR anamnestic information about alcoholism, detection of ethanol in exhaled air;
• Drug addiction, substance abuse, positive urine test for the content of potent and narcotic drugs;
• Smoking more than 10 cigarettes a day;

Sponsors & Collaborators

• AO GENERIUM: lead

Study Sites (1)

State budgetary institution of healthcare of the city of Moscow "Сity polyclinic No. 2 of the Department of healthcare of the city of Moscow"

Moscow, 117556, Russia

Location

MeSH Terms

Conditions

Angioedemas, Hereditary; Angioedema; Vascular Diseases; Cardiovascular Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Immunologic Deficiency Syndromes

Study Officials

• Oksana A. Markova, MD

  AO GENERIUM

  STUDY CHAIR

Study Design

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

Model Details: Sequential dose-increase cohorts in healthy volunteers

Study Record Dates

• First Submitted: August 26, 2020
• First Posted: September 21, 2020
• Study Start: March 10, 2020
• Primary Completion: August 27, 2020
• Study Completion: August 27, 2020
• Last Updated: September 30, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)