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Safety and Pharmacokinetics of GNR-038 in Healthy Volunteers

Primary Purpose

Hereditary Angioedema

Status

Completed

Phase

Phase 1

Locations

Russian Federation

Study Type

Interventional

Intervention

GNR-038, 25 МЕ/kg

GNR-038, 50 МЕ/kg

GNR-038, 100 МЕ/kg

About this trial

This is an interventional other trial for Hereditary Angioedema focused on measuring 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

Eligibility Criteria

18 Months - 50 Years (Child, Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria

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.

Exclusion Criteria

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;
Pregnancy or breastfeeding;
Other reasons that prevent the volunteer from study participating or create an unreasonable risk in the investigator opinion.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

GNR-038, 25 МЕ/kg

GNR-038, 50 МЕ/kg

GNR-038, 100 МЕ/kg

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Peak Plasma Concentration (Cmax)

Pharmacokinetic parameters

Area under the plasma concentration versus time curve (AUC)

Pharmacokinetic parameters

Half-life (T1/2)

Pharmacokinetic parameters

Elimination rate constant (Kel)

Pharmacokinetic parameters

Mean retention time (MRT)

Pharmacokinetic parameters

Overall clearance (Cl)

Pharmacokinetic parameters

Kinetic volume of distribution (Vz)

Pharmacokinetic parameters

Full Information

NCT ID

NCT04557319

First Posted

August 26, 2020

Last Updated

September 28, 2020

Sponsor

AO GENERIUM

1. Study Identification

Unique Protocol Identification Number

NCT04557319

Brief Title

Safety and Pharmacokinetics of GNR-038 in Healthy Volunteers

Official Title

An Open Study of the Safety and Pharmacokinetics of GNR-038 in Sequential Dose-increase Cohorts in Healthy Volunteers

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Completed

Study Start Date

March 10, 2020 (Actual)

Primary Completion Date

August 27, 2020 (Actual)

Study Completion Date

August 27, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AO GENERIUM

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

Detailed Description

Hereditary angioedema (HAE) is a rare potentially life-threatening genetically determined disease associated with a deficiency or impairment of C1 esterase inhibitor (C1 inhibitor) functional activity. Main clinical manifestations of HAE are recurrent mucous membranes edema and localization of the derma deep layers. Attack persist from several hours to several days and disappear without a trace in most cases, without additional therapy. The prevalence of the disease in the world is from 1:10 000 to 1: 150 000. The plasma/recombinant C1 inhibitor use to compensate for its deficiency or insufficient functional activity in patients with HAE is recommended both for severe and for long-term and short-term (before surgical interventions and dental manipulations) prophylaxis. GNR-038 is a recombinant C1 inhibitor (rhC1-inh), which is a complete structural and functional analogue of the plasma C1 inhibitor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

Sequential dose-increase cohorts in healthy volunteers

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

36 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GNR-038, 25 МЕ/kg

Arm Type

Experimental

Arm Description

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

Arm Title

GNR-038, 50 МЕ/kg

Arm Type

Experimental

Arm Description

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

Arm Title

GNR-038, 100 МЕ/kg

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

GNR-038, 25 МЕ/kg

Other Intervention Name(s)

rC1inh, 25 МЕ/kg

Intervention Description

25 МЕ/kg once per study

Intervention Type

Biological

Intervention Name(s)

GNR-038, 50 МЕ/kg

Other Intervention Name(s)

rC1inh, 50 МЕ/kg

Intervention Description

50 МЕ/kg once per study

Intervention Type

Biological

Intervention Name(s)

GNR-038, 100 МЕ/kg

Other Intervention Name(s)

rC1inh, 100 МЕ/kg

Intervention Description

100 МЕ/kg once per study

Primary Outcome Measure Information:

Title

Number of participants with Adverse Events

Description

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

Time Frame

28 Days

Secondary Outcome Measure Information:

Title

Peak Plasma Concentration (Cmax)

Description

Pharmacokinetic parameters

Time Frame

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

Title

Area under the plasma concentration versus time curve (AUC)

Description

Pharmacokinetic parameters

Time Frame