Safety and Pharmacokinetics of GNR-038 in Healthy Volunteers

September 28, 2020 updated by: AO GENERIUM

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Russian Federation
      • Moscow, Russian Federation, 117556
        • State budgetary institution of healthcare of the city of Moscow "Сity polyclinic No. 2 of the Department of healthcare of the city of Moscow"

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  1. Men and women aged 18 to 50 (inclusive) at the time of signing the Informed Consent Form.
  2. Body mass index (BMI) in the range from 18.5 to 30 kg / m2, body weight from 50 to 90 kg.
  3. 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.
  4. Availability of written informed consent obtained from the volunteer prior to any research-related procedures performance.
  5. Consent to follow the adequate contraceptive methods.

Exclusion Criteria

  1. Known hypersensitivity to the components of the study drug;
  2. Burdened allergic history;
  3. Standard laboratory and instrumental parameters values are outside the normal range;
  4. Cardiovascular, bronchopulmonary, neuroendocrine systems chronic diseases, as well as gastrointestinal tract, liver, kidneys, hematopoietic, immune systems diseases, mental illness;
  5. 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.
  6. Infection with human immunodeficiency virus (HIV), hepatitis B and C;
  7. Acute infectious diseases less than 4 weeks prior to the Screening Visit;
  8. Regular medication intake less than 2 weeks prior to the Screening Visit;
  9. For women - the hormonal contraceptives use or hormone replacement therapy for 3 months before the screening period start;
  10. 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;
  11. Blood donation (450 ml of blood or plasma and more) less than 3 months before the Screening Visit;
  12. Participation in clinical trials less than 3 months before the Screening Visit;
  13. 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;
  14. Drug addiction, substance abuse, positive urine test for the content of potent and narcotic drugs;
  15. Smoking more than 10 cigarettes a day;
  16. Pregnancy or breastfeeding;
  17. Other reasons that prevent the volunteer from study participating or create an unreasonable risk in the investigator opinion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GNR-038, 25 МЕ/kg
Recombinant C1-esterase (25 ME/kg) inhibitor intravenous infusion
Biological: GNR-038, 25 МЕ/kg
25 МЕ/kg once per study
Other Names:
  • rC1inh, 25 МЕ/kg
Experimental: GNR-038, 50 МЕ/kg
Recombinant C1-esterase (50 ME/kg) inhibitor intravenous infusion
Biological: GNR-038, 50 МЕ/kg
50 МЕ/kg once per study
Other Names:
  • rC1inh, 50 МЕ/kg
Experimental: GNR-038, 100 МЕ/kg
Recombinant C1-esterase (100 ME/kg) inhibitor intravenous infusion
Biological: GNR-038, 100 МЕ/kg
100 МЕ/kg once per study
Other Names:
  • rC1inh, 100 МЕ/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with Adverse Events
Time Frame: 28 Days
Adverse events, Laboratory tests, Vital signs, Physical examination, 12-lead electrocardiogram, Allergic associated reaction, Infusion associated reaction, Antidrug antibody.
28 Days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak Plasma Concentration (Cmax)
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
Pharmacokinetic parameters
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)
Time Frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Pharmacokinetic parameters
Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Half-life (T1/2)
Time Frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Pharmacokinetic parameters
Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Elimination rate constant (Kel)
Time Frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Pharmacokinetic parameters
Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Mean retention time (MRT)
Time Frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Pharmacokinetic parameters
Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Overall clearance (Cl)
Time Frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Pharmacokinetic parameters
Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Kinetic volume of distribution (Vz)
Time Frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Pharmacokinetic parameters
Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AO GENERIUM

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 10, 2020

Primary Completion (Actual)

August 27, 2020

Study Completion (Actual)

August 27, 2020

Study Registration Dates

First Submitted

August 26, 2020

First Submitted That Met QC Criteria

September 15, 2020

First Posted (Actual)

September 21, 2020

Study Record Updates

Last Update Posted (Actual)

September 30, 2020

Last Update Submitted That Met QC Criteria

September 28, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CIR-HAET-I
  • #725 eff date 20.12.2019 (Other Identifier: Clinical trial approval number, Ministry of Health of Russia)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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