Safety and Pharmacokinetics of GNR-038 in Healthy Volunteers

Hereditary Angioedema Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04557319
• Other study ID #: CIR-HAET-I
• Secondary ID: #725 eff date 20
• Status: Completed
• Phase: Phase 1
• Start date: March 10, 2020
• Est. completion date: August 27, 2020

Study information

• Verified date: August 2020
• Source: AO GENERIUM
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: August 27, 2020
• Est. primary completion date: August 27, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Months to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

Biological:
• GNR-038, 25 ??/kg
25 ??/kg once per study
• GNR-038, 50 ??/kg
50 ??/kg once per study
• GNR-038, 100 ??/kg
100 ??/kg once per study

Locations

Country	Name	City	State
Russian Federation	State budgetary institution of healthcare of the city of Moscow "?ity polyclinic No. 2 of the Department of healthcare of the city of Moscow"	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
AO GENERIUM

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Peak Plasma Concentration (Cmax)	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
Secondary	Area under the plasma concentration versus time curve (AUC)	Pharmacokinetic parameters	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Secondary	Half-life (T1/2)	Pharmacokinetic parameters	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Secondary	Elimination rate constant (Kel)	Pharmacokinetic parameters	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Secondary	Mean retention time (MRT)	Pharmacokinetic parameters	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Secondary	Overall clearance (Cl)	Pharmacokinetic parameters	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Secondary	Kinetic volume of distribution (Vz)	Pharmacokinetic parameters	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8