Safety and Pharmacokinetics of GNR-038 in Healthy Volunteers

Phase 1

Completed

• Conditions: Hereditary Angioedema
• Interventions: Biological: GNR-038, 50 МЕ/kg; Biological: GNR-038, 25 МЕ/kg; Biological: GNR-038, 100 МЕ/kg

• Registration Number: NCT04557319
• Lead Sponsor: AO GENERIUM

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.

Study Timeline

• Study Start: 2020-03-10
• Status Verified: 2020-08
• Study First Submitted: 2020-08-26
• Primary Completion: 2020-08-27
• Study Completion: 2020-08-27
• Study First Submitted QC: 2020-09-15
• Study First Posted: 2020-09-21
• Last Update Submitted: 2020-09-28
• Last Update Posted: 2020-09-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
GNR-038, 50 МЕ/kg	GNR-038, 50 МЕ/kg	Recombinant C1-esterase (50 ME/kg) inhibitor intravenous infusion
GNR-038, 25 МЕ/kg	GNR-038, 25 МЕ/kg	Recombinant C1-esterase (25 ME/kg) inhibitor intravenous infusion
GNR-038, 100 МЕ/kg	GNR-038, 100 МЕ/kg	Recombinant C1-esterase (100 ME/kg) inhibitor intravenous infusion

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	Pharmacokinetic parameters
Mean retention time (MRT)	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8	Pharmacokinetic parameters
Elimination rate constant (Kel)	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8	Pharmacokinetic parameters
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	Pharmacokinetic parameters
Half-life (T1/2)	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8	Pharmacokinetic parameters
Overall clearance (Cl)	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8	Pharmacokinetic parameters
Kinetic volume of distribution (Vz)	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8	Pharmacokinetic parameters

Trial Locations

Locations (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, Russian Federation