Efficacy and Safety of GNR-038 vs Berinert® in Patients With Hereditary Angioedema

Phase 2

Withdrawn

• Conditions: Hereditary Angioedema
• Interventions: Drug: GNR-038, 50 МЕ/ kg; Drug: GNR-038. The dose will be selected according to results of stage 1 clinical trial.; Drug: Placebo; Drug: Berinert®, 20 МЕ/ kg; Drug: GNR-038, 100 МЕ/ kg

• Registration Number: NCT04898309
• Lead Sponsor: AO GENERIUM

Brief Summary

It is a placebo-controlled randomized trial to evaluate the efficacy and safety of GNR-038 in comparison with Berinert® in patients with hereditary angioedema

Detailed Description

Hereditary angioedema is a rare, potentially life-threatening genetically determined disease associated with a deficiency or impairment of the functional activity of the C1-esterase inhibitor (C1-inhibitor). The main clinical manifestation of hereditary angioedema is recurrent subcutaneous or submucosal swelling of various localization. Most often, the development of the disease is based on a mutation in the SERPING1 gene. The prevalence of the disease in the world ranges from 1:10 000 to 1:150 000. GNR-038 is a recombinant C1 inhibitor (rhC1INH), which is a complete structural and functional analog of the plasma C1 inhibitor. Phase I study results showed convincing safety and tolerability evidence of GNR-038.

Study Timeline

• Study First Submitted: 2021-05-18
• Study First Submitted QC: 2021-05-21
• Study First Posted: 2021-05-24
• Study Start: 2021-12-01
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-21
• Last Update Posted: 2022-02-04
• Primary Completion: 2023-05-31
• Study Completion: 2023-05-31

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study stage 1: GNR-038, 50 МЕ/ kg	GNR-038, 50 МЕ/ kg	Recombinant C1 esterase inhibitor
Study stage 2: GNR-038 in selected dose	GNR-038. The dose will be selected according to results of stage 1 clinical trial.	Recombinant C1 esterase inhibitor
Study stage 1: Placebo	Placebo	Placebo
Study stage 2: Berinert®, 20 МЕ/ kg	Berinert®, 20 МЕ/ kg	Human C1 esterase inhibitor
Study stage 1: GNR-038, 100 МЕ/ kg	GNR-038, 100 МЕ/ kg	Recombinant C1 esterase inhibitor
Study stage 1: Berinert®, 20 МЕ/ kg	Berinert®, 20 МЕ/ kg	Human C1 esterase inhibitor

Primary Outcome Measures

Name	Time	Method
Time to symptoms relief onset of acute HAE attack within 24 hours after the end of the drug administration.	24 hours	A persistent decrease in the intensity of symptoms by 20 mm from the initial level on the visual analogue scale (VAS) will be regarded as a relief of symptoms of HAE. 0 mm is the absence of symptoms, 100 mm is the maximum possible intensity of symptoms

Secondary Outcome Measures

Name	Time	Method
Frequency of adverse events.	14 days
Time to complete resolution of the symptoms of an acute HAE attack within 24 hours after the end of the study drug administration.	24 hours	Persistent absence of symptoms - 0 (zero) mm on the visual analogue scale (VAS). 0 mm is the absence of symptoms, 100 mm is the maximum possible intensity of symptoms
Time to minimum manifestation onset of acute HAE attack symptoms after the completion of study drug administration.	24 hours	Persistent reduction in the intensity of symptoms below 20 (twenty) mm on the visual analogue scale(VAS). 0 mm is the absence of symptoms, 100 mm is the maximum possible intensity of symptoms
The proportion of HAE exacerbation episodes that achieved symptom relief after 1 hour and 4 (four) hours after the end of study drug administration.	1 hour; 4 hours.
The rate of attacks with HAE current localization relapse or with the occurrence of a new acute attack of a different localization within 24 (twenty-four) hours after the study drug administration.	24 hours
The rate of attacks that required additional administration of emergency drugs (human C1-esterase inhibitor or icatibant).	24 hours
The rate of attacks that did not respond therapeutically to the study drug administration	4 hours; 24 hours	the lack of relief of HAE symptoms within 4 (four) hours after administration of the drug, the occurrence of a relapse of HAE of the current localization or the occurrence of a new acute attack of another localization within 24 (twenty-four) hours after drug administration, the need to use drugs that can weaken the symptoms of HAE (see drugs that are not recommended to treatment), within 24 (twenty-four) hours after drug administration.
The intensity of acute HAE attack symptoms within 24 (twenty-four) hours after study drug administration.	24 hours	HAE intensity wiil be measured by visual analogue scale (VAS). 0 mm is the absence of symptoms, 100 mm is the maximum possible intensity of symptoms
The level of anti-drug antibodies neutralizing activity.	7 and 14 days	Laboratory measurement of antidrug antibody with neutralixing activity.
Frequency of anti-drug antibody formation.	7 and 14 days

Trial Locations

Locations (5)

Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology; 🇷🇺 Moscow, Russian Federation

Moscow City Clinical Hospital 52; 🇷🇺 Moscow, Russian Federation

National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia; 🇷🇺 Moscow, Russian Federation

Rostov State Medical University; 🇷🇺 Rostov-on-Don, Russian Federation

LLC "Scientific Medical Center of General Therapy and Pharmacology"; 🇷🇺 Stavropol', Russian Federation