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

NCT04898309 | Withdrawn Phase 2 DMC

• 2 other identifiers: CIR-HAE-II-III#210, April 16, 2
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

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

Conditions

Hereditary Angioedema

Keywords

Hereditary angioedema; Swelling; GNR-038; C1-inhibitor; Mutation; SERPING1 gene; HAE; Genetic disease; C1-INH deficiency; Hypersensitivity; Immune System Diseases; Genetic Diseases, Inborn; Immunologic Factors; Physiological Effects of Drugs; Complement Inactivating Agents; Immunosuppressive Agents; Angioedema; Angioedemas, Hereditary; Complement C1 Inhibitor Protein; Complement C1 Inactivator Proteins

Outcome Measures

Primary Outcomes (1)

• Time to symptoms relief onset of acute HAE attack within 24 hours after the end of the drug administration.

  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

  24 hours

Secondary Outcomes (10)

• 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

• Time to minimum manifestation onset of acute HAE attack symptoms after the completion of study drug administration.

  24 hours

• 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

Study Arms (6)

Study stage 1: GNR-038, 50 МЕ/ kg

EXPERIMENTAL

Recombinant C1 esterase inhibitor

Drug: GNR-038, 50 МЕ/ kg

Study stage 1: GNR-038, 100 МЕ/ kg

EXPERIMENTAL

Recombinant C1 esterase inhibitor

Drug: GNR-038, 100 МЕ/ kg

Study stage 1: Berinert®, 20 МЕ/ kg

EXPERIMENTAL

Human C1 esterase inhibitor

Drug: Berinert®, 20 МЕ/ kg

Study stage 1: Placebo

EXPERIMENTAL

Placebo

Drug: Placebo

Study stage 2: GNR-038 in selected dose

EXPERIMENTAL

Recombinant C1 esterase inhibitor

Drug: GNR-038. The dose will be selected according to results of stage 1 clinical trial.

Study stage 2: Berinert®, 20 МЕ/ kg

EXPERIMENTAL

Human C1 esterase inhibitor

Drug: Berinert®, 20 МЕ/ kg

Interventions

GNR-038, 50 МЕ/ kg DRUG

A single intravenous infusion of GNR-038, 50 МЕ/ kg less than 5 hours after the onset of edema.

Also known as: Recombinant C1 esterase inhibitor, 50 МЕ/ kg

Study stage 1: GNR-038, 50 МЕ/ kg

GNR-038, 100 МЕ/ kg DRUG

A single intravenous infusion of GNR-038, 100 МЕ/ kg less than 5 hours after the onset of edema.

Also known as: Recombinant C1 esterase inhibitor, 100 МЕ/ kg

Study stage 1: GNR-038, 100 МЕ/ kg

Berinert®, 20 МЕ/ kg DRUG

A single intravenous infusion of Berinert®, 20 МЕ/ kg less than 5 hours after the onset of edema.

Also known as: Human C1 esterase inhibitor

Study stage 1: Berinert®, 20 МЕ/ kg

Placebo DRUG

A single intravenous infusion of Placebo less than 5 hours after the onset of edema.

Study stage 1: Placebo

GNR-038. The dose will be selected according to results of stage 1 clinical trial. DRUG

A single intravenous infusion of GNR-038 less than 5 hours after the onset of edema.

Also known as: Recombinant C1 esterase inhibitor.

Study stage 2: GNR-038 in selected dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women 18 years and older at the time of signing the Informed Consent Form.
• Availability of written informed consent signed by the patient prior to the start of any procedures related to the study.
• Confirmed diagnosis of HAE:
• C4 level \<50% of the lower limit of the range of normal laboratory values and one of the points below:
• the C1INH level \<50% of the lower limit of the range of normal laboratory values, OR
• the level of C1INH within normal values, while the level of functional activity of C1INH is below 50% of the lower limit of the range of normal values.
• Localization of the edema in the abdominal cavity, in the face area (lips, eyelids, subcutaneous tissue), limbs, trunk or in the area of the external genitals in the anamnesis.
• ≥4 HAE attacks requiring treatment or causing significant functional impairment for 2 consecutive months in the 3-month period prior to Screening, properly documented in the medical records.
• Patient's consent to adhere to reliable methods of contraception.

You may not qualify if:

• Deviation of the C1q level below the normal limit.
• The presence of anti-C1INH autoantibodies.
• Allergic reactions to the components of C1INH drugs or other blood components.
• Glomerular filtration rate ≤59 ml/min/1.73 m2, calculated by the formula CKD-EPI Creatinine Equation (2009) (see Appendix).
• The concentration of peripheral blood leukocytes \>20\*109/L.
• Participation in clinical trials of C1-esterase inhibitor drugs, blood transfusion and its components during the last 90 days prior to screening.
• Participation in clinical trials of any other investigational drugs within the last 30 (thirty) days prior to screening.
• Positive laboratory results for HIV and hepatitis B and C.
• Pregnancy and lactation.
• Diseases and conditions associated with thrombosis (myocardial infarction, transient ischemic attacks, deep and superficial vein thrombosis, and pulmonary embolism) less than 6 months before the start of the screening period, as well as an increased risk of arterial or venous thrombosis according to the study doctor's opinion.
• Concomitant diseases and conditions that according to the study doctor's opinion put the patient's safety at risk when participating in the study, or that will affect the analysis of safety data if this disease/condition worsens during the study, including:
• Mental illness;
• Diseases of the immune and endocrine system that are not controlled by drug therapy (including decompensated diabetes mellitus and thyroid diseases);
• Hematological diseases requiring chemotherapy;
• Cancer or cancer in the past medical history, with the exception of cured basal cell carcinoma;

Sponsors & Collaborators

• AO GENERIUM: lead

Study Sites (5)

National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia

Moscow, 115522, Russia

Location

Moscow City Clinical Hospital 52

Moscow, 123182, Russia

Location

Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology

Moscow, 630099, Russia

Location

Rostov State Medical University

Rostov-on-Don, 344022, Russia

Location

LLC "Scientific Medical Center of General Therapy and Pharmacology"

Stavropol, 355000, Russia

Location

Related Links

• Clinical trial registry, Ministry of Health of Russian Federation
• Clinical trial registry

MeSH Terms

Conditions

Angioedemas, Hereditary; Genetic Diseases, Inborn; Hypersensitivity; Immune System Diseases; Angioedema

Interventions

Complement C1 Inhibitor Protein

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Immunologic Deficiency Syndromes

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Complement C1 Inactivator Proteins; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Complement Inactivator Proteins; Complement System Proteins; Immunoproteins; Blood Proteins; Proteins

Study Officials

• Oksana A. Markova, MD

  AO GENERIUM

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: At the first stage - the study will be blinded, at the second stage - open-label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two-stage study. In the first stage - 4 groups are presented. At the second stage - 2 study groups 200 HAE attacks to be randomized in 50 patients

Study Record Dates

• First Submitted: May 18, 2021
• First Posted: May 24, 2021
• Study Start: December 1, 2021
• Primary Completion: May 31, 2023
• Study Completion: May 31, 2023
• Last Updated: February 4, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

RU (5)