- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04898309
Efficacy and Safety of GNR-038 vs Berinert® in Patients With Hereditary Angioedema
January 21, 2022 updated by: AO GENERIUM
A Placebo-controlled Randomized Trial to Evaluate the Efficacy and Safety of GNR-038 in Comparison With Berinert® for Acute Attacks Relief in Patients With Hereditary Angioedema
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
Study Overview
Status
Withdrawn
Conditions
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 Type
Interventional
Phase
- Phase 2
- Phase 3
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
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Moscow, Russian Federation, 115522
- National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia
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Moscow, Russian Federation, 123182
- Moscow City Clinical Hospital 52
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Moscow, Russian Federation, 630099
- Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology
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Rostov-on-Don, Russian Federation, 344022
- Rostov State Medical University
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Stavropol', Russian Federation, 355000
- LLC "Scientific Medical Center of General Therapy and Pharmacology"
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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
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria
- 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.
Exclusion Criteria
- Deviation of the C1q level below the normal limit.
- B-cell lymphoproliferative diseases in the anamnesis or at the time of inclusion in clinical trial.
- 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.
- Drug addiction, solvent abuse, alcoholism in the anamnesis or at the time of inclusion.
- 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;
- Decompensated liver diseases.
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: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Study stage 1: GNR-038, 50 МЕ/ kg
Recombinant C1 esterase inhibitor
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A single intravenous infusion of GNR-038, 50 МЕ/ kg less than 5 hours after the onset of edema.
Other Names:
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Experimental: Study stage 1: GNR-038, 100 МЕ/ kg
Recombinant C1 esterase inhibitor
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A single intravenous infusion of GNR-038, 100 МЕ/ kg less than 5 hours after the onset of edema.
Other Names:
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Experimental: Study stage 1: Berinert®, 20 МЕ/ kg
Human C1 esterase inhibitor
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A single intravenous infusion of Berinert®, 20 МЕ/ kg less than 5 hours after the onset of edema.
Other Names:
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Experimental: Study stage 1: Placebo
Placebo
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A single intravenous infusion of Placebo less than 5 hours after the onset of edema.
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Experimental: Study stage 2: GNR-038 in selected dose
Recombinant C1 esterase inhibitor
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A single intravenous infusion of GNR-038 less than 5 hours after the onset of edema.
Other Names:
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Experimental: Study stage 2: Berinert®, 20 МЕ/ kg
Human C1 esterase inhibitor
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A single intravenous infusion of Berinert®, 20 МЕ/ kg less than 5 hours after the onset of edema.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to symptoms relief onset of acute HAE attack within 24 hours after the end of the drug administration.
Time Frame: 24 hours
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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
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24 hours
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to complete resolution of the symptoms of an acute HAE attack within 24 hours after the end of the study drug administration.
Time Frame: 24 hours
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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
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24 hours
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Time to minimum manifestation onset of acute HAE attack symptoms after the completion of study drug administration.
Time Frame: 24 hours
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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
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24 hours
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The proportion of HAE exacerbation episodes that achieved symptom relief after 1 hour and 4 (four) hours after the end of study drug administration.
Time Frame: 1 hour; 4 hours.
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1 hour; 4 hours.
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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.
Time Frame: 24 hours
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24 hours
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The rate of attacks that required additional administration of emergency drugs (human C1-esterase inhibitor or icatibant).
Time Frame: 24 hours
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24 hours
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The rate of attacks that did not respond therapeutically to the study drug administration
Time Frame: 4 hours; 24 hours
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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.
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4 hours; 24 hours
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The intensity of acute HAE attack symptoms within 24 (twenty-four) hours after study drug administration.
Time Frame: 24 hours
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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
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24 hours
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Frequency of adverse events.
Time Frame: 14 days
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14 days
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Frequency of anti-drug antibody formation.
Time Frame: 7 and 14 days
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7 and 14 days
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The level of anti-drug antibodies neutralizing activity.
Time Frame: 7 and 14 days
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Laboratory measurement of antidrug antibody with neutralixing activity.
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7 and 14 days
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
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 (Anticipated)
December 1, 2021
Primary Completion (Anticipated)
May 31, 2023
Study Completion (Anticipated)
May 31, 2023
Study Registration Dates
First Submitted
May 18, 2021
First Submitted That Met QC Criteria
May 21, 2021
First Posted (Actual)
May 24, 2021
Study Record Updates
Last Update Posted (Actual)
February 4, 2022
Last Update Submitted That Met QC Criteria
January 21, 2022
Last Verified
January 1, 2022
More Information
Terms related to this study
Keywords
- Hypersensitivity
- Immune System Diseases
- Genetic Diseases, Inborn
- Mutation
- HAE
- Physiological Effects of Drugs
- Genetic disease
- Immunologic Factors
- Angioedema
- Hereditary angioedema
- Immunosuppressive Agents
- Swelling
- GNR-038
- C1-inhibitor
- SERPING1 gene
- C1-INH deficiency
- Complement Inactivating Agents
- Angioedemas, Hereditary
- Complement C1 Inhibitor Protein
- Complement C1 Inactivator Proteins
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Skin Diseases
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Hypersensitivity, Immediate
- Genetic Diseases, Inborn
- Skin Diseases, Vascular
- Hypersensitivity
- Urticaria
- Hereditary Complement Deficiency Diseases
- Primary Immunodeficiency Diseases
- Angioedema
- Angioedemas, Hereditary
- Physiological Effects of Drugs
- Immunosuppressive Agents
- Immunologic Factors
- Complement Inactivating Agents
- Complement C1 Inhibitor Protein
- Complement C1 Inactivator Proteins
- Complement C1s
Other Study ID Numbers
- CIR-HAE-II-III
- #210, April 16, 2 (Other Identifier: Ministry of Health of Russian Federation)
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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