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

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Russian Federation
      • Moscow, Russian Federation, 115522
        • National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia
      • Moscow, Russian Federation, 123182
        • Moscow City Clinical Hospital 52
      • Moscow, Russian Federation, 630099
        • Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology
      • Rostov-on-Don, Russian Federation, 344022
        • Rostov State Medical University
      • Stavropol', Russian Federation, 355000
        • LLC "Scientific Medical Center of General Therapy and Pharmacology"

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  1. Men and women 18 years and older at the time of signing the Informed Consent Form.
  2. Availability of written informed consent signed by the patient prior to the start of any procedures related to the study.

  3. 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.
  4. 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.
  5. ≥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.
  6. Patient's consent to adhere to reliable methods of contraception.

Exclusion Criteria

  1. Deviation of the C1q level below the normal limit.
  2. B-cell lymphoproliferative diseases in the anamnesis or at the time of inclusion in clinical trial.
  3. The presence of anti-C1INH autoantibodies.
  4. Allergic reactions to the components of C1INH drugs or other blood components.
  5. Glomerular filtration rate ≤59 ml/min/1.73 m2, calculated by the formula CKD-EPI Creatinine Equation (2009) (see Appendix).
  6. The concentration of peripheral blood leukocytes >20*109/L.
  7. Drug addiction, solvent abuse, alcoholism in the anamnesis or at the time of inclusion.
  8. Participation in clinical trials of C1-esterase inhibitor drugs, blood transfusion and its components during the last 90 days prior to screening.
  9. Participation in clinical trials of any other investigational drugs within the last 30 (thirty) days prior to screening.
  10. Positive laboratory results for HIV and hepatitis B and C.
  11. Pregnancy and lactation.
  12. 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.

  13. 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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Study stage 1: GNR-038, 50 МЕ/ kg
Recombinant C1 esterase inhibitor
Drug: GNR-038, 50 МЕ/ kg
A single intravenous infusion of GNR-038, 50 МЕ/ kg less than 5 hours after the onset of edema.
Other Names:
  • Recombinant C1 esterase inhibitor, 50 МЕ/ kg
Experimental: Study stage 1: GNR-038, 100 МЕ/ kg
Recombinant C1 esterase inhibitor
Drug: GNR-038, 100 МЕ/ kg
A single intravenous infusion of GNR-038, 100 МЕ/ kg less than 5 hours after the onset of edema.
Other Names:
  • Recombinant C1 esterase inhibitor, 100 МЕ/ kg
Experimental: Study stage 1: Berinert®, 20 МЕ/ kg
Human C1 esterase inhibitor
Drug: Berinert®, 20 МЕ/ kg
A single intravenous infusion of Berinert®, 20 МЕ/ kg less than 5 hours after the onset of edema.
Other Names:
  • Human C1 esterase inhibitor
Experimental: Study stage 1: Placebo
Placebo
Drug: Placebo
A single intravenous infusion of Placebo less than 5 hours after the onset of edema.
Experimental: Study stage 2: GNR-038 in selected dose
Recombinant C1 esterase inhibitor
Drug: GNR-038. The dose will be selected according to results of stage 1 clinical trial.
A single intravenous infusion of GNR-038 less than 5 hours after the onset of edema.
Other Names:
  • Recombinant C1 esterase inhibitor.
Experimental: Study stage 2: Berinert®, 20 МЕ/ kg
Human C1 esterase inhibitor
Drug: Berinert®, 20 МЕ/ kg
A single intravenous infusion of Berinert®, 20 МЕ/ kg less than 5 hours after the onset of edema.
Other Names:
  • Human C1 esterase inhibitor

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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
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
24 hours
Time to minimum manifestation onset of acute HAE attack symptoms after the completion of study drug administration.
Time Frame: 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
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.
Time Frame: 1 hour; 4 hours.
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.
Time Frame: 24 hours
24 hours
The rate of attacks that required additional administration of emergency drugs (human C1-esterase inhibitor or icatibant).
Time Frame: 24 hours
24 hours
The rate of attacks that did not respond therapeutically to the study drug administration
Time Frame: 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.
4 hours; 24 hours
The intensity of acute HAE attack symptoms within 24 (twenty-four) hours after study drug administration.
Time Frame: 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
24 hours
Frequency of adverse events.
Time Frame: 14 days
14 days
Frequency of anti-drug antibody formation.
Time Frame: 7 and 14 days
7 and 14 days
The level of anti-drug antibodies neutralizing activity.
Time Frame: 7 and 14 days
Laboratory measurement of antidrug antibody with neutralixing activity.
7 and 14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AO GENERIUM

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.

Helpful Links

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 18, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 21, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 24, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 4, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 21, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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