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Trial record 20 of 56 for:    Ruconest

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04898309
Recruitment Status : Withdrawn (Company pipeline revision)
First Posted : May 24, 2021
Last Update Posted : February 4, 2022
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Hereditary Angioedema Drug: GNR-038, 50 МЕ/ kg Drug: GNR-038, 100 МЕ/ kg Drug: Berinert®, 20 МЕ/ kg Drug: Placebo Drug: GNR-038. The dose will be selected according to results of stage 1 clinical trial. Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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
Masking: Double (Participant, Investigator)
Masking Description: At the first stage - the study will be blinded, at the second stage - open-label
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : December 1, 2021
Estimated Primary Completion Date : May 31, 2023
Estimated Study Completion Date : May 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Human C1 esterase inhibitor




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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. ]
  4. 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 ]
  5. The rate of attacks that required additional administration of emergency drugs (human C1-esterase inhibitor or icatibant). [ Time Frame: 24 hours ]
  6. 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.

  7. 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

  8. Frequency of adverse events. [ Time Frame: 14 days ]
  9. Frequency of anti-drug antibody formation. [ Time Frame: 7 and 14 days ]
  10. The level of anti-drug antibodies neutralizing activity. [ Time Frame: 7 and 14 days ]
    Laboratory measurement of antidrug antibody with neutralixing activity.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04898309


Locations
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Russian Federation
National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia
Moscow, Russian Federation, 115522
Moscow City Clinical Hospital 52
Moscow, Russian Federation, 123182
Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology
Moscow, Russian Federation, 630099
Rostov State Medical University
Rostov-on-Don, Russian Federation, 344022
LLC "Scientific Medical Center of General Therapy and Pharmacology"
Stavropol', Russian Federation, 355000
Sponsors and Collaborators
AO GENERIUM
Investigators
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Study Chair: Oksana A. Markova, MD AO GENERIUM
Additional Information:
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Responsible Party: AO GENERIUM
ClinicalTrials.gov Identifier: NCT04898309    
Other Study ID Numbers: CIR-HAE-II-III
#210, April 16, 2 ( Other Identifier: Ministry of Health of Russian Federation )
First Posted: May 24, 2021    Key Record Dates
Last Update Posted: February 4, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AO GENERIUM:
Complement C1 Inhibitor Protein
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 Inactivator Proteins
Additional relevant MeSH terms:
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Complement C1 Inhibitor Protein
Angioedema
Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Hereditary Complement Deficiency Diseases
Primary Immunodeficiency Diseases
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Complement C1s
Complement C1 Inactivator Proteins
Immunologic Factors
Physiological Effects of Drugs
Complement Inactivating Agents
Immunosuppressive Agents