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Safety and Pharmacokinetics of GNR-038 in Healthy Volunteers

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: NCT04557319
Recruitment Status : Completed
First Posted : September 21, 2020
Last Update Posted : September 30, 2020
Sponsor:
Information provided by (Responsible Party):
AO GENERIUM

Brief Summary:
It is an open-label dose-escalating study in sequential cohorts to assess safety and pharmacokinetics of GNR-038.

Condition or disease Intervention/treatment Phase
Hereditary Angioedema Biological: GNR-038, 25 МЕ/kg Biological: GNR-038, 50 МЕ/kg Biological: GNR-038, 100 МЕ/kg Phase 1

Detailed Description:

Hereditary angioedema (HAE) is a rare potentially life-threatening genetically determined disease associated with a deficiency or impairment of C1 esterase inhibitor (C1 inhibitor) functional activity. Main clinical manifestations of HAE are recurrent mucous membranes edema and localization of the derma deep layers. Attack persist from several hours to several days and disappear without a trace in most cases, without additional therapy.

The prevalence of the disease in the world is from 1:10 000 to 1: 150 000. The plasma/recombinant C1 inhibitor use to compensate for its deficiency or insufficient functional activity in patients with HAE is recommended both for severe and for long-term and short-term (before surgical interventions and dental manipulations) prophylaxis.

GNR-038 is a recombinant C1 inhibitor (rhC1-inh), which is a complete structural and functional analogue of the plasma C1 inhibitor.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Sequential dose-increase cohorts in healthy volunteers
Masking: None (Open Label)
Primary Purpose: Other
Official Title: An Open Study of the Safety and Pharmacokinetics of GNR-038 in Sequential Dose-increase Cohorts in Healthy Volunteers
Actual Study Start Date : March 10, 2020
Actual Primary Completion Date : August 27, 2020
Actual Study Completion Date : August 27, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GNR-038, 25 МЕ/kg
Recombinant C1-esterase (25 ME/kg) inhibitor intravenous infusion
Biological: GNR-038, 25 МЕ/kg
25 МЕ/kg once per study
Other Name: rC1inh, 25 МЕ/kg

Experimental: GNR-038, 50 МЕ/kg
Recombinant C1-esterase (50 ME/kg) inhibitor intravenous infusion
Biological: GNR-038, 50 МЕ/kg
50 МЕ/kg once per study
Other Name: rC1inh, 50 МЕ/kg

Experimental: GNR-038, 100 МЕ/kg
Recombinant C1-esterase (100 ME/kg) inhibitor intravenous infusion
Biological: GNR-038, 100 МЕ/kg
100 МЕ/kg once per study
Other Name: rC1inh, 100 МЕ/kg




Primary Outcome Measures :
  1. Number of participants with Adverse Events [ Time Frame: 28 Days ]
    Adverse events, Laboratory tests, Vital signs, Physical examination, 12-lead electrocardiogram, Allergic associated reaction, Infusion associated reaction, Antidrug antibody.


Secondary Outcome Measures :
  1. Peak Plasma Concentration (Cmax) [ Time Frame: 45, 30 and 15 minutes before GNR-038 infusion; 0, 15, 30 minutes, 1, 2, 4, 8,12,16, 24, 48, 72, 96, 120,144 and 168 hours after GNR-038 infusion ]
    Pharmacokinetic parameters

  2. Area under the plasma concentration versus time curve (AUC) [ Time Frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 ]
    Pharmacokinetic parameters

  3. Half-life (T1/2) [ Time Frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 ]
    Pharmacokinetic parameters

  4. Elimination rate constant (Kel) [ Time Frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 ]
    Pharmacokinetic parameters

  5. Mean retention time (MRT) [ Time Frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 ]
    Pharmacokinetic parameters

  6. Overall clearance (Cl) [ Time Frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 ]
    Pharmacokinetic parameters

  7. Kinetic volume of distribution (Vz) [ Time Frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 ]
    Pharmacokinetic parameters



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Months to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  1. Men and women aged 18 to 50 (inclusive) at the time of signing the Informed Consent Form.
  2. Body mass index (BMI) in the range from 18.5 to 30 kg / m2, body weight from 50 to 90 kg.
  3. The diagnosis is "healthy" according to the data of clinical and biochemical blood tests, urinalysis, results of physical examination, measurement of vital signs, results of electrocardiography.
  4. Availability of written informed consent obtained from the volunteer prior to any research-related procedures performance.
  5. Consent to follow the adequate contraceptive methods.

Exclusion Criteria

  1. Known hypersensitivity to the components of the study drug;
  2. Burdened allergic history;
  3. Standard laboratory and instrumental parameters values are outside the normal range;
  4. Cardiovascular, bronchopulmonary, neuroendocrine systems chronic diseases, as well as gastrointestinal tract, liver, kidneys, hematopoietic, immune systems diseases, mental illness;
  5. Diseases and conditions associated with thrombosis (myocardial infarction, transient ischemic attacks, deep and superficial vein thrombosis, pulmonary embolism) less than 6 months before the screening period start, as well as an increased risk of arterial or venous thrombosis according to the investigator opinion.
  6. Infection with human immunodeficiency virus (HIV), hepatitis B and C;
  7. Acute infectious diseases less than 4 weeks prior to the Screening Visit;
  8. Regular medication intake less than 2 weeks prior to the Screening Visit;
  9. For women - the hormonal contraceptives use or hormone replacement therapy for 3 months before the screening period start;
  10. Systolic pressure less than 100 mmHg or above 140 mmHg; diastolic pressure less than 70 mmHg or above 90 mmHg; pulse rate less than 60 beats/min or more than 90 beats/min;
  11. Blood donation (450 ml of blood or plasma and more) less than 3 months before the Screening Visit;
  12. Participation in clinical trials less than 3 months before the Screening Visit;
  13. More than 10 alcohol units intake per week (1 unit of alcohol is equivalent to 1/2 liter of beer, 200 ml of wine or 50 ml of ethanol) OR anamnestic information about alcoholism, detection of ethanol in exhaled air;
  14. Drug addiction, substance abuse, positive urine test for the content of potent and narcotic drugs;
  15. Smoking more than 10 cigarettes a day;
  16. Pregnancy or breastfeeding;
  17. Other reasons that prevent the volunteer from study participating or create an unreasonable risk in the investigator opinion.

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): NCT04557319


Locations
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Russian Federation
State budgetary institution of healthcare of the city of Moscow "Сity polyclinic No. 2 of the Department of healthcare of the city of Moscow"
Moscow, Russian Federation, 117556
Sponsors and Collaborators
AO GENERIUM
Investigators
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Study Chair: Oksana A. Markova, MD AO GENERIUM
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Responsible Party: AO GENERIUM
ClinicalTrials.gov Identifier: NCT04557319    
Other Study ID Numbers: CIR-HAET-I
#725 eff date 20.12.2019 ( Other Identifier: Clinical trial approval number, Ministry of Health of Russia )
First Posted: September 21, 2020    Key Record Dates
Last Update Posted: September 30, 2020
Last Verified: August 2020
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:
Angioedema
Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Genetic Diseases, Inborn
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Additional relevant MeSH terms:
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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