Hereditary AngioedemaPhase 1NCT04557319
Safety and Pharmacokinetics of GNR-038 in Healthy Volunteers
A Phase 1 study testing GNR-038, 25 МЕ/kg, GNR-038, 50 МЕ/kg and GNR-038, 100 МЕ/kg in people with Hereditary Angioedema, run by AO GENERIUM at 1 site in Russia.
Trial summary
It is an open-label dose-escalating study in sequential cohorts to assess safety and pharmacokinetics of GNR-038. Read more about this study
- Who is it for?
- Ages 18 months to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Hereditary Angioedema
- What is being tested?
- GNR-038, 25 МЕ/kg, GNR-038, 50 МЕ/kg and GNR-038, 100 МЕ/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteRussia
- Study dates
- 10 Mar 2020to 27 Aug 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 months to 50 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Men and women aged 18 to 50 (inclusive) at the time of signing the Informed Consent Form.
- Body mass index (BMI) in the range from 18.5 to 30 kg / m2, body weight from 50 to 90 kg.
- 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.
- Availability of written informed consent obtained from the volunteer prior to any research-related procedures performance.
- Consent to follow the adequate contraceptive methods.
Who cannot join
- Known hypersensitivity to the components of the study drug;
- Burdened allergic history;
- Standard laboratory and instrumental parameters values are outside the normal range;
- Cardiovascular, bronchopulmonary, neuroendocrine systems chronic diseases, as well as gastrointestinal tract, liver, kidneys, hematopoietic, immune systems diseases, mental illness;
- 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.
- Infection with human immunodeficiency virus (HIV), hepatitis B and C;
Show all 17Show fewer
- Acute infectious diseases less than 4 weeks prior to the Screening Visit;
- Regular medication intake less than 2 weeks prior to the Screening Visit;
- For women - the hormonal contraceptives use or hormone replacement therapy for 3 months before the screening period start;
- 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;
- Blood donation (450 ml of blood or plasma and more) less than 3 months before the Screening Visit;
- Participation in clinical trials less than 3 months before the Screening Visit;
- 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;
- Drug addiction, substance abuse, positive urine test for the content of potent and narcotic drugs;
- Smoking more than 10 cigarettes a day;
- Pregnancy or breastfeeding;
- Other reasons that prevent the volunteer from study participating or create an unreasonable risk in the investigator opinion.
Trial locations and contacts
1 site in 1 country.
Russia1 site
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, 117556
About this study
Official title: An Open Study of the Safety and Pharmacokinetics of GNR-038 in Sequential Dose-increase Cohorts in Healthy Volunteers
It is an open-label dose-escalating study in sequential cohorts to assess safety and pharmacokinetics of GNR-038.
Read the 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.
- Conditions
- Hereditary Angioedema
- Being tested
- GNR-038, 25 МЕ/kg, GNR-038, 50 МЕ/kg, GNR-038, 100 МЕ/kg
- Keywords
- 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
- Medical subject headings
- Angioedemas, Hereditary, Angioedema, Vascular Diseases, Cardiovascular Diseases, Urticaria, Skin Diseases, Vascular, Skin Diseases, Hypersensitivity, Immediate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GNR-038, 25 МЕ/kgBiological
Also called rC1inh, 25 МЕ/kg
25 МЕ/kg once per study
GNR-038, 50 МЕ/kgBiological
Also called rC1inh, 50 МЕ/kg
50 МЕ/kg once per study
GNR-038, 100 МЕ/kgBiological
Also called rC1inh, 100 МЕ/kg
100 МЕ/kg once per study
| Study group | Role | What they receive |
|---|---|---|
| GNR-038, 25 МЕ/kg | Experimental | Recombinant C1-esterase (25 ME/kg) inhibitor intravenous infusion Receives: Biological: GNR-038, 25 МЕ/kg |
| GNR-038, 50 МЕ/kg | Experimental | Recombinant C1-esterase (50 ME/kg) inhibitor intravenous infusion Receives: Biological: GNR-038, 50 МЕ/kg |
| GNR-038, 100 МЕ/kg | Experimental | Recombinant C1-esterase (100 ME/kg) inhibitor intravenous infusion Receives: Biological: GNR-038, 100 МЕ/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Adverse Events
Adverse events, Laboratory tests, Vital signs, Physical examination, 12-lead electrocardiogram, Allergic associated reaction, Infusion associated reaction, Antidrug antibody.
Measured: 28 Days
Secondary outcomes (7)
Peak Plasma Concentration (Cmax)
Pharmacokinetic parameters
Measured: 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
Area under the plasma concentration versus time curve (AUC)
Pharmacokinetic parameters
Measured: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Half-life (T1/2)
Pharmacokinetic parameters
Measured: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Elimination rate constant (Kel)
Pharmacokinetic parameters
Measured: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Mean retention time (MRT)
Pharmacokinetic parameters
Measured: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Overall clearance (Cl)
Pharmacokinetic parameters
Measured: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Kinetic volume of distribution (Vz)
Pharmacokinetic parameters
Measured: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2020
- Study start10 Mar 2020
- Primary completion27 Aug 2020
- Study completion27 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary AngioedemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Sequential dose-increase cohorts in healthy volunteers
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- AO GENERIUM
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Oksana A. Markova, MD, Study chair, AO GENERIUM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04557319
- Sponsor's protocol ID
- CIR-HAET-I
- Other IDs
- #725 eff date 20.12.2019
- Status last verified
- Aug 2020
- First submitted
- 26 Aug 2020
- Last updated
- 30 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Study of the Safety and Pharmacokinetics of GNR-038 in Sequential Dose-increase Cohorts in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT04557319
- Acronym / sponsor ID
- CIR-HAET-I
- Conditions
- Hereditary Angioedema
- Keywords
- Angioedema, Angioedemas, Hereditary, Vascular Diseases, Cardiovascular Diseases, Urticaria, Skin Diseases, Vascular, Skin Diseases, Hypersensitivity, Immediate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- AO GENERIUMIndustry (pharma, biotech, devices)
- Study start
- 10 Mar 2020 (actual)
- Primary completion
- 27 Aug 2020 (actual)
- Study completion
- 27 Aug 2020 (actual)
- First posted
- 21 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
It is an open-label dose-escalating study in sequential cohorts to assess safety and pharmacokinetics of GNR-038.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Sequential dose-increase cohorts in healthy volunteers
| Arm | Type | Receives |
|---|---|---|
| GNR-038, 25 МЕ/kg | Experimental | Biological: GNR-038, 25 МЕ/kgRecombinant C1-esterase (25 ME/kg) inhibitor intravenous infusion |
| GNR-038, 50 МЕ/kg | Experimental | Biological: GNR-038, 50 МЕ/kgRecombinant C1-esterase (50 ME/kg) inhibitor intravenous infusion |
| GNR-038, 100 МЕ/kg | Experimental | Biological: GNR-038, 100 МЕ/kgRecombinant C1-esterase (100 ME/kg) inhibitor intravenous infusion |
Who may qualify
- Ages
- 18 months to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Men and women aged 18 to 50 (inclusive) at the time of signing the Informed Consent Form.
- Body mass index (BMI) in the range from 18.5 to 30 kg / m2, body weight from 50 to 90 kg.
- 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.
- Availability of written informed consent obtained from the volunteer prior to any research-related procedures performance.
- Consent to follow the adequate contraceptive methods.
Key exclusion criteria (17 listed)
- Known hypersensitivity to the components of the study drug;
- Burdened allergic history;
- Standard laboratory and instrumental parameters values are outside the normal range;
- Cardiovascular, bronchopulmonary, neuroendocrine systems chronic diseases, as well as gastrointestinal tract, liver, kidneys, hematopoietic, immune systems diseases, mental illness;
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GNR-038, 25 МЕ/kgAlso: rC1inh, 25 МЕ/kg25 МЕ/kg once per study | Biological | GNR-038, 25 МЕ/kg |
| GNR-038, 50 МЕ/kgAlso: rC1inh, 50 МЕ/kg50 МЕ/kg once per study | Biological | GNR-038, 50 МЕ/kg |
| GNR-038, 100 МЕ/kgAlso: rC1inh, 100 МЕ/kg100 МЕ/kg once per study | Biological | GNR-038, 100 МЕ/kg |
Primary outcome
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.
7 secondary outcomes
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
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
Half-life (T1/2)
Time frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Elimination rate constant (Kel)
Time frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Mean retention time (MRT)
Time frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Overall clearance (Cl)
Time frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Kinetic volume of distribution (Vz)
Time frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2020.
- Individual participant dataSharing planned: No
Related trials for Hereditary Angioedema
RecruitingPhase 3
Donidalorsen Treatment in Children With Hereditary Angioedema
Hereditary Angioedema (HAE)
RecruitingObservational study
A Study of Takhzyro in Teenagers and Adults With Hereditary Angioedema (HAE) in South Korea
Hereditary Angioedema (HAE)
Active, not recruitingPhase 3
HAELO: A Phase 3 Study to Evaluate NTLA-2002 in Participants With Hereditary Angioedema (HAE)
Hereditary Angioedema
RecruitingPhase 3
Study of IV Human Plasma-derived C1 Esterase Inhibitor Concentrate in Patients With Congenital C1-INH Deficiency for Treatment and Pre-procedure Preventing of Acute Hereditary Angioedema Attacks
Acute Hereditary Angio Edema
Active, not recruitingPhase 1/2
NTLA-2002 in Adults With Hereditary Angioedema (HAE)
Hereditary Angioedema
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Oksana A. Markova, MD study chair
AO GENERIUM
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GNR-038, 25 МЕ/kg, GNR-038, 50 МЕ/kg and GNR-038, 100 МЕ/kg in people with Hereditary Angioedema, run by AO GENERIUM at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with Adverse Events (time frame: 28 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2020.