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Hereditary AngioedemaPhase 2/3NCT04898309

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

A Phase 2/3 study testing GNR-038, 50 МЕ/ kg, GNR-038, 100 МЕ/ kg and Berinert®, 20 МЕ/ kg in people with Hereditary Angioedema, run by AO GENERIUM at 5 sites in Russia.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hereditary Angioedema
What is being tested?
GNR-038, 50 МЕ/ kg, GNR-038, 100 МЕ/ kg and Berinert®, 20 МЕ/ kg
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
5 sitesRussia
Study dates
1 Dec 2021to 31 May 2023
Phase
Phase 2/3
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
Show all 18Show fewer
  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Russia5 sites

  • National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia

    Moscow, 115522

  • Moscow City Clinical Hospital 52

    Moscow, 123182

  • Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology

    Moscow, 630099

  • Rostov State Medical University

    Rostov-on-Don, 344022

  • LLC "Scientific Medical Center of General Therapy and Pharmacology"

    Stavropol, 355000

Other trials in Russia

About this study

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

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

Read the 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.

Being tested
GNR-038, 50 МЕ/ kg, GNR-038, 100 МЕ/ kg, Berinert®, 20 МЕ/ kg, Placebo, GNR-038. The dose will be selected according to results of stage 1 clinical trial.
Keywords
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 Inhibitor Protein, Complement C1 Inactivator Proteins
Medical subject headings
Angioedemas, Hereditary, Genetic Diseases, Inborn, Hypersensitivity, Immune System Diseases, Angioedema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GNR-038, 50 МЕ/ kgDrug

    Also called Recombinant C1 esterase inhibitor, 50 МЕ/ kg

    A single intravenous infusion of GNR-038, 50 МЕ/ kg less than 5 hours after the onset of edema.

  • GNR-038, 100 МЕ/ kgDrug

    Also called Recombinant C1 esterase inhibitor, 100 МЕ/ kg

    A single intravenous infusion of GNR-038, 100 МЕ/ kg less than 5 hours after the onset of edema.

  • Berinert®, 20 МЕ/ kgDrug

    Also called Human C1 esterase inhibitor

    A single intravenous infusion of Berinert®, 20 МЕ/ kg less than 5 hours after the onset of edema.

  • PlaceboDrug

    A single intravenous infusion of Placebo less than 5 hours after the onset of edema.

  • GNR-038. The dose will be selected according to results of stage 1 clinical trial.Drug

    Also called Recombinant C1 esterase inhibitor.

    A single intravenous infusion of GNR-038 less than 5 hours after the onset of edema.

  • Berinert®, 20 МЕ/ kgDrug

    Also called Human C1 esterase inhibitor

    A single intravenous infusion of Berinert®, 20 МЕ/ kg less than 5 hours after the onset of edema.

Study groups in NCT04898309
Study groupRoleWhat they receive
Study stage 1: GNR-038, 50 МЕ/ kgExperimentalRecombinant C1 esterase inhibitor
Receives: Drug: GNR-038, 50 МЕ/ kg
Study stage 1: GNR-038, 100 МЕ/ kgExperimentalRecombinant C1 esterase inhibitor
Receives: Drug: GNR-038, 100 МЕ/ kg
Study stage 1: Berinert®, 20 МЕ/ kgExperimentalHuman C1 esterase inhibitor
Receives: Drug: Berinert®, 20 МЕ/ kg
Study stage 1: PlaceboExperimentalPlacebo
Receives: Drug: Placebo
Study stage 2: GNR-038 in selected doseExperimentalRecombinant C1 esterase inhibitor
Receives: Drug: GNR-038. The dose will be selected according to results of stage 1 clinical trial.
Study stage 2: Berinert®, 20 МЕ/ kgExperimentalHuman C1 esterase inhibitor
Receives: Drug: Berinert®, 20 МЕ/ kg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to symptoms relief onset of acute HAE attack within 24 hours after the end of the drug administration.

    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

    Measured: 24 hours

Secondary outcomes (10)

  1. Time to complete resolution of the symptoms of an acute HAE attack within 24 hours after the end of the study drug administration.

    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

    Measured: 24 hours

  2. Time to minimum manifestation onset of acute HAE attack symptoms after the completion of study drug administration.

    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

    Measured: 24 hours

  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.

    Measured: 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.

    Measured: 24 hours

  5. The rate of attacks that required additional administration of emergency drugs (human C1-esterase inhibitor or icatibant).

    Measured: 24 hours

  6. The rate of attacks that did not respond therapeutically to the study drug administration

    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.

    Measured: 4 hours; 24 hours

  7. The intensity of acute HAE attack symptoms within 24 (twenty-four) hours after study drug administration.

    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

    Measured: 24 hours

  8. Frequency of adverse events.

    Measured: 14 days

  9. Frequency of anti-drug antibody formation.

    Measured: 7 and 14 days

  10. The level of anti-drug antibodies neutralizing activity.

    Laboratory measurement of antidrug antibody with neutralixing activity.

    Measured: 7 and 14 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2021
  2. Study start1 Dec 2021 (estimated)
  3. Primary completion31 May 2023 (estimated)
  4. Study completion31 May 2023 (estimated)

Why it stopped: Company pipeline revision

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
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 blind
Who is masked
Participant, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04898309
Sponsor's protocol ID
CIR-HAE-II-III
Other IDs
#210, April 16, 2
Status last verified
Jan 2022
First submitted
18 May 2021
Last updated
4 Feb 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing GNR-038, 50 МЕ/ kg, GNR-038, 100 МЕ/ kg and Berinert®, 20 МЕ/ kg in people with Hereditary Angioedema, run by AO GENERIUM at 5 sites 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 9 inclusion and 18 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: withdrawn, as of the sponsor's last update on 4 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites 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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 was withdrawn before enrolling participants, so there are no results.

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?

Time to symptoms relief onset of acute HAE attack within 24 hours after the end of the drug administration. (time frame: 24 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04898309.

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 4 Feb 2022.

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