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

Hereditary Angioedema Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04898309
• Other study ID #: CIR-HAE-II-III
• Secondary ID: #210, April 16,
• Status: Withdrawn
• Phase: Phase 2/Phase 3
• Start date: December 1, 2021
• Est. completion date: May 31, 2023

Study information

• Verified date: January 2022
• Source: AO GENERIUM
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 31, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

Drug:
• GNR-038, 50 ??/ kg
A single intravenous infusion of GNR-038, 50 ??/ kg less than 5 hours after the onset of edema.
• GNR-038, 100 ??/ kg
A single intravenous infusion of GNR-038, 100 ??/ kg less than 5 hours after the onset of edema.
• Berinert®, 20 ??/ kg
A single intravenous infusion of Berinert®, 20 ??/ kg less than 5 hours after the onset of edema.
• Placebo
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.
A single intravenous infusion of GNR-038 less than 5 hours after the onset of edema.
• Berinert®, 20 ??/ kg
A single intravenous infusion of Berinert®, 20 ??/ kg less than 5 hours after the onset of edema.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AO GENERIUM

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	24 hours
Secondary	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	24 hours
Secondary	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	24 hours
Secondary	The proportion of HAE exacerbation episodes that achieved symptom relief after 1 hour and 4 (four) hours after the end of study drug administration.		1 hour; 4 hours.
Secondary	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.		24 hours
Secondary	The rate of attacks that required additional administration of emergency drugs (human C1-esterase inhibitor or icatibant).		24 hours
Secondary	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.	4 hours; 24 hours
Secondary	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	24 hours
Secondary	Frequency of adverse events.		14 days
Secondary	Frequency of anti-drug antibody formation.		7 and 14 days
Secondary	The level of anti-drug antibodies neutralizing activity.	Laboratory measurement of antidrug antibody with neutralixing activity.	7 and 14 days

External Links

•   Clinical trial registry
•   Clinical trial registry, Ministry of Health of Russian Federation