IL-1 Receptor Inhibitor for Granulomatous Complications in Patients With Chronic Granulomatous Disease

Sponsor

Federal Research Institute of Pediatric Hematology, Oncology and Immunology (Other)

Overall Status

Completed

CT.gov ID

NCT04136028

Collaborator

(none)

Enrollment

Location

Arm

51.2

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

"Kineret" (INN: Anakinra) neutralizes the biological activity of interleukin-1α (IL-1α) and interleukin-1β (IL-1β) by the concurrent inhibition of binding to interleukin-1 receptor I (IL-1RI). Interleukin-1 (IL-1) is the main pro-inflammatory cytokine that mediates many cellular responses. Anakinra inhibits the reactions caused by IL-1 in vitro, including the induction of nitric oxide and prostaglandin E2 and / or the formation of collagenase by synovial cells, fibroblasts and chondrocytes. According to published data, patients with the chronic granulomatous disease have an increased secretion of interleukin-1, which contributes to the development of granulomatous inflammation. Blocking interleukin-1 reduces the activity of the main pro-inflammatory complex - the inflammasomes, and also restores the autophagy process impaired in patients with chronic granulomatous disease. In this way, inhibition of the IL-1 receptor prevents the activation of innate immunity cells and prevents the maintenance of pathological pro-inflammatory signaling in conditions of IL-1 overproduction. The efficacy and safety of therapy with the above drug is based on the results of international studies on the using of anakinra in patients with chronic granulomatous disease.

Condition or Disease	Intervention/Treatment	Phase
Chronic Granulomatous Disease	Drug: Kineret	Early Phase 1

Detailed Description

The research will include a group of patients with a molecular-genetic confirmed diagnosis of chronic granulomatous disease, which has granulomatous complications on the basis of an initial comprehensive survey.

This examination will include clinical data; laboratory tests - clinical and biochemical analysis of blood (with an assessment of inflammatory activity); molecular-genetic methods for detecting mutations in the genes CYBB, CYBA, NCF2, NCF1 or NCF4; methods for studying the functional activity of neutrophils (chemiluminescence of neutrophils, test with rhodamine); methods for assessing pro-inflammatory interleukins; microbiological testing of bronchoalveolar lavage; histological studу of lung biopsies; as well as the results of visualization techniques (ultrasound investigation of the abdominal organs, CT scan of the chest and abdominal organs). Negative galactomannan and lack of microorganism growth in bronchoalveolar lavage and/or lack of response to complex antibacterial and antifungal therapy for two to three weeks confirm the presence of granulomatous complications in patients. The next step is therapy with an inhibitor of IL-1 receptor (Anakinra). Evaluation of the efficacy and safety therapy is based on the results of control examinations after 3-6 months from the start of treatment and includes an assessment of the level of C-reactive protein and pro-inflammatory cytokines, as well as the results of CT scan of the chest and abdominal organs.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Retrospective Analysis of Efficacy and Safety of Interleukin-1 Receptor Inhibitor for the Treatment of Granulomatous Complications in Patients With Chronic Granulomatous Disease

Actual Study Start Date :

Sep 25, 2015

Actual Primary Completion Date :

Jan 16, 2019

Actual Study Completion Date :

Jan 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: intervention/treatment Anakinra (Kineret)	Drug: Kineret Kineret at a dose of 8 mg/kg per day subcutaneously daily, every day at the same time Other Names: IL-1 receptor inhibitor

Arm

Intervention/Treatment

Experimental: intervention/treatment

Anakinra (Kineret)

Drug: Kineret

Kineret at a dose of 8 mg/kg per day subcutaneously daily, every day at the same time

Other Names:

IL-1 receptor inhibitor

Outcome Measures

Primary Outcome Measures

overall survival [6 months]
Assessment of overall survival in patients with chronic granulomatous disease during therapy with an inhibitor of IL-1 receptor

Secondary Outcome Measures

3 month- event-free survival [3 months]
Assessment of event-free survival in patients with chronic granulomatous disease after treatment of granulomatous complications with an inhibitor of the IL-1 receptor (Anakinra).
6 month-event-free survival [6 months]
Assessment of event-free survival in patients with chronic granulomatous disease after treatment of granulomatous complications with an inhibitor of the IL-1 receptor (Anakinra).

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Granulomatous changes in the lungs or liver according to CT scan.
Negative galactomannan and lack of microorganism growth in bronchoalveolar lavage and/or lack of response to complex antibacterial and antifungal therapy for two to three weeks.
Signed informed consent