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

Early Phase 1

Completed

• Conditions: Chronic Granulomatous Disease
• Interventions: Drug: Kineret

• Registration Number: NCT04136028
• Lead Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

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.

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 Timeline

• Study Start: 2015-09-25
• Primary Completion: 2019-01-16
• Study First Submitted: 2019-10-21
• Study First Submitted QC: 2019-10-22
• Study First Posted: 2019-10-23
• Study Completion: 2020-01
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-06
• Last Update Posted: 2020-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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

Exclusion Criteria

• Patients, who do not meet the inclusion criteria.
• The reluctance of the patient or his legal representatives to participate in the research.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
intervention/treatment	Kineret	Anakinra (Kineret)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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).
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).

Trial Locations

Locations (1)

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology; 🇷🇺 Moscow, Russian Federation