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NCT Number: NCT04136028

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

"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.

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Key information

Conditions

Chronic Granulomatous Disease Chronic Disease Congenital, Hereditary, and Neonatal Diseases and Abnormalities Disease Attributes Genetic Diseases, Inborn Genetic Diseases, X-Linked Granulomatous Disease, Chronic Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunologic Deficiency Syndromes Leukocyte Disorders Pathologic Processes Pathological Conditions, Signs and Symptoms Phagocyte Bactericidal Dysfunction

Age range

Up to 18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

Moscow, 117198, Russia

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Kineret

Drug

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

Other names: IL-1 receptor inhibitor

Primary outcomes

  1. overall survival

    Time frame: 6 months

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

Secondary outcomes

  1. 3 month- event-free survival

    Time frame: 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).

  2. 6 month-event-free survival

    Time frame: 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).

Sponsors and collaborators

Lead sponsor

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Other

Registry information

Official study 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

Important dates

Study start
2015
Primary completion
2019
Study completion
2020
First posted
Oct 23, 2019
Registry last updated
Apr 7, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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