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

NCT04136028 | Completed Early Phase 1

• 1 other identifier: NCPHOI-2019-05
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Granulomatous Disease

Keywords

Chronic Granulomatous Disease; Anakinra; Kineret

Outcome Measures

Primary Outcomes (1)

• overall survival

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

  6 months

Secondary Outcomes (2)

• 3 month- event-free survival

  3 months

• 6 month-event-free survival

  6 months

Study Arms (1)

intervention/treatment

EXPERIMENTAL

Anakinra (Kineret)

Drug: Kineret

Interventions

Kineret DRUG

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

Also known as: IL-1 receptor inhibitor

intervention/treatment

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• The reluctance of the patient or his legal representatives to participate in the research.

Sponsors & Collaborators

• Federal Research Institute of Pediatric Hematology, Oncology and Immunology: lead

Study Sites (1)

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

Moscow, 117198, Russia

Location

Related Publications (4)

• van de Veerdonk FL, Dinarello CA. Deficient autophagy unravels the ROS paradox in chronic granulomatous disease. Autophagy. 2014 Jun;10(6):1141-2. doi: 10.4161/auto.28638.

  PMID: 24879159 BACKGROUND

• de Luca A, Smeekens SP, Casagrande A, Iannitti R, Conway KL, Gresnigt MS, Begun J, Plantinga TS, Joosten LA, van der Meer JW, Chamilos G, Netea MG, Xavier RJ, Dinarello CA, Romani L, van de Veerdonk FL. IL-1 receptor blockade restores autophagy and reduces inflammation in chronic granulomatous disease in mice and in humans. Proc Natl Acad Sci U S A. 2014 Mar 4;111(9):3526-31. doi: 10.1073/pnas.1322831111. Epub 2014 Feb 18.

  PMID: 24550444 BACKGROUND

• Hahn KJ, Ho N, Yockey L, Kreuzberg S, Daub J, Rump A, Marciano BE, Quezado M, Malech HL, Holland SM, Heller T, Zerbe CS. Treatment With Anakinra, a Recombinant IL-1 Receptor Antagonist, Unlikely to Induce Lasting Remission in Patients With CGD Colitis. Am J Gastroenterol. 2015 Jun;110(6):938-9. doi: 10.1038/ajg.2015.135. No abstract available.

  PMID: 26052777 BACKGROUND

• Meissner F, Seger RA, Moshous D, Fischer A, Reichenbach J, Zychlinsky A. Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease. Blood. 2010 Sep 2;116(9):1570-3. doi: 10.1182/blood-2010-01-264218. Epub 2010 May 21.

  PMID: 20495074 BACKGROUND

MeSH Terms

Conditions

Granulomatous Disease, Chronic

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Anna Shcherbina, PhD

  National Research Center for Pediatric Hematology , Moscow, Russian Federation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2019
• First Posted: October 23, 2019
• Study Start: September 25, 2015
• Primary Completion: January 16, 2019
• Study Completion: January 1, 2020
• Last Updated: April 7, 2020

Record last verified: 2020-04

Locations

RU (1)