Chronic Granulomatous DiseaseEarly Phase 1NCT04136028
IL-1 Receptor Inhibitor for Granulomatous Complications in Patients With Chronic Granulomatous Disease
A Early Phase 1 study testing Kineret in people with Chronic Granulomatous Disease, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Chronic Granulomatous Disease
- What is being tested?
- Kineret
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteRussia
- Study dates
- 25 Sep 2015to Jan 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- Patients, who do not meet the inclusion criteria.
- The reluctance of the patient or his legal representatives to participate in the research.
Trial locations and contacts
1 site in 1 country.
Russia1 site
Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
Moscow, 117198
About this study
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
"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.
Read the 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.
- Conditions
- Chronic Granulomatous Disease
- Being tested
- Kineret
- Keywords
- Chronic Granulomatous Disease, Anakinra, Kineret
- Medical subject headings
- Granulomatous Disease, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KineretDrug
Also called IL-1 receptor inhibitor
Kineret at a dose of 8 mg/kg per day subcutaneously daily, every day at the same time
| Study group | Role | What they receive |
|---|---|---|
| intervention/treatment | Experimental | Anakinra (Kineret) Receives: Drug: Kineret |
What is being measured
The primary outcome is the main question the study is designed to answer.
overall survival
Assessment of overall survival in patients with chronic granulomatous disease during therapy with an inhibitor of IL-1 receptor
Measured: 6 months
Secondary outcomes (2)
3 month- event-free survival
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).
Measured: 3 months
6 month-event-free survival
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).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2019
- Study start25 Sep 2015
- Primary completion16 Jan 2019
- Study completionJan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Granulomatous DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and Immunology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anna Shcherbina, PhD, Principal investigator, National Research Center for Pediatric Hematology , Moscow, Russian Federation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04136028
- Sponsor's protocol ID
- NCPHOI-2019-05
- Status last verified
- Apr 2020
- First submitted
- 21 Oct 2019
- Last updated
- 7 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 24879159de 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.
PubMed 24550444Hahn 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.
PubMed 26052777Meissner 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.
PubMed 20495074
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04136028
- Acronym / sponsor ID
- NCPHOI-2019-05
- Conditions
- Chronic Granulomatous Disease
- Keywords
- Chronic Granulomatous Disease, Anakinra, Kineret
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (estimated)
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and ImmunologyUniversity, hospital or other
- Study start
- 25 Sep 2015 (actual)
- Primary completion
- 16 Jan 2019 (actual)
- Study completion
- Jan 2020 (actual)
- First posted
- 23 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
"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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| intervention/treatment | Experimental | Drug: KineretAnakinra (Kineret) |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- Patients, who do not meet the inclusion criteria.
- The reluctance of the patient or his legal representatives to participate in the research.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KineretAlso: IL-1 receptor inhibitorKineret at a dose of 8 mg/kg per day subcutaneously daily, every day at the same time | Drug | intervention/treatment |
Primary outcome
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
2 secondary outcomes
3 month- event-free survival
Time frame: 3 months
6 month-event-free survival
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2020.
- Background: PubMed 24879159van 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.
- Background: PubMed 24550444de 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.
- Background: PubMed 26052777Hahn 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.
- Background: PubMed 20495074Meissner 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anna Shcherbina, PhD principal investigator
National Research Center for Pediatric Hematology , Moscow, Russian Federation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Kineret in people with Chronic Granulomatous Disease, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
overall survival (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04136028, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2020.