Safety and Efficacy of Interferon-Gamma 1b in Patients With Candidemia
Primary Purpose
Candidemia
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Interferon Gamma-1B
Sponsored by
About this trial
This is an interventional treatment trial for Candidemia focused on measuring Interferon Gamma 1b
Eligibility Criteria
Inclusion Criteria:
- Males or non-pregnant females (who must agree to use barrier methods of contraception during the study therapy period, women of childbearing age must have a negative urine pregnancy or serum test at baseline).
- Subjects who are 18 years of age or older.
- Subjects with at least one positive blood culture isolation of Candida species from a specimen drawn within 96 hours prior to study entry.
Subjects who have clinical evidence of infection sometime within 96 hours prior to enrolment, including at least one of the following:
- Temperature >37.8 ˚C on two occasions at least four hours apart or one measurement > 38.2 ˚C
- Systolic blood pressure <90 or a >30 mmHg decrease in systolic blood pressure from the subject's normal baseline or the need for vasopressive therapy.
- Signs of inflammation (swelling, heat, erythema, purulent drainage) from a site infected with Candida (e.g. joint, skin, eye, bone, oesophagus).
- Radiologic findings of invasive candidiasis.
- Subject or their legal representative must sign a written informed consent form.
Exclusion Criteria:
- Subjects with a history of allergy or intolerance to rIFN-γ.
- Subjects with a history of documented epileptic seizures.
- Subjects with severe liver failure ((>5x upper limit AST or ALT or impaired synthesis of proteins such as coagulation factors manifested by increased prothrombin time).
- Women who are pregnant or lactating.
- Subjects who are unlikely to survive more than 24 hours.
- Subjects who have failed previous systemic antifungal therapy for the Candida spp. infection which is being studied.
- Subjects who have received more than 72 hours of systemic antifungal therapy for the current episode, within 96 hours prior to study entry.
Sites / Locations
- Duke University
- Klinikum Der Johann Wolfgang Von Goethe UniversitaetRecruiting
- Hellenic Institute for the Study of Sepsis (HISS)
- RadboudumcRecruiting
- Universitatea de Medicina si Farmacie luliu HatieganuRecruiting
- Centre Hospitalier Universitaire Vaudois
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
No Intervention
Arm Label
Interferon-Gamma
Standard of care
Arm Description
Recombinant Interferon-Gamma 1b combined with standard therapy
Standard of care antifungal therapy according tot ESCMID/EFISG (Europe) or ISDA (US) guidelines.
Outcomes
Primary Outcome Measures
Time to first negative blood culture
Secondary Outcome Measures
Time to treatment success
microbiological eradication of Candida from the blood and any other site of infection; resolution of fever; resolution of other diagnostic variables, such as imaging results, where applicable; and no new signs of infection. The time at which all the variables are met is defined as the date of resolution of infection.
Percentage of patients with mycological outcomes
Percentage of patients with treatment success
Overall survival
Number of patients with Treatment Emergent Adverse Events (TEAEs).
Sequential Organ Failure Assessment (SOFA) score
Adverse events
Body weight
kg
BMI
kg/m^2
Prealbumin
mg/dl
Total lymphocytes
10^9/L
Cholesterol
mmol/L
Full Information
NCT ID
NCT04979052
First Posted
November 9, 2020
Last Updated
June 6, 2023
Sponsor
Radboud University Medical Center
Collaborators
Horizon 2020 - European Commission
1. Study Identification
Unique Protocol Identification Number
NCT04979052
Brief Title
Safety and Efficacy of Interferon-Gamma 1b in Patients With Candidemia
Official Title
Safety and Efficacy of Recombinant Interferon-Gamma 1b (rIFN-Gamma 1b) Given With Standard Therapy in Patients With Candidemia
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 31, 2022 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center
Collaborators
Horizon 2020 - European Commission
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A multi-center open label adaptive randomized interventional phase 2 study to evaluate safety and efficacy of rIFN-y treatment in patiens with candidemia.
Detailed Description
A multi-center open label adaptive randomized interventional phase 2 study to evaluate safety and efficacy of rIFN-y treatment in patiens with candidemia. Patients will be randomized 1:1 between intervention (rIFN-y immunotherapy, subcutaneous dose of 100miicrogram thrice weekly for two weeks or until hospital discharge) in addition to standard of care versus controls (standard of care). Standard of care antifungal therapy is according to ESCMID/EFISG (Europe) or IDSA (US) guidelines. We will assess the effect on clinical outcome and investigate relevant biomarkers that can guide this immunotherapeutic approach.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Candidemia
Keywords
Interferon Gamma 1b
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Open label adaptive randomized interventional study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Interferon-Gamma
Arm Type
Active Comparator
Arm Description
Recombinant Interferon-Gamma 1b combined with standard therapy
Arm Title
Standard of care
Arm Type
No Intervention
Arm Description
Standard of care antifungal therapy according tot ESCMID/EFISG (Europe) or ISDA (US) guidelines.
Intervention Type
Drug
Intervention Name(s)
Interferon Gamma-1B
Other Intervention Name(s)
Immukin
Intervention Description
100 microgram per day, three times a week, subcutaneous. The duration of the treatment is twelve days or until hospital discharge.
Primary Outcome Measure Information:
Title
Time to first negative blood culture
Time Frame
Day 14
Secondary Outcome Measure Information:
Title
Time to treatment success
Description
microbiological eradication of Candida from the blood and any other site of infection; resolution of fever; resolution of other diagnostic variables, such as imaging results, where applicable; and no new signs of infection. The time at which all the variables are met is defined as the date of resolution of infection.
Time Frame
Day 14
Title
Percentage of patients with mycological outcomes
Time Frame
through intervention completion, an average at day 11 and 2 and 4 weeks after intervention completion
Title
Percentage of patients with treatment success
Time Frame
through intervention completion, an average at day 11 and 2 and 4 weeks after intervention completion
Title
Overall survival
Time Frame
Study day 28
Title
Number of patients with Treatment Emergent Adverse Events (TEAEs).
Time Frame
Study day 49
Title
Sequential Organ Failure Assessment (SOFA) score
Time Frame
Study day 14
Title
Adverse events
Time Frame
Study day 14
Title
Body weight
Description
kg
Time Frame
Study day 49
Title
BMI
Description
kg/m^2
Time Frame
Study day 49
Title
Prealbumin
Description
mg/dl
Time Frame
Study day 49
Title
Total lymphocytes
Description
10^9/L
Time Frame
Study day 49
Title
Cholesterol
Description
mmol/L
Time Frame
Study day 49
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males or non-pregnant females (who must agree to use barrier methods of contraception during the study therapy period, women of childbearing age must have a negative urine pregnancy or serum test at baseline).
Subjects who are 18 years of age or older.
Subjects with at least one positive blood culture isolation of Candida species from a specimen drawn within 120 hours prior to study entry.
Subjects who have clinical evidence of infection sometime within 120 hours prior to enrolment, including at least one of the following:
Temperature >37.8 ˚C on two occasions at least four hours apart or one measurement > 38.2 ˚C
Systolic blood pressure <90 or a >30 mmHg decrease in systolic blood pressure from the subject's normal baseline or the need for vassopressive therapy.
Signs of inflammation (swelling, heat, erythema, purulent drainage) from a site infected with Candida (e.g. joint, skin, eye, bone, oesophagus).
Radiologic findings of invasive candidiasis.
Subject or their legal representative must sign a written informed consent form.
In case a patient eligible to participate in this study is incapacitated and as such unable to personally provide informed consent, a written consent form must be signed by their legal representative.
Only incapacitated patients that can be expected to regain the capability to consent will be included in this study. In this case, informed consent will be discussed personally with the study participant after recovery.
The inclusion of incapacitated subjects will only be performed under the above conditions in a country in which such an approach is legal and deemed ethically acceptable.
Exclusion Criteria:
Subjects with a history of allergy or intolerance to rIFN-γ,or any other IMP ingredient or with a history of immediate type hypersensitivity to latex/rubber.
Subjects with a history of documented epileptic seizures.
Subjects with severe liver failure ((>5x upper limit AST or ALT or impaired synthesis of proteins such as coagulation factors manifested by increased prothrombin time).
Treatment with heterologous serum proteins, or immunological preparations such as vaccines, toxins, serums and allergens within three days before trial enrolment.
Women who are pregnant or lactating.
Subjects who are unlikely to survive more than 24 hours.
Subjects who have failed previous systemic antifungal therapy for the Candida spp.
infection which is being studied.
Subjects who have received more than 120 hours of systemic antifungal therapy for the current episode, within 120 hours prior to study entry.
With respect to incapacitated subjects:
Any patient that is deemed incapable of personally providing informed consent due to a neurodegenerative disease, genetic syndrome, and/or perinatal asphyxia, will not be eligible for inclusion in this trial.
Any incapacitated subject that is not expected to recover to a point where they will personally be able to provide informed consent will not be eligible for inclusion in this trial. Patients with renal failure or dialysis do not have a contraindication for treatment with rIFN-y and can be included in this study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Frank vd Veerdonk, Dr.
Phone
0031243618819
Email
frank.vandeveerdonk@radboudumc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank vd Veerdonk, Dr.
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27708
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John R. Perfect, Dr.
Facility Name
Klinikum Der Johann Wolfgang Von Goethe Universitaet
City
Frankfurt am main
ZIP/Postal Code
60590
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Vehreschild, Prof. Dr.
Facility Name
Hellenic Institute for the Study of Sepsis (HISS)
City
Athens
ZIP/Postal Code
11528
Country
Greece
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Evangelos Giamarellos-Bourboulis, Prof. Dr.
Facility Name
Radboudumc
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
6525 GA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frank vd Veerdonk, Prof. Dr.
Facility Name
Universitatea de Medicina si Farmacie luliu Hatieganu
City
Cluj-Napoca
ZIP/Postal Code
400348
Country
Romania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mihaela Sorina Lupse, Dr.
Facility Name
Centre Hospitalier Universitaire Vaudois
City
Lausanne
ZIP/Postal Code
1005
Country
Switzerland
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thierry Calandra, Prof. Dr.
12. IPD Sharing Statement
Plan to Share IPD
No
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Safety and Efficacy of Interferon-Gamma 1b in Patients With Candidemia
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