Safety and Efficacy of Interferon-Gamma 1b in Patients With Candidemia

Sponsor
Radboud University Medical Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT04979052
Collaborator
Horizon 2020 - European Commission (Other)
200
5
2
33.6
40
1.2

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Interferon Gamma-1B
Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
200 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Open label adaptive randomized interventional studyOpen label adaptive randomized interventional study
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Safety and Efficacy of Recombinant Interferon-Gamma 1b (rIFN-Gamma 1b) Given With Standard Therapy in Patients With Candidemia
Anticipated Study Start Date :
Mar 15, 2022
Anticipated Primary Completion Date :
Jan 1, 2025
Anticipated Study Completion Date :
Jan 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Interferon-Gamma

Recombinant Interferon-Gamma 1b combined with standard therapy

Drug: Interferon Gamma-1B
100 microgram per day, three times a week, subcutaneous. The duration of the treatment is twelve days or until hospital discharge.
Other Names:
  • Immukin
  • No Intervention: Standard of care

    Standard of care antifungal therapy according tot ESCMID/EFISG (Europe) or ISDA (US) guidelines.

    Outcome Measures

    Primary Outcome Measures

    1. Time to first negative blood culture [Day 14]

    Secondary Outcome Measures

    1. Time to treatment success [Day 14]

      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.

    2. Percentage of patients with mycological outcomes [through intervention completion, an average at day 11 and 2 and 4 weeks after intervention completion]

    3. Percentage of patients with treatment success [through intervention completion, an average at day 11 and 2 and 4 weeks after intervention completion]

    4. Overall survival [Study day 28]

    5. Number of patients with Treatment Emergent Adverse Events (TEAEs). [Study day 49]

    6. Sequential Organ Failure Assessment (SOFA) score [Study day 14]

    7. Adverse events [Study day 14]

    8. Body weight [Study day 49]

      kg

    9. BMI [Study day 49]

      kg/m^2

    10. Prealbumin [Study day 49]

      mg/dl

    11. Total lymphocytes [Study day 49]

      10^9/L

    12. Cholesterol [Study day 49]

      mmol/L

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Duke University Durham North Carolina United States 27708
    2 Klinikum Der Johann Wolfgang Von Goethe Universitaet Frankfurt am main Germany 60590
    3 Radboudumc Nijmegen Gelderland Netherlands 6525 GA
    4 Universitatea de Medicina si Farmacie luliu Hatieganu Cluj-Napoca Romania 400348
    5 Centre Hospitalier Universitaire Vaudois Lausanne Switzerland 1005

    Sponsors and Collaborators

    • Radboud University Medical Center
    • Horizon 2020 - European Commission

    Investigators

    • Principal Investigator: Frank vd Veerdonk, Dr., Radboud University Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Radboud University Medical Center
    ClinicalTrials.gov Identifier:
    NCT04979052
    Other Study ID Numbers:
    • HDM-FUN-Candidemia
    First Posted:
    Jul 27, 2021
    Last Update Posted:
    Mar 15, 2022
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by Radboud University Medical Center
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 15, 2022