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

Safety and Efficacy of Recombinant Interferon-Gamma 1b (rIFN-Gamma 1b) Given With Standard Therapy in Patients With Candidemia

A multi-center open label adaptive randomized interventional phase 2 study to evaluate safety and efficacy of rIFN-y treatment in patiens with candidemia.

Study Overview

• Status: Recruiting
• Conditions: Candidemia
• Intervention / Treatment: Drug: Interferon Gamma-1B

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 Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Frank vd Veerdonk, Dr.; Phone Number: 0031243618819; Email: frank.vandeveerdonk@radboudumc.nl

Study Locations

• Germany
  • Frankfurt am main, Germany, 60590
    • Recruiting
    • Klinikum Der Johann Wolfgang Von Goethe Universitaet
    • Contact: Maria Vehreschild, Prof. Dr.
• Greece
  • Athens, Greece, 11528
    • Recruiting
    • Hellenic Institute for the Study of Sepsis (HISS)
    • Contact: Evangelos Giamarellos-Bourboulis, Prof. Dr.
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Recruiting
      • Radboudumc
      • Contact: Frank vd Veerdonk, Prof. Dr.
• Romania
  • Cluj-Napoca, Romania, 400348
    • Recruiting
    • Universitatea de Medicina si Farmacie luliu Hatieganu
    • Contact: Mihaela Sorina Lupse, Dr.
• Switzerland
  • Lausanne, Switzerland, 1005
    • Not yet recruiting
    • Centre Hospitalier Universitaire Vaudois
    • Contact: Thierry Calandra, Prof. Dr.
• United States
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Not yet recruiting
      • Duke University
      • Contact: John R. Perfect, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to first negative blood culture	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 14
Percentage of patients with mycological outcomes		through intervention completion, an average at day 11 and 2 and 4 weeks after intervention completion
Percentage of patients with treatment success		through intervention completion, an average at day 11 and 2 and 4 weeks after intervention completion
Overall survival		Study day 28
Number of patients with Treatment Emergent Adverse Events (TEAEs).		Study day 49
Sequential Organ Failure Assessment (SOFA) score		Study day 14
Adverse events		Study day 14
Body weight	kg	Study day 49
BMI	kg/m^2	Study day 49
Prealbumin	mg/dl	Study day 49
Total lymphocytes	10^9/L	Study day 49
Cholesterol	mmol/L	Study day 49

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Horizon 2020 - European Commission
• Investigators: Principal Investigator: Frank vd Veerdonk, Dr., Radboud university medical center

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2022
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: July 16, 2021
• First Posted (Actual): July 27, 2021

Study Record Updates

• Last Update Posted (Estimated): November 3, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Interferon Gamma 1b
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Sepsis; Mycoses; Invasive Fungal Infections; Fungemia; Candidiasis; Candidiasis, Invasive; Candidemia; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Interferons; Interferon-gamma
• Other Study ID Numbers: HDM-FUN-Candidemia

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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