Clinical trial NCT04979052: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Candidemia
Keywords: Interferon Gamma 1b
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Horizon 2020 - European Commission
First posted: 2021-07-27
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open label adaptive randomized interventional study
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Time to first negative blood culture
timeFrame: Day 14
Secondary outcomes:
measure: Time to treatment success
timeFrame: Day 14
measure: Percentage of patients with mycological outcomes
timeFrame: through intervention completion, an average at day 11 and 2 and 4 weeks after intervention completion
measure: Percentage of patients with treatment success
timeFrame: through intervention completion, an average at day 11 and 2 and 4 weeks after intervention completion
measure: Overall survival
timeFrame: Study day 28
measure: Number of patients with Treatment Emergent Adverse Events (TEAEs).
timeFrame: Study day 49
measure: Sequential Organ Failure Assessment (SOFA) score
timeFrame: Study day 14
measure: Adverse events
timeFrame: Study day 14
measure: Body weight
timeFrame: Study day 49
measure: BMI
timeFrame: Study day 49
measure: Prealbumin
timeFrame: Study day 49
measure: Total lymphocytes
timeFrame: Study day 49
measure: Cholesterol
timeFrame: Study day 49
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Frankfurt am main
country: Germany
facility: Klinikum Der Johann Wolfgang Von Goethe Universitaet
city: Athens
country: Greece
facility: Hellenic Institute for the Study of Sepsis (HISS)
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
city: Cluj-Napoca
country: Romania
facility: Universitatea de Medicina si Farmacie luliu Hatieganu
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
Study officials:
affiliation: Radboud University Medical Center
name: Frank vd Veerdonk, Dr.
role: PRINCIPAL_INVESTIGATOR
References: