E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Systemic fungal infection |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to evaluate the efficacy and safety and rIFN-γ as adjunctive treatment in combination with standard therapy for the treatment of patients with candidemia. Efficacy is defined as clearance of candidemia within the first 7 days of treatment, taking into account mortality.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: •To evaluate new markers that could be used to identify patients that respond to immunotherapy with rIFN-γ. •To identify markers that can monitor the patient’s immunological and clinical response to rIFN-γ immunotherapy. •To perform mechanistic studies to further elucidate mechanisms that are important for host defence against candidemia and the effects of rIFN-γ on these mechanisms.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 at some time 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 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.
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E.4 | Principal 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 late/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 72 hours of systemic antifungal therapy for the current episode, within 96 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 parinatal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to first negative blood culture |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The time to treatment success (resolution of infection). To achieve this endpoint of resolution of infection, the following criteria are to be met: 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. Treatment is considered to have failed if new signs of disease have emerged, when none of the other criteria of resolution have been met, when antifungal treatment is changed for any reason, or when a patient withdraws from the study before resolution of infection has been documented. Cases are scored to have improved if no new signs of disease are present and at least one of the other criteria of resolution has been met. - 2. Percentage of patients with Mycological Outcomes at end of study treatment (EOST), end of treatment (EOT), and 2 and 4 weeks after end of treatment (EOT). - 3. Percentage of patients with Treatment Success at end of treatment (EOT), and 2 and 4 weeks after end of treatment (EOT). - 4. Overall survival at Study Day 30. - 5. Number of patients with Treatment Emergent Adverse Events (TEAEs). (Time frame 49 days) - 6. Evaluation of patient status at end of rIFN-γ treatment including organ (dys)function (Sequential Organ Failure Assessment [SOFA] score), and adverse events. (Time frame 14 days) - 7. Nutritional status (body weight, BMI), nutritional blood parameters (prealbumin, total lymphocytes, cholesterol). (Time frame 49 days) 8. Genetics and transcriptomics 9. Gut microbiota composition and Candida genomics and metabolomics.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
Netherlands |
Romania |
Switzerland |
Germany |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |