rIFN-Gamma 1b in Candidemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Radboud University Medical Center

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

8 Nov 2024 → 30 Mar 2026

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Horizon 2020

External identifiers

EU CT number

2024-510816-55-00

EudraCT number

2020-003204-13

ClinicalTrials.gov

NCT04979052

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The primary objective of the study is to evaluate the efficacy and safety of 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.

Secondary objectives 3

1. To evaluate new markers that could be used to identify patients that respond to immunotherapy with rIFN-γ.
2. To identify markers that can monitor the patient’s immunological and clinical response to rIFN-γ immunotherapy.
3. 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.

Conditions and MedDRA coding

Candidemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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).
2. Subjects who are 18 years of age or older.
3. Subjects with at least one positive blood culture isolation of Candida species from a specimen drawn within 120 hours prior to study entry.
4. 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.
5. Subject or their legal representative must sign a written informed consent form

Exclusion criteria 10

1. 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.
2. Subjects with a history of documented epileptic seizures.
3. 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)
4. Treatment with heterologous serum proteins, or immunological preparations such as vaccines, toxins, serums and allergens within three days before trial enrolment.
5. Women who are pregnant or lactating.
6. Subjects who are unlikely to survive more than 24 hours.
7. Subjects who have failed previous systemic antifungal therapy for the Candida spp. infection which is being studied.
8. Subjects who have received more than 120 hours of systemic antifungal therapy for the current episode, within 120 hours prior to study entry.
9. 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.
10. Patients with renal failure or dialysis do not have a contraindication for treatment with rIFNy and can be included in this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first negative blood culture.

Secondary endpoints 10

1. Time of resolution to infection (composite endpoint).
2. Percentage of patients with mycological outcomes at EOST, EOT, and day 14 and day 28 after EOT.
3. Percentage of patients with treatment success at EOST, EOT, and day 14 and day 28 after EOT.
4. Overall survival at Study Day 28.
5. Number of patients with Treatment Emergent Adverse Events (TEAEs).
6. Evaluation of patient status at end of rIFN-γ treatment including organ (dys)function (Sequential Organ Failure Assessment [SOFA] score), and adverse events
7. Nutritional status (body weight, BMI), nutritional blood parameters (prealbumin, total lymphocytes, cholesterol).
8. Genetics and transcriptomics.
9. Gut microbiota composition and Candida genomics and metabolomics
10. Changes in circulating cytokines, biomarkers, LAP activation, inflammasome, and immunoprofiling.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Radboud University Medical Center

Sponsor organisation

Stichting Radboud University Medical Center

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Stichting Radboud University Medical Center

Contact name

Frank van de Veerdonk

Public contact point

Organisation

Stichting Radboud University Medical Center

Contact name

Frank van de Veerdonk

Third parties 1

Locations

4 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications