Interferon Gamma-1B for Candida Blood Infection

(HDM-FUN Cand Trial)

Recruiting at 6 trial locations

Overseen By Frank vd Veerdonk, Dr.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Radboud University

Must not be taking: Vaccines, Toxins

Disqualifiers: Epileptic seizures, Severe liver failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Interferon Gamma-1B, a type of immunotherapy, to determine its safety and effectiveness for people with candidemia, a blood infection caused by Candida yeast. Participants will receive either this new treatment combined with standard antifungal therapy or the standard treatment alone. Ideal participants have had at least one positive blood test for Candida and show signs of infection, such as fever or low blood pressure. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have been treated with certain immune-related therapies or antifungal treatments recently, you may not be eligible to participate.

Is there any evidence suggesting that Interferon Gamma-1B is likely to be safe for humans?

Research has shown that Interferon Gamma-1B has been tested in people for various conditions, such as a type of meningitis related to AIDS. In these studies, most participants did not experience major side effects, indicating it was generally well tolerated. Although detailed safety information for its use in treating candidemia (a fungal blood infection) is limited, its safe use in other conditions is encouraging.

As this trial is in the early stages, researchers are closely monitoring the treatment's safety. However, previous research on Interferon Gamma-1B provides some confidence about its potential safety for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Candida blood infection?

Researchers are excited about Interferon Gamma-1B for treating Candida blood infections because it represents a novel approach compared to standard antifungal therapies. While typical treatments focus on directly attacking the fungus, Interferon Gamma-1B works by boosting the body's immune response to fight off the infection more effectively. This unique mechanism could provide a much-needed alternative for patients who do not respond well to current antifungal medications, potentially enhancing recovery rates and reducing the severity of infections.

What evidence suggests that Interferon Gamma-1B might be an effective treatment for Candida blood infection?

Research has shown that Interferon Gamma-1B can help the immune system fight fungal infections like Candida by activating immune cells that combat the infection. In this trial, some participants will receive Interferon Gamma-1B combined with standard antifungal therapy. Previous studies indicated that patients who received Interferon Gamma-1B had slightly better survival rates than those who did not, although the difference wasn't statistically significant. While it might not completely cure the infection on its own, Interferon Gamma-1B could be a useful addition to standard antifungal treatments. ^{1 4 5 6 7}

Who Is on the Research Team?

Frank vd Veerdonk, Dr.

Principal Investigator

Radboud University Medical Center

Are You a Good Fit for This Trial?

Adults with a recent Candida blood infection confirmed by a positive culture, showing signs of infection like fever or low blood pressure, and not severely ill to survive less than 24 hours. They must consent to the study (or have a legal representative do so) and agree to use contraception if applicable. Excluded are those with severe liver failure, history of seizures, recent immunological treatments, pregnant or lactating women, failed prior antifungal therapy for this infection.

Inclusion Criteria

Subjects with at least one positive blood culture isolation of Candida species from a specimen drawn within 120 hours prior to study entry

I agree to use contraception during the study and, if I'm a woman of childbearing age, I have a negative pregnancy test.

Subjects with clinical evidence of infection within 120 hours prior to enrollment, 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 vasopressor therapy, Signs of inflammation (swelling, heat, erythema, purulent drainage) from a site infected with Candida (e.g. joint, skin, eye, bone, esophagus), Radiologic findings of invasive candidiasis, Subject or their legal representative must sign a written informed consent form

Exclusion Criteria

I am currently pregnant or breastfeeding.

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

I have a documented history of epileptic seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rIFN-y immunotherapy, subcutaneous dose of 100 microgram thrice weekly for two weeks or until hospital discharge, in addition to standard of care

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Interferon Gamma-1B

Trial Overview The trial is testing Interferon Gamma-1B's safety and effectiveness in treating patients with candidemia. It's an open-label phase 2 study where all participants know they're receiving the treatment as researchers observe outcomes.

How Is the Trial Designed?

Group I: Interferon-Gamma Active Control 1 Intervention

Recombinant Interferon-Gamma 1b combined with standard therapy

Group II: Standard of care Active Control 1 Intervention

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

Interferon Gamma-1B is already approved in United States for the following indications:

Approved in United States as Actimmune for:

• Chronic granulomatous disease
• Severe, malignant osteopetrosis

Who Is Running the Clinical Trial?

Radboud University

Lead Sponsor

Trials

729

Recruited

298,000+

Radboud University Medical Center

Lead Sponsor

Trials

1,203

Recruited

1,157,000+

Horizon 2020 - European Commission

Collaborator

Trials

35

Recruited

14,200+

Published Research Related to This Trial

A single injection of a monoclonal antibody targeting gamma interferon, when given with a live Candida albicans vaccine, led to a nonprotective Th2 immune response instead of the desired protective Th1 response.

This treatment also changed the early expression levels of interleukin 4 and gamma interferon mRNA in CD4+ cells, indicating a significant alteration in the immune response mechanism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma interferon modifies CD4+ subset expression in murine candidiasis. Romani, L., Cenci, E., Mencacci, A., et al.[2021]

In a phase 2 study involving 75 patients with acute cryptococcal meningitis, adjuvant treatment with recombinant interferon-gamma 1b showed a significant increase in the rate of cerebrospinal fluid culture conversion compared to placebo, with 36% conversion in the 100 microg group and 32% in the 200 microg group versus 13% in the placebo group.

The treatment was well tolerated with no adverse effects on CD4 cell counts or HIV load, suggesting that rIFN-gamma 1b could be a safe and effective adjunct therapy for cryptococcal meningitis, meriting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant interferon- gamma 1b as adjunctive therapy for AIDS-related acute cryptococcal meningitis. Pappas, PG., Bustamante, B., Ticona, E., et al.[2022]

Recombinant rat interferon-gamma (rIFN-gamma) significantly reduces the growth of Candida albicans in the kidneys, spleen, and liver of mice when administered around the time of infection, demonstrating its protective efficacy.

The mechanism of action involves enhancing the ability of immune cells, specifically polymorphonuclear leukocytes, to kill C. albicans, thereby increasing host resistance to the infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant interferon-gamma enhances resistance to acute disseminated Candida albicans infection in mice. Kullberg, BJ., van 't Wout, JW., Hoogstraten, C., et al.[2021]

In a randomized controlled trial involving patients with HIV-associated cryptococcal meningitis, the addition of interferon-gamma (IFNγ) to standard therapy significantly increased the rate of fungal clearance from the cerebrospinal fluid, indicating enhanced treatment efficacy.

Both two doses and six doses of IFNγ were equally effective in improving clearance rates, and the treatment was well tolerated with no increase in adverse events, suggesting a safe addition to standard therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive interferon-γ immunotherapy for the treatment of HIV-associated cryptococcal meningitis: a randomized controlled trial. Jarvis, JN., Meintjes, G., Rebe, K., et al.[2023]

Cytokines, such as Interleukin-1 and interferon-gamma, show promise as adjunctive therapies to enhance host resistance against invasive fungal infections, particularly in immunocompromised patients.

Interferon-gamma has been effective in boosting the immune response against fungal infections like candidiasis in animal models, primarily by activating neutrophils, although its effectiveness is limited in patients with severe granulocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokines in the treatment of fungal infections. Kullberg, BJ., van 't Wout, JW.[2019]

Recombinant human interferon-gamma (rIFN-gamma) enhances the candidacidal activity of human granulocytes, leading to increased intracellular killing of Candida albicans and higher production of hydrogen peroxide (H2O2).

The study indicates that the enhanced killing ability of granulocytes stimulated by rIFN-gamma is primarily due to increased production of reactive oxygen radicals, suggesting a potential mechanism for improving immune response against Candida infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon-gamma activates the oxidative killing of Candida albicans by human granulocytes. Stevenhagen, A., van Furth, R.[2019]

Interferon-gamma (IFN-gamma) is crucial for the immune response against invasive candidiasis, a serious infection caused by the fungus Candida albicans, especially in immunocompromised individuals.

IFN-gamma enhances the activation of immune cells like phagocytes and promotes a protective Th1 response, which is essential for controlling the infection and generating effective antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IFN-gamma in Candida albicans infections. Gozalbo, D., Gil, ML.[2022]

Interferon-gamma (IFN-gamma) is crucial for the immune response against invasive candidiasis, produced by various immune cells in response to cytokines like IL-12 and IL-18.

IFN-gamma enhances the activation of phagocytes, supports antibody production, and promotes a protective Th1 immune response, highlighting its importance in controlling Candida albicans infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of IFN-gamma in immune responses to Candida albicans infections. Gozalbo, D., Maneu, V., Gil, ML.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04979052

NCT04979052 | Safety and Efficacy of Interferon-Gamma ... A multi-center open label adaptive randomized interventional phase 2 study to evaluate safety and efficacy of rIFN-y treatment in patiens with candidemia.

2. withpower.com withpower.com/trial/phase-3-candidemia-11-2021-95b70

Interferon Gamma-1B for Candida Blood Infection Research shows that Interferon Gamma-1B can enhance the body's immune response against fungal infections like Candida by activating certain immune cells. In ...

3. clinconnect.io clinconnect.io/trials/NCT04979052

Safety and Efficacy of Interferon-Gamma 1b in Patients This study aims to find better treatment options for patients experiencing candidemia, which can be life-threatening if not treated effectively. Gender. ALL.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6574079/

Clinical Use of Interferon-γ - PMC - PubMed Central Three-year survival in the IFN-γ arm was 28% compared to 18% in the placebo group, although this difference was not statistically significant. IFN-γ1b treatment ...

5. humanforschung-schweiz.ch humanforschung-schweiz.ch/en/trial-search/study-detail/62263/translate/en/?cHash=96ff03eed7648cf599fb12abe2e8fb5c

Safety and efficacy of recombinant Gamma interferon for ... Despite their effectiveness, these treatments do not always succeed in curing the infection or preventing complications, such as the dissemination of the fungus ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04979052/safety-and-efficacy-of-interferon-gamma-1b-in-patients-with-candidemia

Safety and Efficacy of Interferon-Gamma 1b in Patients ... A multi-center open label adaptive randomized interventional phase 2 study to evaluate safety and efficacy of rIFN-y treatment in patiens with candidemia.

7. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-recombinant-human-interferon-gamma-1b-with-standard-therapy-for-patients-with-candidemia/

Study of Recombinant Interferon-Gamma 1b Combined ... This clinical trial evaluates the safety and effectiveness of recombinant human interferon gamma 1b as an additional treatment for candidemia, a bloodstream ...