Interferon Gamma-1B for Candida Blood Infection

(HDM-FUN Cand Trial)

Recruiting at 5 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

Trial Summary

What is the purpose of this trial?

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

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.

What evidence supports the effectiveness of the drug Interferon Gamma-1B for treating Candida blood infections?

Research shows that Interferon Gamma-1B can enhance the body's immune response against fungal infections like Candida by activating certain immune cells. In animal studies, it has been effective in fighting Candida infections, although its effectiveness may be limited in cases of severely weakened immune systems. ^{1 2 3 4 5}

Is Interferon Gamma-1B generally safe for human use?

Interferon Gamma-1B has been studied in humans for conditions like AIDS-related cryptococcal meningitis and was found to be well tolerated, meaning it did not cause significant side effects. This suggests it is generally safe for human use, although specific safety data for Candida blood infections is not available. ^{1 3 4 5 6}

How does the drug Interferon Gamma-1B work differently for Candida blood infection?

Interferon Gamma-1B is unique because it boosts the body's immune response by activating certain immune cells to better fight off Candida infections. Unlike standard antifungal drugs, it enhances the body's natural defenses, particularly by increasing the activity of cells that kill the fungus. ^{1 3 5 7 8}

Research Team

Frank vd Veerdonk, Dr.

Principal Investigator

Radboud University Medical Center

Eligibility Criteria

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.

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Cytokines in the treatment of fungal infections. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Adjunctive interferon-γ immunotherapy for the treatment of HIV-associated cryptococcal meningitis: a randomized controlled trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Gamma interferon modifies CD4+ subset expression in murine candidiasis. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Recombinant interferon- gamma 1b as adjunctive therapy for AIDS-related acute cryptococcal meningitis. [2022]

5. Singapore pubmed.ncbi.nlm.nih.gov

Role of IFN-gamma in immune responses to Candida albicans infections. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Recombinant interferon-gamma enhances resistance to acute disseminated Candida albicans infection in mice. [2021]

7. Singapore pubmed.ncbi.nlm.nih.gov

IFN-gamma in Candida albicans infections. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Interferon-gamma activates the oxidative killing of Candida albicans by human granulocytes. [2019]