Olorofim vs AmBisome® for Aspergillosis

(OASIS Trial)

Recruiting at 167 trial locations

Overseen By Gautam Kalyatanda

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: F2G Biotech GmbH

Must be taking: Antifungals

Must not be taking: Echinocandins

Disqualifiers: Pregnancy, HIV without ART, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

225 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare two treatments for invasive aspergillosis (IA), a serious lung infection caused by Aspergillus species: olorofim, a new potential drug, and AmBisome®, an antifungal medication. The researchers seek to determine which treatment more effectively manages this condition. The trial seeks participants with a confirmed case of IA who require antifungal therapy and have not received more than 28 days of specific treatment for this infection. Participants should not have chronic forms of aspergillosis or other fungal infections. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a new treatment option.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on a mould-active azole, you may need to switch to a different antifungal agent.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that olorofim is promising in terms of safety. It kills fungi by disrupting a key process they need to survive. Previous studies found that olorofim is generally well-tolerated by patients with serious fungal infections, such as aspergillosis. Few reports of serious side effects exist, making it a potential option for those with limited treatment choices.

AmBisome has already received FDA approval for treating fungal infections. It is usually well-tolerated, though some patients might experience side effects like fever, chills, or kidney issues. Since AmBisome is widely used, its safety profile is well-known.

This trial compares both treatments to evaluate their effectiveness against each other. Understanding the safety of each can help determine if joining the trial is a suitable option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for aspergillosis?

Researchers are excited about Olorofim because it offers a novel approach to treating aspergillosis, a serious fungal infection. Unlike conventional treatments like AmBisome®, which work by binding to the fungal cell membrane, Olorofim targets a different part of the fungal cell machinery, inhibiting an enzyme essential for the fungus's survival. This unique mechanism of action could potentially offer an alternative for patients who don't respond well to existing therapies. Additionally, Olorofim is being investigated for its potential to be effective against a broader range of fungal species, which could make it a versatile option in the fight against difficult-to-treat infections.

What evidence suggests that this trial's treatments could be effective for aspergillosis?

Research shows that olorofim, one of the treatments studied in this trial, effectively targets Aspergillus species, fungi responsible for invasive aspergillosis (IA). Studies have found that olorofim can treat IA even when other treatments prove ineffective. It has succeeded in lab tests and in patients, offering hope for those with challenging fungal infections. AmBisome®, the other treatment option in this trial, is a well-known and effective treatment for managing IA. Both treatments offer benefits, but olorofim might provide a new option for those with resistant strains. ^{1 2 3 5 6}

Who Is on the Research Team?

Johan MAERTENS

Principal Investigator

UZ Leuven

Are You a Good Fit for This Trial?

Adults over 18 years old, weighing more than 40 kg with proven or probable invasive aspergillosis (IA) who need non-azole antifungal therapy due to azole resistance, infection despite azole use, or potential drug interactions. Not for pregnant/breastfeeding women, those with chronic aspergillosis forms, other active fungal infections except certain candidiasis cases, hepatic dysfunction, known allergies to study drugs, suspected mucormycosis, echinocandin-treated Candida prophylaxis patients or untreated HIV.

Inclusion Criteria

I have been diagnosed with invasive aspergillosis.

I am over 18 years old and weigh more than 40 kg.

I need a different antifungal treatment because the usual one doesn't work for me.

Exclusion Criteria

You have had a serious allergic reaction or bad side effects from any part of the study drug.

My heart's electrical cycle is longer than normal or I'm at high risk for it.

I am HIV positive but not on antiretroviral therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either olorofim or AmBisome followed by standard of care for up to 84 days

12 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Follow-up visit at 4 weeks post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• AmBisome®
• Olorofim

Trial Overview The trial is testing the effectiveness of a new antifungal treatment called Olorofim compared to AmBisome® followed by standard care in patients with invasive Aspergillus infections. It aims to see if Olorofim can be a better option for those who cannot take mould-active azoles.

How Is the Trial Designed?

Group I: Olorofim Active Control 1 Intervention

Olorofim versus AmBisome followed by Standard of Care (SOC)

Group II: AmBisome Active Control 1 Intervention

Olorofim versus AmBisome followed by Standard of Care (SOC)

AmBisome® is already approved in United States, Canada, Japan, European Union for the following indications:

Approved in United States as AmBisome for:

• Systemic or disseminated infections due to Candida, Aspergillus, or Cryptococcus
• Empirical therapy for presumed fungal infections in febrile, neutropenic patients
• Visceral leishmaniasis

Approved in Canada as AmBisome for:

• Systemic or disseminated infections due to Candida, Aspergillus, or Cryptococcus in patients who are refractory to or intolerant of conventional amphotericin B therapy, or have renal impairment

Approved in Japan as AmBisome for:

• Systemic mycosis, respiratory mycosis, fungal meningitis, and disseminated visceral mycosis caused by Aspergillus species, Candida species or Cryptococcus species
• Visceral leishmaniasis

Approved in European Union as AmBisome for:

• Systemic or disseminated infections due to Candida, Aspergillus, or Cryptococcus
• Visceral leishmaniasis

Who Is Running the Clinical Trial?

F2G Biotech GmbH

Lead Sponsor

Trials

21

Recruited

1,800+

Shionogi

Industry Sponsor

Trials

122

Recruited

42,100+

Dr. Isao Teshirogi

Shionogi

Chief Executive Officer since 2008

PhD in Pharmaceutical Sciences from the University of Tokyo

Dr. Takuko Sawada

Shionogi

Chief Medical Officer since 2022

MD from a recognized institution (specific details not found)

Iqvia Pty Ltd

Industry Sponsor

Trials

120

Recruited

177,000+

Ari Bousbib

Iqvia Pty Ltd

Chief Executive Officer since 2016

MBA from Columbia University, Master of Science in Mathematics and Mechanical Engineering from Ecole Superieure des Travaux Publics, Paris

Jeffrey Spaeder

Iqvia Pty Ltd

Chief Medical Officer

MD

Published Research Related to This Trial

AmBisome, a formulation of amphotericin B, has been shown to be safe and effective in both therapeutic and prophylactic settings for adult and pediatric patients undergoing transplantation, significantly reducing fungal colonization and invasive Candida infections compared to placebo.

In a study involving 14 children undergoing bone marrow transplantation, AmBisome eradicated invasive fungal infections in 86% of cases, with minimal treatment withdrawals due to side effects, despite its higher cost compared to conventional amphotericin B.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten years' experience with liposomal amphotericin B in transplant recipients at Huddinge University Hospital. Ringdén, O.[2019]

All formulations of amphotericin B tested, including Fungizone, AmBisome, Amphocil, and Abelcet, were effective in prolonging survival in mice with systemic aspergillosis, with AmBisome showing results nearly equivalent to Fungizone.

No lipid-based formulation consistently outperformed Fungizone, and while all treatments showed efficacy, none resulted in complete cures in both kidneys and brain, indicating a need for further research on optimal treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacies of four amphotericin B formulations--Fungizone, amphotec (Amphocil), AmBisome, and Abelcet--against systemic murine aspergillosis. Clemons, KV., Stevens, DA.[2021]

In a rat model of pulmonary aspergillosis, AmBisome (10 mg/kg) was more effective than Fungizone (1 mg/kg) in reducing fungal growth and improving survival rates after infection with Aspergillus fumigatus.

AmBisome not only reduced the spread of infection from the left lung to the right lung but also completely prevented liver and spleen complications at the higher dosage, suggesting its potential for use in prophylactic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal amphotericin B (AmBisome) reduces dissemination of infection as compared with amphotericin B deoxycholate (Fungizone) in a rate model of pulmonary aspergillosis. Leenders, AC., de Marie, S., ten Kate, MT., et al.[2019]

In a study involving mice with pulmonary aspergillosis, AmBisome significantly improved survival rates and reduced fungal burden compared to Fungizone, especially at higher doses (10 mg/kg).

AmBisome was found to localize effectively at the infection site in the lungs, which likely contributes to its superior efficacy in treating this type of fungal infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study on the efficacy of AmBisome and Fungizone in a mouse model of pulmonary aspergillosis. Takemoto, K., Yamamoto, Y., Ueda, Y., et al.[2013]

AmBisome, a liposomal formulation of amphotericin B, demonstrated high prophylactic efficacy against fungal infections in both immunocompetent and immunosuppressed mice, with all treated mice surviving after exposure to Histoplasma capsulatum and significant reductions in fungal burden.

In comparison to the conventional amphotericin B (Fungizone), AmBisome showed lower kidney fungal burdens and improved survival rates, indicating its potential as a safer and more effective antifungal treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose AmBisome (Liposomal amphotericin B) as prophylaxis for murine systemic candidiasis and histoplasmosis. Garcia, A., Adler-Moore, JP., Proffitt, RT.[2021]

In a study using immunocompromised mice, aerosolized AmBisome (liposomal amphotericin B) demonstrated superior prophylactic efficacy against pulmonary aspergillosis compared to Fungizone (non-liposomal amphotericin B), particularly at medium levels of Aspergillus fumigatus exposure.

AmBisome not only cleared 80% of the fungal load in the lungs at a medium challenge level but also showed significantly higher lung drug retention, while both formulations were safe with no elevated kidney function markers in treated animals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic efficacy of aerosolized liposomal (AmBisome) and non-liposomal (Fungizone) amphotericin B in murine pulmonary aspergillosis. Allen, SD., Sorensen, KN., Nejdl, MJ., et al.[2022]

Inadvertent administration of amphotericin B instead of liposomal amphotericin has led to patient harm, highlighting the critical need for healthcare practitioners to be aware of the differences between these two formulations.

The similarity in packaging and dosing recommendations between AmBisome and Fungizone increases the risk of medication errors, suggesting that both organizational strategies and product design improvements are necessary to enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Problem with Amphotericin. Cavell, G.[2020]

AmBisome, a liposomal formulation of amphotericin B, is effective for treating severe fungal infections in febrile neutropenic patients and those resistant to standard amphotericin B, demonstrating a unique pharmacokinetic profile with increased plasma concentration and lower clearance.

The mechanism of action involves AmBisome accumulating at fungal infection sites, where it disrupts its liposomal structure upon binding to the fungal cell wall, allowing amphotericin B to bind to ergosterol in the fungal membrane, leading to cell lysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AmBisome (liposomal amphotericin B): a comparative review. Boswell, GW., Buell, D., Bekersky, I.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12486828/

Cost-effectiveness of olorofim in the treatment of invasive ... This study aimed to estimate the cost-effectiveness of treating invasive aspergillosis (IA) in patients with limited treatment options with ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1473309925002245

Olorofim for the treatment of invasive fungal diseases in ... Olorofim is dosed orally, has 68% bioavailability following first-pass effect clearance, and shows linear systemic exposure.24. Here, we report ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6535528/

Efficacy of Olorofim (F901318) against Aspergillus fumigatus ... These results show olorofim to be a promising therapeutic agent for invasive aspergillosis. ... In conclusion, our data provide additional promising results which ...

4. bmcinfectdis.biomedcentral.com bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-10143-3

Review of the novel antifungal drug olorofim (F901318) Olorofim shows good in vitro and in vivo activity against Aspergillus species, rare and difficult to treat moulds and endemic dimorphic fungi, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05101187

NCT05101187 | Olorofim Aspergillus Infection Study The purpose of this study is to compare treatment with olorofim versus treatment with AmBisome® followed by standard of care (SOC) in patients with IFD ...

6. thelancet.com thelancet.com/journals/laninf/article/PIIS1473-3099(25)00224-5/abstract

Olorofim for the treatment of invasive fungal diseases in ... It impairs fungal pyrimidine biosynthesis, leading to cell death. We sought initial data on the efficacy and safety of olorofim as a therapy for ...