What side effects are associated with this type of intervention?

Common treatments for Invasive Aspergillosis, such as voriconazole, isavuconazole, and amphotericin B, have several known side effects. Voriconazole can cause visual disturbances, liver enzyme abnormalities, and skin reactions. Isavuconazole may lead to gastrointestinal issues, liver enzyme elevations, and hypokalemia. Amphotericin B is associated with nephrotoxicity, infusion-related reactions, and electrolyte imbalances. While specific side effects of Olorofim are not detailed, it is important to monitor for potential adverse reactions similar to those seen with other antifungal agents.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Invasive Aspergillosis, including voriconazole, isavuconazonium sulfate, and liposomal amphotericin B. Voriconazole, a triazole antifungal, inhibits fungal cytochrome P450-dependent enzyme lanosterol 14-alpha-demethylase, disrupting cell membrane formation. Isavuconazonium sulfate, another triazole, also inhibits the same enzyme. Liposomal amphotericin B binds to ergosterol in the fungal cell membrane, creating pores that lead to cell death. While these drugs have different mechanisms compared to Olorofim, which inhibits dihydroorotate dehydrogenase, they are all part of the broader antifungal treatment landscape for IA.

What other types of research exist?

Promising novel alternatives to Olorofim for treating invasive aspergillosis include Rezafungin, a long-acting echinocandin with a unique pharmacokinetic profile, and Ibrexafungerp, a glucan synthase inhibitor with broad-spectrum antifungal activity. Both have shown efficacy in recent clinical trials and represent new classes of antifungal agents with potential benefits for patients with invasive aspergillosis.

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Liposomal Amphotericin B

Olorofim vs AmBisome® for Aspergillosis (OASIS Trial)

Phase 3

Recruiting

Led By Johan Maertens, MD

Research Sponsored by F2G Biotech GmbH

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients with proven invasive aspergillosis (IA) at any site or probable lower respiratory tract disease (LRTD) IA per EORTC/MSG 2019 criteria as adapted for this study

Be older than 18 years old

Must not have

Patients with a baseline prolongation of QT using Fridericia's Correction Formula (QTcF) ≥ 500 msec, or at high risk for QT/QTc prolongation

Human immunodeficiency virus (HIV) infection but not currently receiving antiretroviral therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day 14, day 28, day 42, day 84, eot (end of treatment - maximum treatment 84 days [± 7 days]), and 4-week follow-up (fu).

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing a new antifungal drug called olorofim against an existing treatment, AmBisome®, in patients with tough fungal infections. These patients have limited options because their infections resist current treatments or they can't tolerate them. Olorofim works differently from other drugs, can be taken orally, and has fewer interactions with other medications. AmBisome is a liposomal formulation of amphotericin B, known for its broad-spectrum antifungal activity and reduced toxicity compared to conventional amphotericin B.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include allergic reactions to medication components and liver issues. There may also be risks associated with infusion treatments such as discomfort at the injection site or systemic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with invasive aspergillosis.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I am HIV positive but not on antiretroviral therapy.

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I have liver problems.

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I am not pregnant or breastfeeding.

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I have a fungal infection that is not candidiasis but can be treated with fluconazole.

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I am suspected to have a fungal infection known as mucormycosis.

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I am using echinocandin for fungal infection prevention.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day 10, day 14, day 21, day 28, day 42, day 56, day 70, day 84, and at eot (end of treatment - maximum treatment 84 days [± 7 days])

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day 10, day 14, day 21, day 28, day 42, day 56, day 70, day 84, and at eot (end of treatment - maximum treatment 84 days [± 7 days])

This trial's timeline: 3 weeks for screening, Varies for treatment, and day 10, day 14, day 21, day 28, day 42, day 56, day 70, day 84, and at eot (end of treatment - maximum treatment 84 days [± 7 days]) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

All-cause mortality

Secondary study objectives

Adjudicated Assessment of Overall outcome

Data Review Committee's Assessment of Patient Mortality

Diagnosis of a secondary fungal infection

+6 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Active Control

Group I: OlorofimActive Control1 Intervention

Olorofim versus AmBisome followed by Standard of Care (SOC)

Group II: AmBisomeActive Control1 Intervention

Olorofim versus AmBisome followed by Standard of Care (SOC)

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Invasive Aspergillosis (IA) include antifungal agents such as voriconazole, amphotericin B, and the newer agent olorofim. Voriconazole works by inhibiting the enzyme 14-alpha-demethylase, crucial for ergosterol synthesis, thereby disrupting fungal cell membrane integrity. Amphotericin B binds to ergosterol in the fungal cell membrane, creating pores that lead to cell death. Olorofim, a novel agent, inhibits dihydroorotate dehydrogenase, disrupting pyrimidine biosynthesis, which is essential for fungal DNA and RNA synthesis. These mechanisms are vital for IA patients as they target critical fungal processes, reducing fungal load and improving patient outcomes.

In vitro activity of the novel antifungal olorofim against dermatophytes and opportunistic moulds including Penicillium and Talaromyces species.