Olorofim Aspergillus Infection Study (OASIS)

Phase III, Adjudicator-blinded, Randomised Study to Evaluate Efficacy and Safety of Treatment With Olorofim Versus Treatment With AmBisome® Followed by Standard of Care in Patients With Invasive Fungal Disease Caused by Aspergillus Species

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 caused by proven IA or probable lower respiratory tract disease Aspergillus species (invasive aspergillosis, IA).

Study Overview

• Status: Active, not recruiting
• Conditions: Invasive Aspergillosis
• Intervention / Treatment: Drug: Olorofim; Drug: AmBisome®

Detailed Description

The mortality rate in immunosuppressed patients with IA is high even with effective modern antifungal drug treatment. Intrinsic and acquired resistance to azoles and amphotericin B, the two most effective classes of treatment, have been identified in Aspergillus species and are linked to this increased mortality.

Currently marketed antifungal drugs have limitations including limited dosage forms, DDIs, and significant adverse reactions.

For patients with IA who do not respond to or cannot tolerate a triazole therapy, treatment options are even more limited.

Olorofim is an antifungal candidate with a novel mechanism of action offering activity against resistant organisms, differences in safety profile, along with oral dosing, predictable and reliable pharmacokinetic (PK) profile and limited potential for DDIs.

The present study is designed to compare the efficacy, safety, and tolerability of olorofim with that of AmBisome® followed by guideline-based hierarchy standard of care (SOC) in patients with IA whose infection is either refractory to or unsuitable for azole therapy.

• Study Type: Interventional
• Enrollment (Estimated): 225
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Saint Leonards, New South Wales, Australia, 2065
      • Royal Northshore Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane & Women's Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3181
      • The Alfred Hospital
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Belgium
  • Bruges, Belgium, 8000
    • AZ Sint-Jan
  • Brussels, Belgium, 1070
    • Hôpital Erasme
  • Ghent, Belgium, 3000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
• Brazil
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-221
      • Santa Casa de Misericórdia de Belo Horizonte
    • Belo Horizonte, Minas Gerais, Brazil, 30110-934
      • Hospital Felicio Rocho
    • Passos, Minas Gerais, Brazil, 37904-020
      • Santa Casa de Misericordia de Passos
  • Paraná
    • Curitiba, Paraná, Brazil, 81520-060
      • Hospital Erasto Gaertner - Liga Paranaense de Combate Ao Cancer
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital de Clínicas de Porto Alegre
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital Sao Lucas Da Pucrs
    • Porto Alegre, Rio Grande do Sul, Brazil, 90020-090
      • Irmandade da Santa Casa de Misericordia de Porto Alegre
    • Santa Maria, Rio Grande do Sul, Brazil, 97105-900
      • Hospital da Universidade Federal de Santa Maria CEP/UFSM
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences - Juravinski Site
    • Toronto, Ontario, Canada, M5G1M1
      • Toronto General Hospital
    • Toronto, Ontario, Canada, M5G1N8
      • University Health Network
• China
  • Beijing, China, 100191
    • Peking University Third Hospital
  • Beijing, China, 100033
    • Peking University People's Hospital
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Changsha, China, 410000
    • Xiangya Hospital, Central South University
  • Chenzhou, China, 423000
    • Chenzhou No.1 people's Hospital
  • Fuzhou, China, 350001
    • Fujian Medical University Union Hospital
  • Guangzhou, China, 510080
    • Guangdong Provincial People's Hospital
  • Guangzhou, China, 510080
    • The First Affiliated Hospital of Sun Yat-sen University
  • Guangzhou, China, 510515
    • Nanfang Hospital of Southern Medical University
  • Hangzhou, China, 310003
    • The First Affiliated Hospital of Zhejiang University School of Medicine
  • Hefei, China, 230001
    • Anhui Provincial Hospital
  • Nanning, China, 530000
    • The People's Hospital of Guangxi Zhuang Autonomous Region
  • Shengyang, China, 110055
    • Shengjing Hospital of China Medical University
  • Shijiazhuang, China, 50004
    • The Second Hospital of Hebei Medical University
  • Xi'an, China, 710126
    • Xi'an International Medical Center
  • Zhengzhou, China, 450003
    • Henan Provincial People's Hospital
  • Anhui
    • Bengbu, Anhui, China, 233004
      • The First Affiliated Hospital of Bengbu Medical College
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Huazhong University of Science and Technology
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200040
      • Huashan Hospital Fudan University
  • Tianjin Municipality
    • Xiaobailou, Tianjin Municipality, China, 300020
      • Institute of Hematology and Blood Diseases Hospital
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • The 1st Affiliated Hosp of Wenzhou Medical University
• France
  • Bas Rhin
    • Strasbourg, Bas Rhin, France, 67200
      • Institut de Cancérologie de Strasbourg Europe - ICANS
  • Doubs
    • Besançon, Doubs, France, 25030
      • CHU Besancon - Hôpital Jean Minjoz
    • Besançon, Doubs, France, 25030
      • CHU de Besancon
  • Gironde
    • Bordeaux, Gironde, France, 33000
      • CHU Bordeaux Hopital Saint André
  • Haute Garonne
    • Toulouse, Haute Garonne, France, 31059
      • Institut Universitaire Du Cancer de Toulouse- Iuct-O
  • Ille-et-Vilaine
    • Rennes, Ille-et-Vilaine, France, 35000
      • CHU de Rennes - Hôpital Pontchaillou
  • Loire Atlantique
    • Nantes, Loire Atlantique, France, 44093
      • CHU de Nantes CIC Hematologie
  • Nord
    • Lille, Nord, France, 59037
      • Hospital Claude Huriez
  • Paris
    • Paris, Paris, France, 75015
      • Hôpital Necker - Enfants Malades
• Germany
  • Berlin, Germany, 12203
    • Charité Universitätsmedizin Berlin
  • Cologne, Germany, 59037
    • Universitaetsklinikum Koeln
  • Hamburg-Eppendorf, Germany, 30625
    • UKE Universitaetsklinikum-Hamburg Eppendorf
  • Saxony
    • Leipzig, Saxony, Germany, 4103
      • Universitätsklinikum Leipzig
• Israel
  • Beersheba, Israel, 84001
    • Soroka University Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital - Ein Kerem
  • Ramat Gan, Israel, 5265601
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center Pt
• Italy
  • Genova, Italy, 16132
    • IRCCS Ospedale Policlinico San Martino
  • Milan, Italy, 20132
    • Ospedale San Raffaele
  • Milan, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Modena, Italy, 41124
    • AOU Policlinico di Modena
  • Perugia, Italy, 6129
    • Clinica Malattie Infettive Dipartimento di Medicina e Chirurgia dell'Università
  • Pisa, Italy, 56100
    • Azienda Ospedaliero Universitaria Pisana (Presidio di Cisanello)
  • Roma, Italy, 168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Roma, Italy, 149
    • INMI Lazzaro Spallanzani IRCCS
  • Campania
    • Napoli, Campania, Italy, 80138
      • Azienda Ospedaliera Universitaria Luigi Vanvitelli
  • Di Monza E Della Brianza
    • Monza, Di Monza E Della Brianza, Italy, 20900
      • Fondazione IRCCS San Gerardo dei Tintori
  • Milano
    • Rozzano, Milano, Italy, 2089
      • Istituto Clinico Humanitas
• Japan
  • Bunkyō City, Japan, 1138677
    • Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
  • Nagasaki, Japan, 852 8501
    • Nagasaki University Hospital
  • Okayama, Japan, 700 8558
    • Okayama University Hospital
  • Saitama, Japan, 3290431
    • Saitama Medical Center Jichi Medical University
  • Shimotsuke, Japan, 3290431
    • Jichi Medical University Hospital
  • Chiba
    • Chiba, Chiba, Japan, 260 8677
      • Chiba University Hospital
  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 812 8582
      • Kyushu University Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 980 8574
      • Tohoku University Hospital
  • Osaka
    • Osaka, Osaka, Japan, 541 8567
      • Osaka International Cancer Institute
    • Osaka, Osaka, Japan, 545 8586
      • Osaka Metropolitan University Hospital
    • Ōsaka-sayama, Osaka, Japan, 589 8511
      • Kindai University Hospital
  • Tokyo
    • Minato-Ku, Tokyo, Japan, 105-8471
      • The Jikei University Hospital
  • Tokyo to
    • Minatoku, Tokyo to, Japan, 105 8470
      • Toranomon Hospital
• Netherlands
  • Nijmegen, Netherlands, 6525GA
    • Radboud Nijmegen
  • Utrecht, Netherlands, 3508 GA
    • UMC Utrecht
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
  • Wellington Region
    • Newtown, Wellington Region, New Zealand, 6021
      • Wellington Regional Hospital
• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital- Parent
  • Singapore, Singapore, 117599
    • National University Hospital
• South Korea
  • Seoul
    • Bucheon-si, Seoul, South Korea, 06591
      • The Catholic University of Korea
    • Irwon-dong, Seoul, South Korea, 06351
      • Samsung Medical Center
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 8036
    • Hospital Clinic De Barcelona
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Madrid
    • Retiro, Madrid, Spain, 28007
      • Hospital General Universitario Gregorio Marañon
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • New Taipei City, Taiwan, 23561
    • Taipei Medical University - Shuang Ho Hospital, Ministry of Health and Welfare
  • Taichung, Taiwan, 404
    • China Medical University Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
• Thailand
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital
  • Bangkok
    • Bangkok Noi, Bangkok, Thailand, 10700
      • Siriraj Hospital
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06100
    • Hacettepe University Medical Faculty
  • Ankara, Turkey (Türkiye), 06800
    • Ankara City Hospital
  • Diyarbakır, Turkey (Türkiye), 21280
    • Dicle University, Medical Faculty
  • Istanbul, Turkey (Türkiye), 34303
    • Acibadem Atakent Hospital
  • Izmir, Turkey (Türkiye), 35100
    • Ege University Medical Faculty
  • Samsun, Turkey (Türkiye), 55270
    • Ondokuz Mayis Univ. Med. Fac.
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • London, United Kingdom, W6 8RP
    • Imperial College London
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4XW
      • University Hospital of Wales
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Health System
    • San Francisco, California, United States, 94143
      • UCSF Helen Diller Medical Center at Parnassus Heights
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 64111
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins Hospital
    • Bethesda, Maryland, United States, 20892
      • NIH Clinical Center ,NIAID,NIH
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Clairvoyant Research Group, LLC
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers RWJMS
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine NY Presbyterian Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke Department of Medicine Infectious Diseases Division
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Health OU Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center Health System
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist
  • Washington
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and female patients ages over 18 years and weighing more than 30 kg
2. Patients with proven IA at any site or probable LRTD IA per EORTC/MSG 2019 criteria as adapted for this study and where the duration of specific therapy for this episode of IA has been ≤ 28 days. For purposes of this inclusion, the duration of specific therapy includes any mould-active therapy given for this episode of IA whether subsequently judged potentially effective or not.
3. Patients requiring therapy with an antifungal agent other than a mould-active azole, and who have had ≤ 96 hours of potentially effective prior therapy. Potentially effective prior therapy includes any agent to which the infecting strain of Aspergillus is likely to be susceptible. There are no exclusions or limitations on such agents (eg, AmBisome® is permitted) other than their duration.
4. AmBisome® is an appropriate therapy for the patient.

Exclusion Criteria:

1. Women who are pregnant or breastfeeding.
2. Known history of allergy, hypersensitivity, or any serious reaction to any component of the study drug
3. Patients with only chronic aspergillosis, aspergilloma, or allergic bronchopulmonary aspergillosis.
4. Suspected mucormycosis (zygomycosis).
5. Patients with a known active second fungal infection of any type, other than candidiasis that can be treated with fluconazole.
6. The requirement for ongoing use of echinocandin as Candida prophylaxis.
7. Microbiological findings (eg, bacteriological, virological) or other potential conditions that are temporally related and suggest a different aetiology for the clinical features.
8. Human immunodeficiency virus (HIV) infection but not currently receiving antiretroviral therapy.
9. Patients with a baseline prolongation of QT using Fridericia's Correction Formula (QTcF) ≥ 500 msec, or at high risk for QT/QTc prolongation.
10. Evidence of hepatic dysfunction.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Olorofim; Olorofim versus AmBisome followed by Standard of Care (SOC)	Drug: Olorofim; Loading Dose: 5 tablets (150 mg) to be taken twice daily at a 12-hour (± 1 hour) interval on Day 1 Maintenance Dose: 3 tablets (90 mg) to be taken twice daily at 12-hour (± 1 hour) intervals from Day 2 until Day 84 (± 7 days); Other Names: Olorofim (F901318)
Active Comparator: AmBisome; Olorofim versus AmBisome followed by Standard of Care (SOC)	Drug: AmBisome®; Initial course of at least 10 days of AmBisome® administered daily at a dose of 3 mg/kg by IV infusion over a 30- to 60-minute period or according to local guidelines Administration of SOC will follow international, national, or local guidelines and product labelling.; Other Names: AmBisome® (liposomal amphotericin B)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	To compare all-cause mortality (ACM) at Day 42 following treatment with olorofim versus treatment with AmBisome® followed by standard of care (SOC) in the intent-to-treat (ITT) population of patients with Invasive Fungal Disease (IFD) caused by proven Invasive Aspergillosis (IA) at any site or probable lower respiratory tract disease (LRTD) Aspergillus species (invasive aspergillosis, IA).	Treatment Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Assessment	To monitor incidence of Adverse Events and Serious Adverse Events in both treatment arms (Olorofim or AmBisome followed by Standard of Care).	up to the Day 84 and 4-week Follow-up (FU)
Adjudicated Assessment of Overall outcome	To compare the effects of treatment with olorofim versus treatment with AmBisome® followed by SOC on Data Review Committee (DRC)-adjudicated assessment of overall outcome in patients with proven IA or probable LRTD IA at Day 42, Day 84, and End of Treatment.	Day 42, Day 84, and End of Treatment (anytime during the study between first administration and Day 84)
Investigator-assessed overall response	Investigator-assessed overall response (integrating clinical, radiological, and mycological response).	Day 14, Day 28, Day 42, Day 84, EOT (End of Treatment - Maximum Treatment 84 days [± 7 Days]), and 4-week Follow-up (FU).
To compare the effects of treatment with olorofim versus treatment with AmBisome® followed by SOC on Galactomannan index.	The Sponsor's expert advisors suggested that an appropriate rule would be a failure of the GM to decline from baseline. The experts also state that they have seen very significant variation on retesting of both BAL and serum GM samples and believe it is more appropriate to state a fixed reduction of ≥ 1.0 units than any percentage reduction. These rules are used for changes in GM that document failure of therapy: Serum: After 8 or more days of treatment, serum GM has neither (1) fallen by ≥ 1 unit nor (2) to < 0.5 based on measurements taken at least 8 days apart.; BAL: After 8 or more days of treatment, positive GM from BAL in a patient with a previous BAL test that did not meet the definition of positive (too low or entirely negative) without regard for the interval of time between samples.	Day 14, Day 28, Day 42, Day 84, EOT (End of Treatment - Maximum Treatment 84 days [± 7 Days]) and 4-week Follow-up (FU)
To collect additional olorofim and the disproportionate metabolite H26C pharmacokinetic (PK) data for inclusion in a Population PK model	To collect plasma concentration of olorofim and H26C metabolic for for PK analysis (pre-dose and intensive PK). No non-compartmental PK analysis will be performed on the data relating to pre-dose samples and intensive PK samples, apart from data collected from selected regions, which will be reported separately. All relevant olorofim data will be provided to support population PK modelling, which will be reported separately.	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])
Data Review Committee's Assessment of Patient Mortality	Study data will be independently assessed by a blinded DRC consisting of independent experts in the diagnosis and management of IA, providing an independent adjudication of each patient's mortality based on the survival status collect at time frame.	Day 42 and 84 and EOT (End of Treatment - Maximum Treatment 84 days [± 7 Days])
Diagnosis of a secondary fungal infection	To compare incidence of a secondary fungal infection when patients treated with olorofim versus treatment with AmBisome followed by SOC.	at any time through End Of Treatment
Quality of life as measured by the 5 Level 5 Dimension (EQ-5D-5L) at Baseline	To assess patient's quality of life measured by the 5-Level 5-Dimension EuroQol Group Health-related Quality of Life Questionnaire (EQ-5D-5L) in both treatment groups	Days 14 and EOT (End of Treatment - Maximum Treatment 84 days [± 7 Days])
Survival status	All-cause mortality will be assessed using survival status at time frame.	Day 42, Day 84, and End Of Treatment and at the 4 weeks ± 7 days FU

Collaborators and Investigators

• Sponsor: F2G Biotech GmbH
• Collaborators: IQVIA Pty Ltd; Shionogi
• Investigators: Principal Investigator: Johan Maertens, MD, UZ Leuven

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2022
• Primary Completion (Actual): November 18, 2025
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: September 7, 2021
• First Submitted That Met QC Criteria: October 19, 2021
• First Posted (Actual): November 1, 2021

Study Record Updates

• Last Update Posted (Estimated): January 6, 2026
• Last Update Submitted That Met QC Criteria: January 4, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Aspergillus species; Invasive fungal disease (IFD); Olorofim; Non-azole antifungal; Azole resistance
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Invasive Fungal Infections; Anti-Infective Agents; Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; liposomal amphotericin B; olorofim
• Other Study ID Numbers: F901318/0041

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No