Olorofim Aspergillus Infection Study
- Registration Number
- NCT05101187
- Lead Sponsor
- F2G Biotech GmbH
- Brief Summary
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).
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 225
- Male and female patients ages over 18 years and weighing more than 30 kg
- 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.
- 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.
- AmBisome® is an appropriate therapy for the patient.
- Women who are pregnant or breastfeeding.
- Known history of allergy, hypersensitivity, or any serious reaction to any component of the study drug
- Patients with only chronic aspergillosis, aspergilloma, or allergic bronchopulmonary aspergillosis.
- Suspected mucormycosis (zygomycosis).
- Patients with a known active second fungal infection of any type, other than candidiasis that can be treated with fluconazole.
- The requirement for ongoing use of echinocandin as Candida prophylaxis.
- Microbiological findings (eg, bacteriological, virological) or other potential conditions that are temporally related and suggest a different aetiology for the clinical features.
- Human immunodeficiency virus (HIV) infection but not currently receiving antiretroviral therapy.
- Patients with a baseline prolongation of QT using Fridericia's Correction Formula (QTcF) ≥ 500 msec, or at high risk for QT/QTc prolongation.
- Evidence of hepatic dysfunction.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AmBisome AmBisome® Olorofim versus AmBisome followed by Standard of Care (SOC) Olorofim Olorofim Olorofim versus AmBisome followed by Standard of Care (SOC)
- Primary Outcome Measures
Name Time Method All-cause mortality Treatment Day 42 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).
- Secondary Outcome Measures
Name Time Method Data Review Committee's Assessment of Patient Mortality Day 42 and 84 and EOT (End of Treatment - Maximum Treatment 84 days [± 7 Days]) 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.
Quality of life as measured by the 5 Level 5 Dimension (EQ-5D-5L) at Baseline Days 14 and EOT (End of Treatment - Maximum Treatment 84 days [± 7 Days]) 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
Investigator-assessed overall 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). Investigator-assessed overall response (integrating clinical, radiological, and mycological response).
Survival status Day 42, Day 84, and End Of Treatment and at the 4 weeks ± 7 days FU All-cause mortality will be assessed using survival status at time frame.
Adjudicated Assessment of Overall outcome Day 42, Day 84, and End of Treatment (anytime during the study between first administration and Day 84) 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.
To compare the effects of treatment with olorofim versus treatment with AmBisome® followed by SOC on Galactomannan index. Day 14, Day 28, Day 42, Day 84, EOT (End of Treatment - Maximum Treatment 84 days [± 7 Days]) and 4-week Follow-up (FU) 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:
1. 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.
2. 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.To collect additional olorofim and the disproportionate metabolite H26C pharmacokinetic (PK) data for inclusion in a Population PK model 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]) 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.
Diagnosis of a secondary fungal infection at any time through End Of Treatment To compare incidence of a secondary fungal infection when patients treated with olorofim versus treatment with AmBisome followed by SOC.
Safety Assessment up to the Day 84 and 4-week Follow-up (FU) To monitor incidence of Adverse Events and Serious Adverse Events in both treatment arms (Olorofim or AmBisome followed by Standard of Care).
Trial Locations
- Locations (140)
Hôpital Erasme
🇧🇪Bruxelles, Belgium
Hospital Claude Huriez
🇫🇷Lille, Nord, France
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
University Health Network
🇨🇦Toronto, Ontario, Canada
Institut Universitaire du Cancer de Toulouse- IUCT-O
🇫🇷Toulouse, Haute Garonne, France
UKE Universitaetsklinikum-Hamburg Eppendorf
🇩🇪Hamburg-Eppendorf, Germany
Istituto Clinico Humanitas
🇮🇹Rozzano, Milano, Italy
University Hospital of Wales
🇬🇧Cardiff, Wales, United Kingdom
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
University of California Davis Health System
🇺🇸Sacramento, California, United States
UCSF Helen Diller Medical Center at Parnassus Heights
🇺🇸San Francisco, California, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Augusta University
🇺🇸Augusta, Georgia, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
The Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
NIH Clinical Center ,NIAID,NIH
🇺🇸Bethesda, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Clairvoyant Research Group, LLC
🇺🇸Las Vegas, Nevada, United States
Rutgers RWJMS
🇺🇸New Brunswick, New Jersey, United States
Weill Cornell Medicine NY Presbyterian Hospital
🇺🇸New York, New York, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Duke Department of Medicine Infectious Diseases Division
🇺🇸Durham, North Carolina, United States
OU Health OU Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
University of Pittsburgh Medical Center Health System
🇺🇸Pittsburgh, Pennsylvania, United States
Houston Methodist
🇺🇸Houston, Texas, United States
Royal NorthShore Hospital
🇦🇺Saint Leonards, New South Wales, Australia
Royal Brisbane & Women's Hospital
🇦🇺Herston, Queensland, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
AZ Sint-Jan
🇧🇪Brugge, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Hospital Felício Rocho
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Santa Casa de Misericórdia de Belo Horizonte
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Santa Casa de Misericórdia de Passos
🇧🇷Passos, Minas Gerais, Brazil
Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
🇧🇷Curitiba, Paraná, Brazil
Irmandade da Santa Casa de Misericórdia de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital de Clínicas de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Hospital São Lucas da PUCRS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital da Universidade Federal de Santa Maria CEP/UFSM
🇧🇷Santa Maria, Rio Grande Do Sul, Brazil
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Hamilton Health Sciences - Juravinski Site
🇨🇦Hamilton, Ontario, Canada
The First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, Anhui, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Qilu Hospital of Shandong University
🇨🇳Jinan, Shandong, China
Xiangya Hospital, Central South University
🇨🇳Changsha, China
Huashan Hospital Fudan University
🇨🇳Shanghai, Shanghai, China
Institute of Hematology and Blood Diseases Hospital
🇨🇳Heping, Tianjin, China
The 1st Affiliated Hosp of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
Peking University People's Hospital
🇨🇳Beijing, China
Peking University Third Hospital
🇨🇳Beijing, China
The First Hospital of Jilin University
🇨🇳Changchun, China
Chenzhou No.1 People's Hospital
🇨🇳Chenzhou, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, China
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, China
The First Affiliated Hospital of Sun Yat-sen University
🇨🇳Guangzhou, China
Nanfang Hospital of Southern Medical University
🇨🇳Guangzhou, China
The First Affiliated Hospital of Zhejiang University school of medicine
🇨🇳Hangzhou, China
Anhui Provincial Hospital
🇨🇳Hefei, China
The People's Hospital of Guangxi Zhuang Autonomous Region
🇨🇳Nanning, China
Shengjing Hospital of China Medical University
🇨🇳Shengyang, China
The Second Hospital of Hebei Medical University
🇨🇳Shijiazhuang, China
Xi'an International Medical Center
🇨🇳Xi'an, China
Henan Provincial People's Hospital
🇨🇳Zhengzhou, China
CHU de Besancon
🇫🇷Besançon, Doubs, France
Institut de Cancérologie de Strasbourg Europe - ICANS
🇫🇷Strasbourg, Bas Rhin, France
CHU Besançon - Hôpital Jean Minjoz
🇫🇷Besançon Cedex, Doubs, France
CHU Bordeaux Hopital Saint André
🇫🇷Bordeaux, Gironde, France
Universitatsklinikum Leipzig
🇩🇪Leipzig, Saxony, Germany
CHU de Rennes - Hôpital Pontchaillou
🇫🇷Rennes, Ille-et-Vilaine, France
CHU de Nantes CIC Hematologie
🇫🇷Nantes, Loire Atlantique, France
Hôpital Necker - Enfants Malades
🇫🇷Paris cedex 15, Paris, France
Charite Universitatsmedizin Berlin
🇩🇪Berlin, Germany
Universitaetsklinikum Koeln
🇩🇪Koeln, Germany
Soroka University Medical Center
🇮🇱Beer-Sheva, Israel
Hadassah University Hospital - Ein Kerem
🇮🇱Jerusalem, Israel
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Tel Aviv Sourasky Medical Center Pt
🇮🇱Tel Aviv, Israel
Azienda Ospedaliera Universitaria Luigi Vanvitelli
🇮🇹Napoli, Campania, Italy
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹Monza, Di Monza E Della Brianza, Italy
Azienda Ospedaliero Universitaria Pisana (Presidio di Cisanello)
🇮🇹Pisa, Italy
IRCCS Ospedale Policlinico San Martino
🇮🇹Genova, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
AOU Policlinico di Modena
🇮🇹Modena, Italy
Clinica Malattie Infettive Dipartimento di Medicina e Chirurgia dell'Università
🇮🇹Perugia, Italy
Inmi Lazzaro Spallanzani Irccs
🇮🇹Roma, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Italy
Chiba University Hospital
🇯🇵Chiba, Chiba Ken, Japan
Kyushu University Hospital
🇯🇵Fukuoka shi, Fukuoka Ken, Japan
Osaka Metropolitan University Hospital
🇯🇵Osaka, Osaka Fu, Japan
Tohoku University Hospital
🇯🇵Sendai-shi, Miyagi Ken, Japan
Osaka International Cancer Institute
🇯🇵Osaka shi, Osaka Fu, Japan
Kindai University Hospital
🇯🇵Ōsaka-sayama, Osaka Fu, Japan
The Jikei University Hospital
🇯🇵Minato-Ku, Tokyo, Japan
Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
🇯🇵Bunkyō-Ku, Japan
Toranomon Hospital
🇯🇵Minato-Ku, Tokyo To, Japan
Nagasaki University Hospital
🇯🇵Nagasaki, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
The Catholic University of Korea
🇰🇷Bucheon-si, Seoul, Korea, Republic of
Saitama Medical Center Jichi Medical University
🇯🇵Saitama, Japan
Jichi Medical University Hospital
🇯🇵Shimotsuke, Japan
Samsung Medical Center
🇰🇷Irwon-dong, Seoul, Korea, Republic of
Radboud Nijmegen
🇳🇱Nijmegen, Netherlands
UMC Utrecht
🇳🇱Utrecht, Netherlands
Auckland City Hospital
🇳🇿Auckland, New Zealand
National University Hospital
🇸🇬Singapore, Singapore
Wellington Regional Hospital
🇳🇿Newtown, Wellington, New Zealand
Singapore General Hospital- Parent
🇸🇬Singapore, Singapore
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Retiro, Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
China Medical University Hospital
🇨🇳Taichung, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Taipei Medical University - Shuang Ho Hospital, Ministry of Health and Welfare
🇨🇳New Taipei City, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Srinagarind Hospital
🇹🇭Khon Kaen, Thailand
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
Siriraj Hospital
🇹🇭Bangkok-noi, Bangkok, Thailand
Ankara City Hospital
🇹🇷Ankara, Turkey
Dicle University, Medical Faculty
🇹🇷Diyarbakir, Turkey
Ege University Medical Faculty
🇹🇷Izmir, Turkey
Acibadem Atakent Hospital
🇹🇷Istanbul, Turkey
Ondokuz Mayis Univ. Med. Fac.
🇹🇷Samsun, Turkey
Kings College Hospital
🇬🇧London, United Kingdom
Imperial College London
🇬🇧London, United Kingdom