Evaluate F901318 (Olorofim) Treatment of Invasive Fungal Infections in Participants Lacking Treatment Options (FORMULA-OLS)

Phase IIb Study of F901318 as Treatment of Invasive Fungal Infections Due to Lomentospora Prolificans, Scedosporium Spp., Aspergillus Spp., and Other Resistant Fungi in Patients Lacking Suitable Alternative Treatment Options

A study to evaluate olorofim (F901318) for the treatment of invasive fungal infections in participants lacking suitable alternative treatment options.

Study Overview

• Status: Completed
• Conditions: Invasive Fungal Infections
• Intervention / Treatment: Drug: Olorofim

Detailed Description

An open label, single arm Phase IIb study of olorofim (F901318) in participants with invasive fungal infections with limited treatment options. Participants received study treatment for up to 12 weeks in the main phase of the study. At the Investigator's request and after discussion with the medical monitor, open-label treatment with F901318 could be continued in patients judged by the Investigator to need therapy beyond 84 days and considered likely to continue to benefit from extended treatment.

• Study Type: Interventional
• Enrollment (Actual): 203
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Melbourne, Victoria, Australia, 3000
      • Royal Melbourne Hospital
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Centre-East Melbourne
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Belgium
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Bruxelles, Belgium, 1070
    • Hopital Erasme
  • Waals-Brabant
    • Leuven, Waals-Brabant, Belgium, 3000
      • UZ Leuven
• Brazil
  • Curitiba, Brazil, 81520-060
    • Hospital Erasto Gaertner - Liga Paranaense de Combate Ao Cancer
  • Passos, Brazil, 37904-020
    • Santa Casa de Misericordia de Passos
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-221
      • Santa Casa de Misericordia de Belo Horizonte
    • Belo Horizonte, Minas Gerais, Brazil, 30110-934
      • Hospital Felício Rocho
  • Paraná
    • Curitiba, Paraná, Brazil, 80060-900
      • HC - UFPR - Hospital de Clínicas da Universidade Federal do Paraná
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital De Clinicas De Porto Alegre
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Hospital São Lucas da PUCRS
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90020-090
      • 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
• Egypt
  • Alexandria, Egypt, 21131
    • Alexandria University Hospital
  • Cairo, Egypt, 11566
    • Ain Shams University Hospital
  • Cairo, Egypt, 11796
    • National Cancer Institute
  • Cairo, Egypt, 12655
    • Nasser Institute
  • Cairo, Egypt, 11559
    • Cairo University Hospitals
  • Cairo, Egypt, 11566
    • Air Force Specialized Hospital
  • Mansoura, Egypt, 35516
    • Oncology Center, Mansoura University
• France
  • Paris cedex 10, France, 75475
    • Hôpital Saint-Louis
  • Bas Rhin
    • Strasbourg cedex, Bas Rhin, France, 67091
      • CHU Strasbourg - Hopital Hautepierre
  • Isere
    • Grenoble, Isere, France, 38043
      • CHU de Grenoble - Hopital Albert Michallon
  • Paris
    • Paris cedex 15, Paris, France, 75015
      • Hôpital Necker - Enfants Malades
• Germany
  • Berlin, Germany, 12200
    • Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
  • Berlin, Germany, 12200
    • Charite-Campus Benjamin Franklin (CBF)
  • Bayern
    • Muenchen, Bayern, Germany, 81377
      • Klinikum der Universitaet Muenchen Campus Grosshadern
  • Nordrhein Westfalen
    • Koeln, Nordrhein Westfalen, Germany, 50937
      • Universitaetsklinikum Koeln
• Israel
  • Beer-Sheva, Israel, 84001
    • Soroka University Medical Center
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital - Ein Kerem
  • Ramat Gan, Israel, 52363
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Radboudumc
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus Medisch Centrum
  • Utrecht, Netherlands, 3584 CX
    • UMC Utrecht
• Poland
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Krakow, Poland, 31-501
    • SPZOZ Szpital Uniwersytecki w Krakowie
  • Slupsk, Poland, 76-200
    • Wojewodzki Szpital Specjalistyczny im. J. Korczaka
  • Warszawa, Poland, 02-776
    • Instytut Hematologii i Transfuzjologii
• Russian Federation
  • Saint Petersburg, Russian Federation
    • FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
  • Saint Petersburg, Russian Federation, 194291
    • Leningrad Regional Clinical Hospital
  • Saint Petersburg, Russian Federation
    • Pavlov First Saint Petersburg State Medical University
  • Saint Petersburg, Russian Federation
    • SBEIHPE "NWSMU n. a. I.I Mechnikov" of MoH and SD of RH
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Valencia, Spain, 46021
    • Hospital Universitari i Politecnic La Fe
• Thailand
  • Bangkok
    • Bangkoknoi, Bangkok, Thailand, 10700
      • Siriraj Hospital
    • Pathum Wan, Bangkok, Thailand, 10330
      • King Chulalongkorn Memorial Hospital
• Turkey
  • Diyarbakır, Turkey, 21280
    • Dicle University, Medical Faculty
  • Istanbul, Turkey, 34899
    • Marmara University Pendik Research and Training Hospital
  • Istanbul, Turkey, 34303
    • Acibadem Atakent Hospital
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, SE5 9NU
      • King's College Hospital
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M13 9WL
      • Manchester Royal Infirmary
  • Wythenshawe
    • Manchester, Wythenshawe, United Kingdom, M23 9LT
      • Wythenshawe Hospital
• United States
  • California
    • Bakersfield, California, United States, 93306
      • Valley Fever Institute at Kern Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • San Diego, California, United States, 92103
      • University of California San Diego Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • Stony Brook, New York, United States, 11794-0001
      • Stony Brook University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Health System
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • The University of Texas Health Science Center at San Antonio
• Vietnam
  • Hanoi, Vietnam, 100000
    • Bach Mai Hospital
  • Hanoi, Vietnam, 10000
    • National Lung Hospital
  • Ho Chi Minh, Vietnam, 00000
    • HCMC Hospital for Tropical Diseases
  • Ho Chi Minh, Vietnam, 0000
    • Blood Transfusion Hematology Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female aged at least 18 years, or male and female aged 16 years or 17 years and who weigh at least 40 kg whom have given informed consent
• Ability and willingness to comply with the protocol.
• Able to take oral medication
• Females must be non-lactating and at no risk of pregnancy
• Male with female partners of childbearing potential must either abstain from sexual intercourse or use a highly effective means of contraception
• Participants with invasive fungal disease
• Participants who have limited alternative treatment options

Exclusion Criteria:

• Women who are pregnant or breastfeeding.
• Known history of allergy, hypersensitivity, or any serious reaction to any component of the study drug.
• Participants with chronic aspergillosis, aspergilloma or allergic bronchopulmonary aspergillosis.
• Human Immunodeficiency Virus (HIV) infection but not currently receiving antiretroviral therapy.
• Participants with a medical condition that may jeopardize adherence to the protocol or may cause unacceptable additional risk to the participant
• Previously enrolled participants or participants enrolled in any clinical trial within the last 30 days
• Participants receiving treatment limited to supportive care due to predicted short survival time.
• Prohibited concomitant medications.
• Any exclusion criteria required by local regulatory authorities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Olorofim (F901318); Olorofim (F901318) was given orally for up to 90 days in the Main Study Phase and could be continued for those participants entering the Extended Treatment Phase. Patients received fixed doses comprising of a 1-day loading dose of 150 mg of olorofim twice a day followed by a maintenance dose of 90 mg of olorofim twice a day. Up until Protocol Amendment 06, 58 patients received a weight-based olorofim dosing consisting of a 1-day loading dose of 4 mg/kg/day on Day 1, then a maintenance dose of 2.5 mg/kg/day (divided into 2 or 3 doses). The dose was then adjusted based on plasma levels of olorofim with the maximum total daily dose of 300 mg.

Drug: Olorofim; 30mg oral tablets; Other Names: F901318

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Data Review Committee (DRC) Adjudicated Overall Response at Day 42	The primary efficacy variable was the DRC-adjudicated overall response at the Day 42 Study Visit, as determined by an independent DRC using a combination of clinical, mycological, and radiological results based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. For the primary statistical analysis of overall response rate, values were assigned to the DRC adjudicated overall response as follows: Success (Success-Complete, Success-Partial); Failure (Failure-Stable, Failure-Progression, Death, and participants for whom data at the Day 42 Study Visit could not be collected or participants who were considered not evaluable at the Day 42 Study Visit).	Day 42 in the Main Phase of study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DRC Adjudicated Overall Response at Day 42 for All Aspergillus	The primary efficacy variable was the DRC-adjudicated overall response at the Day 42 Study Visit, as determined by an independent DRC using a combination of clinical, mycological, and radiological results based on EORTC/MSG criteria. This was also presented by each of the 5 major infections as adjudicated by the DRC at baseline. The Aspergillus- All category is a combination of participants with Aspergillus proven and Aspergillus probable (invasive aspergillosis lower respiratory tract disease) baseline disease category. Overall success is defined as a Complete or Partial Response.	Day 42 in the Main Phase of study treatment
DRC Adjudicated Overall Response at Day 42 for Lomentospora Prolificans	The primary efficacy variable was the DRC-adjudicated overall response at the Day 42 Study Visit, as determined by an independent Data Review Committee using a combination of clinical, mycological, and radiological results based on EORTC/MSG criteria. This was also presented by each of the 5 major infections as adjudicated by the DRC at baseline, this one is for participants with a proven infection due to Lomentospora prolificans. Success is defined as a Complete or Partial Response.	Day 42 in the Main Phase of study treatment Day 42 in the Main Phase of study treatment Day 42 in the Main Phase of study treatment Day 42 in the Main Phase of study treatment Day 42 in the Main Phase of study treatment
DRC Adjudicated Overall Response at Day 42 for for Scedosporium Species	The primary efficacy variable was the DRC-adjudicated overall response at the Day 42 Study Visit, as determined by an independent DRC using a combination of clinical, mycological, and radiological results based on EORTC/MSG criteria. This was also presented by each of the 5 major infections as adjudicated by the DRC at baseline, this one is for participants with a proven infection due to Scedosporium species. Success is defined as a Complete or Partial Response.	Day 42 in the Main Phase of study treatment
DRC Adjudicated Overall Response at Day 42 for Coccidioides Species	The primary efficacy variable was the DRC-adjudicated overall response at the Day 42 Study Visit, as determined by an independent DRC using a combination of clinical, mycological, and radiological results based on EORTC/MSG criteria. This was also presented by each of the 5 major infections as adjudicated by the DRC at baseline, this one is for participants with proven infection due to Coccidioides species. Success is defined as a Complete or Partial Response.	Day 42 in the Main Phase of study treatment
DRC Adjudicated Overall Response at Day 42 for Other Olorofim Susceptible Fungi	The primary efficacy variable was the DRC-adjudicated overall response at the Day 42 Study Visit, as determined by an independent DRC using a combination of clinical, mycological, and radiological results based on EORTC/MSG criteria. This was also presented by each of the 5 major infections as adjudicated by the DRC at baseline, this one is for participants with proven infection due to other olorofim susceptible fungi. Success is defined as a Complete or Partial Response.	Day 42 in the Main Phase of study treatment
DRC Adjudicated Overall Response at Day 84	DRC-adjudicated overall response at Day 84, as determined by an independent DRC using a combination of clinical, mycological, and radiological results based on the EORTC/MSG criteria. For the analysis of overall response rate, values were assigned to the DRC-adjudicated overall response as follows: Success (Success-Complete, Success-Partial); Failure (Failure-Stable, Failure-Progression, Death, and participants for whom data at the Study Visit could not be collected or participants who were considered not evaluable at the Study Visit).	Day 84 in the Main Phase of study treatment
Investigator Assessed Overall Response at Day 42	Investigator-assessed overall response (as determined by the Investigator using all available assessment results including clinical, mycological and radiologic results based on the EORTC/MSG criteria) at Day 42, categorised by the same response criteria as in the primary endpoint: Success (Success-Complete, Success-Partial), Failure (Failure-Stable, Failure-Progression, Death, participants for whom data at Day 42 could not be collected or who were considered not evaluable at the specific visit).	Day 42 in the Main Phase of study treatment
Investigator Assessed Overall Response at Day 84	Investigator-assessed overall response (as determined by the Investigator using all available assessment results including clinical, mycological and radiologic results based on the EORTC/MSG criteria) at Day 84, categorised by the same response criteria as in the primary endpoint: Success (Success-Complete, Success-Partial), Failure (Failure-Stable, Failure-Progression, Death, participants for whom data at Day 84 could not be collected or who were considered not evaluable at the specific visit).	Day 84 in the Main Phase of study treatment
DRC Adjudicated Clinical Response at Day 42	DRC adjudicated clinical response at the Day 42 Study Visit, as determined by an independent Data Review Committee using clinical response results based on EORTC/MSG criteria. Resolution is defined as a Complete or Partial Response.	Day 42 in the Main phase of study treatment
DRC Adjudicated Clinical Response at Day 84	DRC adjudicated clinical response at the Day 84 Study Visit, as determined by an independent DRC using clinical response results based on EORTC/MSG criteria. Resolution is defined as a Complete or Partial Response.	Day 84 in the Main phase of study treatment
Investigator Assessed Clinical Response at Day 42	Investigator assessed clinical response at the Day 42 Study Visit using clinical response results based on the EORTC/MSG criteria. Resolution is defined as a Complete or Partial Response.	Day 42 in the Main phase of study treatment
Investigator Assessed Clinical Response at Day 84	Investigator assessed clinical response at the Day 84 Study Visit using clinical response results based on the EORTC/MSG criteria. Resolution is defined as a Complete or Partial Response.	Day 84 in the Main Phase of study treatment
DRC Adjudicated Mycological Response at Day 42	DRC adjudicated mycological response was assessed at the Day 42 Study Visit, as determined by an independent Data Review Committee using mycological response results based on EORTC/MSG criteria. Success is defined as eradication or presumed eradication.	Day 42 in the Main Phase of study treatment
DRC Adjudicated Mycological Response at Day 84	DRC adjudicated mycological response was assessed at the Day 84 Study Visit, as determined by an independent DRC using mycological response results based on EORTC/MSG criteria. Success is defined as eradication or presumed eradication.	Day 84 in the Main phase of study treatment
Investigator Assessed Mycological Response at Day 42	Mycological response was assessed by the Investigator at the Day 42 Study Visit using mycological response results based on EORTC/MSG criteria. Success is defined as eradication or presumed eradication.	Day 42 in the Main Phase of study treatment
Investigator Assessed Mycological Response at Day 84	Mycological response was assessed by the Investigator at the Day 84 Study Visit using mycological response results based on EORTC/MSG criteria. Success is defined as eradication or presumed eradication.	Day 84 in the Main Phase of study treatment
DRC Adjudicated Radiological Response at Day 42	In participants for whom radiology formed a part of their diagnosis, radiology evaluations were required on Day 42 and were adjudicated by an independent DRC. Radiological responses were assigned as per EORTC/MSG criteria.	Day 42 in the Main phase of study treatment
DRC Adjudicated Radiological Response at Day 84	In participants for whom radiology formed a part of their diagnosis, radiology evaluations were required on Day 84 and were adjudicated by an independent DRC. Radiological responses were assigned as per EORTC/MSG criteria.	Day 84 in the Main Phase of study treatment
Investigator Assessed Radiological Response at Day 42	In participants for whom radiology formed a part of their diagnosis, radiology evaluations were required on Day 42. Radiological responses were assessed by the Investigator using EORTC/MSG criteria.	Day 42 in the Main Phase of study treatment
Investigator Assessed Radiological Response at Day 84	In participants for whom radiology formed a part of their diagnosis, radiology evaluations were required on Day 84. Radiological responses were assessed by the Investigator using EORTC/MSG criteria.	Day 84 in the Main Phase of study treatment
All Cause Mortality Rate at Day 42	The all cause mortality rate at Day 42 uses the survival status that was entered at the study visit (which employs a window around each nominal study day).	Day 42 in the Main Phase of study treatment
All Cause Mortality Rate at Day 84	The all cause mortality rate at Day 84 uses the survival status that was entered at the study visit (which employs a window around each nominal study day).	Day 84 in the Main Phase of study treatment

Collaborators and Investigators

• Sponsor: F2G Biotech GmbH
• Collaborators: IQVIA Pty Ltd
• Investigators: Principal Investigator: Sharon Chen, Westmead Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2018
• Primary Completion (Actual): February 10, 2023
• Study Completion (Actual): February 10, 2023

Study Registration Dates

• First Submitted: May 17, 2018
• First Submitted That Met QC Criteria: July 10, 2018
• First Posted (Actual): July 11, 2018

Study Record Updates

• Last Update Posted (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Coccidioidomycosis; Anti fungal; Invasive aspergillosis; Rare moulds
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Mycoses; Invasive Fungal Infections; Anti-Infective Agents; Antifungal Agents; Olorofim
• Other Study ID Numbers: F901318/0032

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results can be available to researchers after the primary publication of results for this study, after deidentification (text, tables, figures, appendices)
• IPD Sharing Time Frame: From 3 months after publication of the primary manuscript (no end date)
• IPD Sharing Access Criteria: Requests should be directed to F2G for review.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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