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NCT03583164: FORMULA-OLS

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

Completed Phase 2 Results posted Last updated 10 July 2024
What this trial tests

Phase 2 trial testing Olorofim in Invasive Fungal Infections in 203 participants. Completed in 10 February 2023.

Timeline
6 June 2018
Primary endpoint
10 February 2023
10 February 2023

Quick facts

Lead sponsorF2G Biotech GmbH
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment203
Start date6 June 2018
Primary completion10 February 2023
Estimated completion10 February 2023
Sites82 locations across France, Netherlands, Russia, Turkey (Türkiye), Belgium, United Kingdom, Germany, Israel

Drugs / interventions tested

Conditions studied

Sponsor

F2G Biotech GmbH — full company profile →

Who can join

16 and older, any sex, with Invasive Fungal Infections. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Data Review Committee (DRC) Adjudicated Overall Response at Day 42 Primary · Day 42 in the Main Phase of study treatment

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

GroupValue95% CI
Olorofim (F901318)28.722.6 – 35.5
DRC Adjudicated Overall Response at Day 42 for All Aspergillus Secondary · Day 42 in the Main Phase of study treatment

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.

GroupValue95% CI
Olorofim (F901318)34.725.5 – 44.8
DRC Adjudicated Overall Response at Day 42 for Lomentospora Prolificans Secondary · 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

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.

GroupValue95% CI
Olorofim (F901318)42.323.4 – 63.1
DRC Adjudicated Overall Response at Day 42 for for Scedosporium Species Secondary · Day 42 in the Main Phase of study treatment

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.

GroupValue95% CI
Olorofim (F901318)36.417.2 – 59.3
DRC Adjudicated Overall Response at Day 42 for Coccidioides Species Secondary · Day 42 in the Main Phase of study treatment

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.

GroupValue95% CI
Olorofim (F901318)0.00.0 – 8.6
DRC Adjudicated Overall Response at Day 42 for Other Olorofim Susceptible Fungi Secondary · Day 42 in the Main Phase of study treatment

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.

GroupValue95% CI
Olorofim (F901318)33.39.9 – 65.1
DRC Adjudicated Overall Response at Day 84 Secondary · Day 84 in the Main Phase of study treatment

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).

GroupValue95% CI
Olorofim (F901318)27.221.2 – 33.9
Investigator Assessed Overall Response at Day 42 Secondary · Day 42 in the Main Phase of study treatment

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).

GroupValue95% CI
Olorofim (F901318)24.819.0 – 31.3
Investigator Assessed Overall Response at Day 84 Secondary · Day 84 in the Main Phase of study treatment

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).

GroupValue95% CI
Olorofim (F901318)29.723.5 – 36.5
DRC Adjudicated Clinical Response at Day 42 Secondary · Day 42 in the Main phase of study treatment

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.

GroupValue95% CI
Olorofim (F901318)59.952.8 – 66.7
DRC Adjudicated Clinical Response at Day 84 Secondary · Day 84 in the Main phase of study treatment

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.

GroupValue95% CI
Olorofim (F901318)54.046.8 – 61.0
Investigator Assessed Clinical Response at Day 42 Secondary · Day 42 in the Main phase of study treatment

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.

GroupValue95% CI
Olorofim (F901318)53.546.3 – 60.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs) were reported from the time of Informed consent through study completion, up to and including 4-week post-treatment follow-up. For patients in the main treatment phase of the study only, the median duration of study treatment was 84 days. For those entering the extended treatment phase, the median duration of study treatment was 308 days (approximately 10 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Olorofim (F901318)
Serious: 132/203 (65%)
Deaths: 50/203

Serious adverse events (194 terms)

ReactionSystemOlorofim (F901318)
PneumoniaInfections and infestations
PyrexiaGeneral disorders
COVID-19Infections and infestations
Respiratory failureRespiratory, thoracic and mediastinal disorders
Hepatic enzyme increasedInvestigations
Liver function test increasedInvestigations
DyspnoeaRespiratory, thoracic and mediastinal disorders
Meningitis coccidioidesInfections and infestations
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Aspergillus infectionInfections and infestations
SeizureNervous system disorders
Septic shockInfections and infestations
Acute kidney injuryRenal and urinary disorders
Acute myeloid leukaemia refractoryNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Atrial fibrillationCardiac disorders
HeadacheNervous system disorders
HydrocephalusNervous system disorders
Pneumonia viralInfections and infestations
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
Acute myeloid leukaemiaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Back painMusculoskeletal and connective tissue disorders
Bacterial infectionInfections and infestations
Cerebral haemorrhageNervous system disorders
Other adverse events (28 terms — click to expand)

ReactionSystemOlorofim (F901318)
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
HeadacheNervous system disorders
PyrexiaGeneral disorders
Liver function test increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
Oedema peripheralGeneral disorders
COVID-19Infections and infestations
FatigueGeneral disorders
Hepatic enzyme increasedInvestigations
Urinary tract infectionInfections and infestations
HypokalaemiaMetabolism and nutrition disorders
HypotensionVascular disorders
Acute kidney injuryRenal and urinary disorders
ArthralgiaMusculoskeletal and connective tissue disorders
ConstipationGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Back painMusculoskeletal and connective tissue disorders
Decreased appetiteMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
DepressionPsychiatric disorders
Pain in extremityMusculoskeletal and connective tissue disorders
AnaemiaBlood and lymphatic system disorders
HyponatraemiaMetabolism and nutrition disorders
HyperkalaemiaMetabolism and nutrition disorders
HypertensionVascular disorders
RashSkin and subcutaneous tissue disorders

Most-reported serious reactions: Pneumonia, Pyrexia, COVID-19, Respiratory failure, Hepatic enzyme increased, Liver function test increased, Dyspnoea, Meningitis coccidioides.

Data from ClinicalTrials.gov NCT03583164 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin.
    Hoenigl M, Sprute R, Egger M, Arastehfar A, et al · · 2021 · cited 303× · PMID 34626339 · DOI 10.1007/s40265-021-01611-0
  2. Antifungal Drugs.
    Houšť J, Spížek J, Havlíček V. · · 2020 · cited 157× · PMID 32178468 · DOI 10.3390/metabo10030106
  3. Aspiring Antifungals: Review of Current Antifungal Pipeline Developments.
    Gintjee TJ, Donnelley MA, Thompson GR. · · 2020 · cited 152× · PMID 32106450 · DOI 10.3390/jof6010028
  4. Hope on the Horizon: Novel Fungal Treatments in Development.
    Rauseo AM, Coler-Reilly A, Larson L, Spec A. · · 2020 · cited 142× · PMID 32099843 · DOI 10.1093/ofid/ofaa016
  5. Review of the Novel Investigational Antifungal Olorofim.
    Wiederhold NP. · · 2020 · cited 102× · PMID 32751765 · DOI 10.3390/jof6030122
  6. Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease.
    Hoenigl M, Arastehfar A, Arendrup MC, Brüggemann R, et al · · 2024 · cited 86× · PMID 38602408 · DOI 10.1128/cmr.00074-23
  7. Advancements and challenges in antifungal therapeutic development.
    Puumala E, Fallah S, Robbins N, Cowen LE. · · 2024 · cited 62× · PMID 38294218 · DOI 10.1128/cmr.00142-23
  8. COVID-19 Associated Invasive Pulmonary Aspergillosis: Diagnostic and Therapeutic Challenges.
    Mohamed A, Rogers TR, Talento AF. · · 2020 · cited 55× · PMID 32707965 · DOI 10.3390/jof6030115

Verify or expand the search:

Other trials of Olorofim

Trials testing the same drug.

Other recruiting trials for Invasive Fungal Infections

Currently open trials in the same condition.

Other F2G Biotech GmbH trials

Trials by the same sponsor.

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