Treatment of invasive fungal infections (IFI) in adults with limited or no treatment options or intolerant to available therapy, including: refractory or resistant aspergillosis, and lomentosporiosis, scedosporiosis, Scopulariopsis infections.
Conditions
Interventions
Olorofim Group:Olorofim Tablet
Sponsors
Nanfang Hospital of Southern Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Participants between ages of 18 and 55 years (inclusive) at the time of signing informed consent. 2. Participants with body weight of 45 to 100 kg and body mass index of 18 to 30 kg/m² (inclusive). 3. Participants must be in good health, as determined by a medical history, physical examination, 12-lead electrocardiogram (ECG), and clinical laboratory evaluations. 4. Participants born in China who have/had 4 ethnic Chinese grandparents, hold a Chinese passport or identity papers, and are able to speak Chinese. Participants should have lived outside China for less than 5 years at the time of screening. 5. Participants capable of giving signed informed consent as described in Informed Consent Process, that includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 6. Male and female participants a. Male participants: Male participants are eligible to participate if they agree to the following from Day-1 until at least 30 days after the dose of olorofim: # Refrain from donating fresh unwashed semen. PLUS either: # Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR # Must agree to use contraception as detailed below. - Agree to use a male condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak) when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. b. Female participants: # A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: - Is a woman of non-childbearing potential (WONCBP) as defined in in Section 10.4 Contraception and Barrier Guidance. OR - Is a WOCBP and using a contraceptive method from screening until at least 30 days after the dose of olorofim that is highly effective, with low user dependency, as described in Section 10.4 Contraception and Barrier Guidance. The investigator should evaluate the potential for contraceptive method failure (eg, non-compliance, recently initiated) relative to olorofim dosing. # A WOCBP must have a negative highly sensitive pregnancy test at screening and within 24 hours before receiving the dose of olorofim (see Section 8.2.5 Pregnancy Testing). - If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. # Additional requirements for pregnancy testing during and after olorofim administration are located in Section 8.2.5 Pregnancy Testing. # The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Exclusion criteria
Exclusion criteria: 1. Participants have had surgery that may affect drug absorption, distribution, metabolism, or excretion. 2. Participants with, or with a history of, any clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking olorofim; or interfering with the interpretation of data. 3. Participants with resting systolic BP outside the range of 90 to 140 mmHg, resting diastolic BP outside the range of 60 to 90 mmHg, or pulse rate outside the range of 50 to 100 bpm at screening or Day 1 predose, and considered ineligible by the investigator. 4. Participants who have hypersensitivity to any of the study interventions or components thereof, or drug or any other clinically significant allergy as considered ineligible by the investigator (excluding mild or seasonal allergies such as contact dermatitis or hay fever). 5. Participants who had lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. 6. Participants with any clinically relevant history of convulsion (other than childhood febrile convulsion before the age of 6 years), syncope, hypotension, dizziness, and fainting. 7. Participants taking concomitant medications known to inhibit or induce CYP2C9 or CYP3A4 within 30 days or 5 half-lives, whichever is longer, prior to screening. 8. Participants who are scheduled to use or have used over-the-counter drugs or prescription drugs (including vitamins, minerals, Chinese herbal medicines, and supplements [St. John’s wort, etc.]) within 14 days prior to Day-1. 9. Participants in need of drug therapy or other treatment (eg, physical therapy, etc.) or have a dietary restriction. 10. Participants who are still participating in a clinical study (eg, attending follow-up visits) or who have participated in an interventional clinical study involving administration of an investigational drug (new chemical or biological entity) within 30 days or 5 half-lives, whichever is longer, prior to screening. 11. Previous exposure to olorofim. 12. Participants with hepatic transaminases or total bilirubin above the upper limit of normal (ULN) at screening or Day-1 (repeat analysis is not permitted). 13. Participants who have an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risk of participating in the study, such as QTcF interval >450 msec, 2nd or 3rd degree atrioventricular block, complete left bundle branch block, complete right bundle branch block or Wolff-Parkinson-White Syndrome, as confirmed by repeat ECG. 14. Participants with a history of alcohol abuse within 6 months prior to screening or with a positive alcohol breath test at screening or Day -1. 15. Participants with a history of drug abuse within 6 months prior to screening or with a positive drugs of abuse test at screening or Day -1. 16. Participants with presence of hepatitis B surface antigen (HBsAg) (or hepatitis B virus core antibody [HBcAb]) at screening or within 3 months prior to screening. 17. Participants with positive hepatitis C virus antibody test result at screening or within 3 months prior to screening. NOTE: Participants with positive hepatitis C virus antibody due to prior resolved disease can be enrolled if
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax and AUC0-last of Olorofim;Tmax, AUC0-inf, MRT, Vz/F, CL/F, t1/2, z, ?z of Olorofim;F902412 and H26C (R- and S-enantiomers): Tmax, Cmax, AUC0-last, AUC0-inf, t1/2,z, ?z, MRCmax, and MRAUC.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Adverse events, vital signs measurements, safety laboratory tests (hematology, blood chemistry, coagulation, and urinalysis), and ECG findings.; | — |
Countries
China
Contacts
Public ContactZhongyuan Xu
Nanfang Hospital of Southern Medical University
Outcome results
None listed