Rezafungin for Treatment of Pneumocystis Pneumonia in HIV Adults

Inclusion Criteria:

1. Males or females at least 18 years of age.

2. Tested positive for HIV by either blood antigen/antibody combination HIV-1/2immunoassay, HIV-1/HIV-2 antibody differentiation immunoassay, or nucleic acid tests (e.g., HIV ribonucleic acid [RNA] polymerase chain reaction [PCR]). Participants whoare newly diagnosed with HIV infection by an antigen/antibody combination HIV-1/2immunoassay are allowed to be included in the study, but the infection should besubsequently confirmed by an HIV-1/HIV-2 antibody differentiation immunoassay ornucleic acid tests.

3. Diagnosed with definitive, presumptive, or clinically suspected PCP prior torandomisation.

4. Willing and able to provide written informed consent. If the participant is unableto provide consent, a legally acceptable representative (i.e., acceptable to ICH andlocal law, as applicable) must provide informed consent on the participant's behalf.

5. Participants of childbearing potential (all biologically female participants between 18 years and <2 years post-menopausal unless surgically sterile) must agree to use ahighly effective contraceptive measure during the study period (from enrolment) andfor at least 30 days after the last dose of rezafungin.

6. Biologically male participants who are not vasectomised must agree to the followingrequirements during the study period (from enrolment) and for at least 120 daysafter the last dose of rezafungin:

• Refrain from donating sperm PLUS, either

• Abstain from sexual intercourse with a female of childbearing potential astheir preferred and usual lifestyle OR

• Use barrier contraception (i.e., male condom with or without spermicide) whenhaving sexual intercourse with a female of childbearing potential who is notcurrently pregnant.

Exclusion Criteria:

1. Under 18 years of age.

2. Known or suspected hypersensitivity or allergic reaction to co-trimoxazole,rezafungin, any echinocandin, or any component of these formulations, including, butnot limited to, anaphylaxis or exfoliative skin disorders (e.g., Stevens-Johnsonsyndrome or toxic epidermal necrolysis).

3. Any contraindication to co-trimoxazole or intake of a medication or supplement knownto severely interact with co-trimoxazole as detailed in the Summary of ProductCharacteristics (SmPC) of co-trimoxazole, including, but not limited to, acuteporphyria or a history of drug-induced immune thrombocytopaenia with use oftrimethoprim and/or sulphonamides.

4. Creatinine clearance <15 mL/min or receiving renal replacement therapy.

5. Severe hepatic impairment, defined as aspartate aminotransferase (AST) or alanineaminotransferase (ALT) >5 × upper limits of normal (ULN), or total bilirubin >3 ×ULN, or a history of chronic cirrhosis (Child-Pugh score >9).

6. A neutrophil count <1,000 cells/µL or a platelet count <50,000 cells/µL.

7. Immunosuppressive disease other than HIV / acquired immunodeficiency syndrome (AIDS) (e.g., haematopoietic stem cell transplant, solid organ transplant, or primaryimmune deficiencies) OR prolonged use of immune-weakening medications:

• Having received corticosteroids equivalent to prednisone ≥20 mg daily for atleast 14 consecutive days within 30 days prior to study entry, or

• Having received biologics (e.g., infliximab, ustekinumab), immunomodulators (e.g., methotrexate, mercaptopurine, azathioprine), or cancer chemotherapywithin 90 days prior to study entry.

8. Previously diagnosed with PCP and having received treatment in the past 6 weeks.

9. Receiving therapy for PCP at approved therapeutic doses for >48 hours beforerandomisation. Exception: receipt of an anti-PCP drug at prophylactic doses (i.e.,lower than approved therapeutic doses).

10. Meeting National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 criteria for ataxia, tremors, motor neuropathy, or sensoryneuropathy of Grade 2 or higher.

11. History of severe ataxia, tremors, or neuropathy or a diagnosis of multiplesclerosis or a movement disorder (including Parkinson's disease and Huntington'sdisease).

12. Planned or ongoing therapy at Screening with a known severe neurotoxic medication orwith a known moderate neurotoxic medication in a participant with ataxia, tremors,motor neuropathy, or sensory neuropathy of NCI-CTCAE version 5.0 Grade 1 or higher.

13. Previous participation in this or any other rezafungin study.

14. Female participants who are pregnant or lactating.

15. Having a concomitant disease or any medical condition (including otherHIV-associated infection or complication) that, in the opinion of the Investigator,could pose undue risk to the participant, impede completion of the study procedures (e.g., patients who are not expected to survive even with treatment), or wouldcompromise the validity of the study measurements.

16. Receipt of an investigational drug within 30 days prior to dosing of the studydrug(s), presence of an investigational device at the time of Screening, or isplanning to participate in another interventional clinical study while enrolled inthis study.

17. The Investigator is of the opinion the participant should not participate in thestudy.

Late Exclusion Criteria:

The diagnosis of PCP will be reviewed by the Investigator on Day 8 (before dosing the study drug). Participants will be withdrawn from the study if any of the following criteria apply (i.e., participants without a diagnosis of definitive or presumptive PCP on Day 8):

1. Lack of positive P. jirovecii immunofluorescence or PCR of bronchoalveolar lavage,endotracheal aspirates, bronchoscopic tissue biopsy, or induced sputum AND serum β-D-glucan below the positive cut-off value.

2. Serum β-D-glucan below the positive cut-off value in participants in whom collectionof a suitable respiratory sample is not possible.

3. Radiographic features on chest CT performed after randomisation not consistent withPCP after taking into account the clinical and microbiological findings.