Rezafungin for Treatment of Pneumocystis Pneumonia in HIV Adults

NCT05835479 | Recruiting Phase 2 DMC

• 1 other identifier: MR907-2501
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 6

Brief Summary

This study aims to generate clinical data on the efficacy, safety, and tolerability of rezafungin combined with 7 days of co-trimoxazole for treatment of Pneumocystis pneumonia (PCP) in adults living with human immunodeficiency virus (HIV), which would expand the knowledge of clinical use of rezafungin.

Conditions

Pneumocystis Pneumonia

Outcome Measures

Primary Outcomes (1)

• Therapeutic failure on Day 8

  Therapeutic failure on Day 8, defined by one of the following and confirmed by an independent, blinded Data Review Committee (DRC): * Clinical deterioration. The deterioration cannot be solely explained by other infections or causes and is defined as an increase in score of 2 points or more from the score prior to randomisation on Day 1 on the Ordinal Scale for Clinical Improvement (OSCI), as assessed by the Investigator. * Requirement for alternative primary therapy for PCP, or intensification of corticosteroid therapy, due to lack of efficacy (as assessed by the Investigator). * Death from any cause.

  8 days

Secondary Outcomes (1)

• Therapeutic failure at any time during the treatment period (from Day 1 to Day 21)

  21 days

Study Arms (2)

Rezafungin Acetate /Co-trimoxazole

EXPERIMENTAL

Rezafungin: Weekly intravenous infusion with a loading dose of 400 mg over 1 hour (±10 minutes) on Day 1 followed by maintenance doses of 200 mg over 1 hour (±10 minutes) on Day 8 and Day 15. From Day 1 to Day 7, co-trimoxazole will also be given with trimethoprim 15-20 mg/kg/day and sulfamethoxazole 75-100 mg/kg/day. For participants with a creatinine clearance between 15 mL/min and 30 mL/min, the dose of co-trimoxazole should be reduced to trimethoprim 7.5-10 mg/kg/day and sulfamethoxazole 37.5-50 mg/kg/day

Drug: Rezafungin Acetate / Co Trimoxazole

Co-trimoxazole

ACTIVE COMPARATOR

From Day 1 to Day 21, co-trimoxazole will be given with trimethoprim 15-20 mg/kg/day and sulfamethoxazole 75-100 mg/kg/day. For participants with a creatinine clearance between 15 mL/min and 30 mL/min, the dose of co-trimoxazole should be reduced to trimethoprim 7.5-10 mg/kg/day and sulfamethoxazole 37.5-50 mg/kg/day

Drug: Co-Trimoxazole

Interventions

Co-Trimoxazole DRUG

Oral co-trimoxazole or Intravenous (IV) co-trimoxazole for infusion. Anti fungal medication

Co-trimoxazole

Rezafungin Acetate / Co Trimoxazole DRUG

Rezafungin for infusion. Intravenous anti fungal therapy Oral co-trimoxazole or Intravenous (IV) co-trimoxazole for infusion. Anti fungal medication

Rezafungin Acetate /Co-trimoxazole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females at least 18 years of age.
• Tested positive for HIV by either blood antigen/antibody combination HIV-1/2 immunoassay, HIV-1/HIV-2 antibody differentiation immunoassay, or nucleic acid tests (e.g., HIV ribonucleic acid \[RNA\] polymerase chain reaction \[PCR\]). Participants who are newly diagnosed with HIV infection by an antigen/antibody combination HIV-1/2 immunoassay are allowed to be included in the study, but the infection should be subsequently confirmed by an HIV-1/HIV-2 antibody differentiation immunoassay or nucleic acid tests.
• Diagnosed with definitive, presumptive, or clinically suspected PCP prior to randomisation.
• Willing and able to provide written informed consent. If the participant is unable to provide consent, a legally acceptable representative (i.e., acceptable to ICH and local law, as applicable) must provide informed consent on the participant's behalf.
• Participants of childbearing potential (all biologically female participants between 18 years and \<2 years post-menopausal unless surgically sterile) must agree to use a highly effective contraceptive measure during the study period (from enrolment) and for at least 30 days after the last dose of rezafungin.
• Biologically male participants who are not vasectomised must agree to the following requirements during the study period (from enrolment) and for at least 120 days after the last dose of rezafungin:
• Refrain from donating sperm PLUS, either
• Abstain from sexual intercourse with a female of childbearing potential as their preferred and usual lifestyle OR
• Use barrier contraception (i.e., male condom with or without spermicide) when having sexual intercourse with a female of childbearing potential who is not currently pregnant.

You may not qualify if:

• Under 18 years of age.
• Known or suspected hypersensitivity or allergic reaction to co-trimoxazole, rezafungin, any echinocandin, or any component of these formulations, including, but not limited to, anaphylaxis or exfoliative skin disorders (e.g., Stevens-Johnson syndrome or toxic epidermal necrolysis).
• Any contraindication to co-trimoxazole or intake of a medication or supplement known to severely interact with co-trimoxazole as detailed in the Summary of Product Characteristics (SmPC) of co-trimoxazole, including, but not limited to, acute porphyria or a history of drug-induced immune thrombocytopaenia with use of trimethoprim and/or sulphonamides.
• Creatinine clearance \<15 mL/min or receiving renal replacement therapy.
• Severe hepatic impairment, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>5 × upper limits of normal (ULN), or total bilirubin \>3 × ULN, or a history of chronic cirrhosis (Child-Pugh score \>9).
• A neutrophil count \<1,000 cells/µL or a platelet count \<50,000 cells/µL.
• Immunosuppressive disease other than HIV / acquired immunodeficiency syndrome (AIDS) (e.g., haematopoietic stem cell transplant, solid organ transplant, or primary immune deficiencies) OR prolonged use of immune-weakening medications:
• Having received corticosteroids equivalent to prednisone ≥20 mg daily for at least 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 chemotherapy within 90 days prior to study entry.
• Previously diagnosed with PCP and having received treatment in the past 6 weeks.
• Receiving therapy for PCP at approved therapeutic doses for \>48 hours before randomisation. Exception: receipt of an anti-PCP drug at prophylactic doses (i.e., lower than approved therapeutic doses).
• Meeting National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 criteria for ataxia, tremors, motor neuropathy, or sensory neuropathy of Grade 2 or higher.
• History of severe ataxia, tremors, or neuropathy or a diagnosis of multiple sclerosis or a movement disorder (including Parkinson's disease and Huntington's disease).
• Planned or ongoing therapy at Screening with a known severe neurotoxic medication or with 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.
• Previous participation in this or any other rezafungin study.

Sponsors & Collaborators

• Mundipharma Research Limited: lead

Study Sites (6)

University of Cape Town

Cape Town, South Africa

RECRUITING

Charlotte Maxeke Johannesburg Academic Hospital

Johannesburg, South Africa

RECRUITING

Helen Joseph Hospital

Johannesburg, South Africa

TERMINATED

Global Clinical Trials - Pretoria

Pretoria, South Africa

RECRUITING

Steve Biko Academic Hospital

Pretoria, South Africa

RECRUITING

Netcare Umhlanga Medical Centre

Umhlanga, South Africa

RECRUITING

Related Publications (1)

• Peghin M, Fishman JA, Grossi PA. Pneumocystis jiroveci: still troublesome to diagnose and treat. Curr Opin Infect Dis. 2025 Oct 18. doi: 10.1097/QCO.0000000000001155. Online ahead of print.

  PMID: 41151592 DERIVED

MeSH Terms

Conditions

Pneumonia, Pneumocystis

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination; Rezafungin

Condition Hierarchy (Ancestors)

Lung Diseases, Fungal; Mycoses; Bacterial Infections and Mycoses; Infections; Pneumocystis Infections; Respiratory Tract Infections; Pneumonia; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Mohit Joshi, MD

  Mundipharma Research Limited

  STUDY DIRECTOR

Central Study Contacts

Elizabeth Chong, MSc

CONTACT

+441223424900; Clinicaltrialsinfo@mundipharma-rd.eu

Terry Nichols

CONTACT

Clinicaltrialsinfo@mundipharma-rd.eu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2023
• First Posted: April 28, 2023
• Study Start: November 14, 2023
• Primary Completion: May 1, 2025
• Study Completion: August 1, 2025
• Last Updated: April 3, 2025

Record last verified: 2025-04

Locations

ZA (6)