Study of Rezafungin Compared to Standard Antimicrobial Regimen for Prevention of Invasive Fungal Diseases in Adults Undergoing Allogeneic Blood and Marrow Transplantation

NCT ID: NCT04368559

Last Updated: 2026-02-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

602 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-11

Study Completion Date

2026-02-28

Brief Summary

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The purpose of this pivotal study is to determine if intravenous Rezafungin is efficacious and safe in the prevention of invasive fungal diseases when compared to the standard antimicrobial regimen.

Detailed Description

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A Phase 3, multicenter, prospective, randomized, double-blind, efficacy and safety study of Rezafungin for injection versus the standard antimicrobial regimen for the prevention of invasive fungal diseases in subjects undergoing allogeneic blood and marrow transplantation.

Conditions

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Candidemia Mycoses Fungal Infection Fungemia Invasive Candidiasis Pneumocystis Mold Infection Invasive Fungal Disease Prophylaxis of Invasive Fungal Infections Aspergillus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group 1: Rezafungin for Injection

Subjects in Rezafungin treatment group will receive a 400 mg loading dose in Week 1, followed by 200 mg once weekly, for a total of 13 weeks. Subjects will receive oral placebo for standard antimicrobial regimen (SAR) azole prophylaxis and oral placebo for SAR anti-Pneumocystis pneumonia (PCP) prophylaxis in accordance with the respective SAR dosing regimens for each. For subjects who are switched to a SAR IV regimen, oral placebo for SAR azole prophylaxis will be changed to IV placebo. There is no IV option for SAR anti-PCP prophylaxis.

Group Type EXPERIMENTAL

Rezafungin for Injection

Intervention Type DRUG

Intravenous antifungal therapy

Intravenous Placebo

Intervention Type DRUG

Normal saline

Oral Placebo

Intervention Type DRUG

Microcrystalline cellulose

Group 2: Oral Antifungal

Subjects randomized to the SAR will receive either fluconazole or posaconazole as the first-line SAR as per site's standard practice. Fluconazole will be administered orally at once daily doses of 400 mg for 13 weeks. Posaconazole will be administered orally as 300 mg twice daily on the first day and 300 mg once daily thereafter for 13 weeks. Azole-based antifungal therapy (fluconazole or posaconazole) can be switched from oral therapy to IV therapy if there is oral intolerance, at the discretion of the Investigator.

Subjects who started on fluconazole SAR may be switched to posaconazole at the discretion of the Investigator if they develop acute clinically significant GVHD; In addition, subjects in the SAR group will receive anti PCP prophylaxis with oral TMP/SMX (80 mg TMP/ 400 mg SMX) once daily. There is no IV option for SAR anti-PCP prophylaxis.

Group Type ACTIVE_COMPARATOR

Posaconazole

Intervention Type DRUG

Oral antifungal therapy

Fluconazole

Intervention Type DRUG

Oral antifungal therapy

Trimethoprim-sulfamethoxazole (TMP/SMX)

Intervention Type DRUG

Oral antibacterial therapy

Interventions

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Rezafungin for Injection

Intravenous antifungal therapy

Intervention Type DRUG

Posaconazole

Oral antifungal therapy

Intervention Type DRUG

Fluconazole

Oral antifungal therapy

Intervention Type DRUG

Trimethoprim-sulfamethoxazole (TMP/SMX)

Oral antibacterial therapy

Intervention Type DRUG

Intravenous Placebo

Normal saline

Intervention Type DRUG

Oral Placebo

Microcrystalline cellulose

Intervention Type DRUG

Other Intervention Names

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Intravenous antifungal therapy Noxafil Generic Fluconazole Bactrim Septra Placebo Infusion encapsulated cellulose

Eligibility Criteria

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Inclusion Criteria

1. Willing and able to provide written informed consent.
2. Males or females ≥18 years of age.
3. Receiving a human leukocyte antigen (HLA) matched allogeneic peripheral BMT from a family or unrelated donor, HLA-mismatched related or unrelated donor, or haploidentical donor.
4. Diagnosed with 1 of the following underlying diseases:

1. Acute myeloid leukemia (AML), with or without a history of myelodysplastic syndrome, in first or second complete remission.
2. Acute lymphoblastic leukemia, in first or second complete remission.
3. Acute undifferentiated leukemia in first or second remission.
4. Acute biphenotypic leukemia in first or second complete remission.
5. Chronic myelogenous leukemia in either chronic or accelerated phase.
6. One of the following myelodysplastic syndrome(s) defined by the following:

i. Refractory anemia.

ii. Refractory anemia with ringed sideroblasts.

iii. Refractory cytopenia with multilineage dysplasia.

iv. Refractory cytopenia with multilineage dysplasia and ringed sideroblasts.

v. Refractory anemia with excess blasts - 1 (5-10% blasts).

vi. Refractory anemia with excess blasts - 2 (10-20% blasts).

vii. Myelodysplastic syndrome, unclassified.

viii. Myelodysplastic syndrome associated with isolated del (5q).

g. Lymphoma (including Hodgkin's) with chemosensitive disease (i.e., response to chemotherapy) and receiving a related or unrelated donor transplant.

h. Aplastic anemia.

i. Primary or secondary myelofibrosis.

j. Chronic myelomonocytic leukemia.

k. Chronic lymphocytic leukemia.

l. Drepanocytosis (sickle cell anemia).

m. Red blood cell aplasia.

n. Myeloproliferative disorder, unclassified.

o. Multiple myeloma (plasma cell myeloma).
5. Receiving myeloablative or reduced-intensity conditioning regimens.
6. Adequate renal and hepatic function prior to initiation of conditioning regimen, therefore between 40 days prior and 10 days prior to BMT, documented as follows:

1. Hepatic: alanine aminotransferase less than or equal to (≤) 2.5 × upper limit of normal (ULN) and total serum bilirubin ≤1.5 × ULN (excluding Gilbert's Syndrome).
2. Renal: serum creatinine ≤2 milligrams (mg)/deciliter (dL) and with creatinine clearance (CrCl) greater than or equal to (≥) 30 milliliters (mL)/minute (min) without a history of renal transplant, or undergoing weekly dialysis within 4 weeks of the BMT.
7. Baseline blood samples drawn for Platelia galactomannan enzyme immunoassay (GM EIA) and β-D glucan levels within 15 days before randomization, with results available prior to randomization.
8. Baseline Toxoplasma serologies available within 6 weeks prior to randomization. Subjects with a positive toxoplasma IgG serology at any time prior to randomization do not need to repeat the toxoplasma serologies (IgG and IgM) and will be considered to have a prior history of toxoplasmosis.
9. Baseline glucose-6-phosphate dehydrogenase (G6PD) deficiency determination by the investigator prior to randomization with no known evidence of G6PD deficiency performed any time prior to randomization. If the Investigator assesses the subject as G6PD sufficient, the G6PD test result does not need to be entered into the EDC system.
10. Female subjects of child-bearing potential \<2 years post-menopausal (unless surgically sterile) must agree to and comply with using 1 barrier method (e.g., female condom with spermicide) plus one other highly effective method of birth control (e.g., oral contraceptive, implant, injectable, indwelling intrauterine device, vasectomized partner), or sexual abstinence (only possible if it corresponds to the subject's usual lifestyle) while participating in this study, and for 30 days after the last dose of study drug. Male subjects must be vasectomized, abstain from sexual intercourse, or agree to use barrier contraception (condom with spermicide), and agree not to donate sperm while participating in the study and for 120 days from the last IV dose of study drug.

Exclusion Criteria

1. Diagnosis of AML not in morphological remission.
2. Diagnosis of chemotherapy-resistant lymphoma: a first relapse can occur provided that a second complete remission has occurred.
3. Suspected or diagnosed invasive fungal disease (IFD) within 4 weeks of randomisation.
4. Diagnosed symptomatic heart failure with left ventricular ejection fraction (LVEF) at rest ≤50%, or shortening fraction ≤26%.
5. Personal or family history of Long QT interval on electrocardiogram (ECG) (QT) syndrome or a prolonged QT interval corrected for heart rate by Fridericia's formula (QTcF) (\>470 milliseconds \[msec\] in males and \>480 msec in females); or concurrent administration of terfenadine, cisapride, astemizole, erythromycin, pimozide, quinidine, or halofantrine.
6. Diagnosed reduced lung function with either diffusion capacity (corrected for hemoglobin) or forced expiratory volume in 1 second (FEV1) ≤65% of predicted value, or O2 saturation ≤82% on room air.
7. Suspected or documented PCP within 2 years of screening.
8. Positive baseline serum Platelia GM EIA (≥ 0.5) and/or β-D glucan assay (Fungitell ≥80 picograms \[pg\]/mL or Fujifilm Wako \>11 pg/mL) within 15 days prior to the transplant.
9. Receipt of previous allogeneic BMT.
10. Planned receipt of cord blood for transplantation.
11. Planned peripheral blood or marrow autograft.
12. Not applicable to protocol Amendment 6.
13. Grade 2 or higher ataxia, tremor, motor neuropathy, or sensory neuropathy, per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
14. History of severe (Grade ≥3) ataxia, neuropathy or tremors; or a diagnosis of multiple sclerosis or a movement disorder (including Parkinson's disease or Huntington's disease).
15. . .

1. Planned or ongoing intake at screening of a known severe neurotoxic medication or with a known moderate neurotoxic medication in a patient with ataxia, tremor, motor neuropathy, or sensory neuropathy of CTCAE version 5.0 Grade 1 or higher.
2. Any contraindication or a medication or supplement known to severely interact with the standard antimicrobial regimen (SAR) as detailed in the US Prescribing Information (USPI) or Summary of Product Characteristics (SmPC) of fluconazole, posaconazole, or TMP/SMX.
16. Known hypersensitivity to Rezafungin for Injection, any echinocandin, fluconazole, posaconazole, other azole antifungal, or to any of their excipients.
17. Known hypersensitivity or inability to receive TMP/SMX or any of its excipients, including but not limited to anaphylaxis, exfoliative skin disorders, or acute porphyria.
18. Recent use of an investigational medicinal product within 28 days or 5 half-lives of the investigational medicinal product, whichever is greater, to prevent overlapping toxicities when this study's investigational product is dosed, or presence of an investigational device at the time of screening. In some cases, use of investigational products may be acceptable in consultation with the Sponsor's Medical Monitor.
19. Known infection with HIV. Subjects with unknown HIV status should be tested for HIV antibodies per standard of care.
20. Pregnant or lactating females.
21. The Principal Investigator (PI) determines that the subject should not participate in the study.
22. Considered unlikely to follow up for 90 days after receipt of the BMT due to logistic concerns (i.e., location relative to transplant center).
23. Known liver cirrhosis, diagnosed according to country or Medical Society specific guidelines and documented in the medical records prior to initiating conditioning regimen.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mundipharma Research Limited

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Laura Cox, PhD

Role: STUDY_DIRECTOR

Mundipharma Research Limited

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

UCLA Center for Health Sciences

Los Angeles, California, United States

Site Status

Stanford University School of Medicine

Stanford, California, United States

Site Status

Augusta University Medical Center

Augusta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

John Hopkins

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Minnesota Physicians

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Mary Hitchcock Memorial Hospital Dartmouth-Hitchcock

Lebanon, New Hampshire, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Stony Brook University Hospital

Stony Brook, New York, United States

Site Status

The University of Oklahoma College of Medicine

Oklahoma City, Oklahoma, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

VCU Medical Center Main Hospital

Richmond, Virginia, United States

Site Status

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status

AZ Sint-Jan

Bruges, West Vlaanderen, Belgium

Site Status

University Hospitals Leuven, Campus Gasthuisberg - UZ Leuven

Leuven, , Belgium

Site Status

Hamilton Health Sciences' Juravinski Hospital

Hamilton, , Canada

Site Status

McGill University Health Center

Montreal, , Canada

Site Status

Jean Minjoz Hospital

Besançon, , France

Site Status

Henri Mondor Hospital

Créteil, , France

Site Status

Grenoble Alpes University Hospital Center

Grenoble, , France

Site Status

University Hospital of Limoges

Limoges, , France

Site Status

University Hospital of Nantes

Nantes, , France

Site Status

Hospital Saint Antoine Ap-Hp

Paris, , France

Site Status

University Hospital of Bordeaux

Pessac, , France

Site Status

Lyon-Sud Hospital Center

Pierre-Bénite, , France

Site Status

University Hospital of Cologne

Cologne, , Germany

Site Status

University Hospital Carl Gustav Carus Dresden

Dresden, , Germany

Site Status

Johannes Gutenberg University Medical Center

Mainz, , Germany

Site Status

University Hospital Münster

Münster, , Germany

Site Status

University Hospital Wurzburg UKW

Würzburg, , Germany

Site Status

San Martino Polyclinic Hospital

Genova, , Italy

Site Status

IEO Istituto Europeo di Oncologia

Milan, , Italy

Site Status

Agostino Gemelli University Policlinic

Rome, , Italy

Site Status

Humanitas Cancer Center

Rozzano, , Italy

Site Status

University Hospital Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Clinic of Barcelona

Barcelona, , Spain

Site Status

University Hospital Ramon y Cajal

Madrid, , Spain

Site Status

Puerta de Hierro Majadahonda University Hospital

Majadahonda, , Spain

Site Status

University Hospital of Salamanca

Salamanca, , Spain

Site Status

University Hospital Marques de Valdecilla

Santander, , Spain

Site Status

University Hospital of Valencia

Valencia, , Spain

Site Status

La Fe University and Polytechnic Hospital

Valencia, , Spain

Site Status

University Hospitals Geneva

Geneva, , Switzerland

Site Status

Addenbrookes Hospital

Cambridge, , United Kingdom

Site Status

University Hospital of Wales

Cardiff, , United Kingdom

Site Status

Kings College Hospital NHS Foundation Trust

London, , United Kingdom

Site Status

St. George's University Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

The Royal Marsden Nhs Foundation Trust

London, , United Kingdom

Site Status

Countries

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United States Belgium Canada France Germany Italy Spain Switzerland United Kingdom

References

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Cross SJ, Wolf J, Patel PA. Prevention, Diagnosis and Management of Pneumocystis jirovecii Infection in Children With Cancer or Receiving Hematopoietic Cell Therapy. Pediatr Infect Dis J. 2023 Dec 1;42(12):e479-e482. doi: 10.1097/INF.0000000000004102. Epub 2023 Sep 21. No abstract available.

Reference Type DERIVED
PMID: 37773627 (View on PubMed)

Ham YY, Lewis JS 2nd, Thompson GR 3rd. Rezafungin: a novel antifungal for the treatment of invasive candidiasis. Future Microbiol. 2021 Jan;16(1):27-36. doi: 10.2217/fmb-2020-0217.

Reference Type DERIVED
PMID: 33438477 (View on PubMed)

Other Identifiers

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2017-004981-85

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CD101.IV.3.08

Identifier Type: -

Identifier Source: org_study_id

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