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

NCT04368559 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: CD101.IV.3.082017-004981-85
• Study Type: interventional
• Target: 602
• Locations: 9 countries
• Sites: 53

Brief Summary

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.

Conditions

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

Keywords

Mycoses; Prophylaxis of Invasive Fungal Infections; Aspergillus; Candidiasis; Candidemia; Candidiasis, Invasive; Fungemia; Sepsis; Blood and Marrow Transplant (BMT); Infection; Invasive Fungal Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Fluconazole; Posaconazole; Caspofungin; Trimethoprim-sulfamethoxazole (TMP/SMX); Echinocandins; Antifungal Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Physiological Effects of Drugs; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Pneumocystis; Mold Infection; Rezafungin; Anti-Infective Agents

Outcome Measures

Primary Outcomes (4)

• Noninferior Fungal-Free Survival (US FDA)

  The number of subjects in each treatment group who are fungal-free and survive.

  Day 90 (±7 days)

• Noninferior Fungal-Free Survival (US FDA)

  The percentage of subjects in each treatment group who are fungal-free and survive.

  Day 90 (±7 days)

• Superior Fungal-Free Survival (EMA)

  The number of subjects in each treatment group who are fungal-free and survive.

  Day 90 (±7 days)

• Superior Fungal-Free Survival (EMA)

  The percentage of subjects in each treatment group who are fungal-free and survive.

  Day 90 (±7 days)

Secondary Outcomes (9)

• Compare Discontinuation for Toxicity or Intolerance

  Day 90 (±7 days)

• Compare Discontinuation for Toxicity or Intolerance

  Day 90 (±7 days)

• Compare Proven and Probable IFD

  Day 90 (±7 days)

• Compare Proven and Probable IFD

  Day 90 (±7 days)

• Compare Fungal-Free Survival with or without a Diagnosis of Clinically Significant GVHD

  Day 90 (±7 days)

Other Outcomes (19)

• Comparison of Fungal-Free

  Day 14 (±1 day), Day 28 (±1 day), Day 60 (±5 days), and Day 120 (±7 days)

• Comparison of Fungal-Free

  Day 14 (±1 day), Day 28 (±1 day), Day 60 (±5 days), and Day 120 (±7 days)

• Comparison of Presence and Severity of GHVD

  Day 90 (±7 days)

Study Arms (2)

Group 1: Rezafungin for Injection

EXPERIMENTAL

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.

Drug: Rezafungin for Injection; Drug: Intravenous Placebo; Drug: Oral Placebo

Group 2: Oral Antifungal

ACTIVE COMPARATOR

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.

Drug: Posaconazole; Drug: Fluconazole; Drug: Trimethoprim-sulfamethoxazole (TMP/SMX)

Interventions

Rezafungin for Injection DRUG

Intravenous antifungal therapy

Also known as: Intravenous antifungal therapy

Group 1: Rezafungin for Injection

Posaconazole DRUG

Oral antifungal therapy

Also known as: Noxafil

Group 2: Oral Antifungal

Fluconazole DRUG

Oral antifungal therapy

Also known as: Generic Fluconazole

Group 2: Oral Antifungal

Trimethoprim-sulfamethoxazole (TMP/SMX) DRUG

Oral antibacterial therapy

Also known as: Bactrim, Septra

Group 2: Oral Antifungal

Intravenous Placebo DRUG

Normal saline

Also known as: Placebo Infusion

Group 1: Rezafungin for Injection

Oral Placebo DRUG

Microcrystalline cellulose

Also known as: encapsulated cellulose

Group 1: Rezafungin for Injection

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent.
• Males or females ≥18 years of age.
• 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.
• Diagnosed with 1 of the following underlying diseases:
• Acute myeloid leukemia (AML), with or without a history of myelodysplastic syndrome, in first or second complete remission.
• Acute lymphoblastic leukemia, in first or second complete remission.
• Acute undifferentiated leukemia in first or second remission.
• Acute biphenotypic leukemia in first or second complete remission.
• Chronic myelogenous leukemia in either chronic or accelerated phase.
• 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).

You may not qualify if:

• Diagnosis of AML not in morphological remission.
• Diagnosis of chemotherapy-resistant lymphoma: a first relapse can occur provided that a second complete remission has occurred.
• Suspected or diagnosed invasive fungal disease (IFD) within 4 weeks of randomisation.
• Diagnosed symptomatic heart failure with left ventricular ejection fraction (LVEF) at rest ≤50%, or shortening fraction ≤26%.
• 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.
• 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.
• Suspected or documented PCP within 2 years of screening.
• 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.
• Receipt of previous allogeneic BMT.
• Planned receipt of cord blood for transplantation.
• Planned peripheral blood or marrow autograft.
• Not applicable to protocol Amendment 6.
• 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.
• 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).
• 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.

Sponsors & Collaborators

• Mundipharma Research Limited: lead

Study Sites (53)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

UCLA Center for Health Sciences

Los Angeles, California, 90095, United States

Location

Stanford University School of Medicine

Stanford, California, 94304, United States

Location

Augusta University Medical Center

Augusta, Georgia, 30912, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

John Hopkins

Baltimore, Maryland, 21218, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Minnesota Physicians

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Mary Hitchcock Memorial Hospital Dartmouth-Hitchcock

Lebanon, New Hampshire, 03756, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

The University of Oklahoma College of Medicine

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

VCU Medical Center Main Hospital

Richmond, Virginia, 23219, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98108, United States

Location

AZ Sint-Jan

Bruges, West Vlaanderen, 8000, Belgium

Location

University Hospitals Leuven, Campus Gasthuisberg - UZ Leuven

Leuven, 3000, Belgium

Location

Hamilton Health Sciences' Juravinski Hospital

Hamilton, L8V1C3, Canada

Location

McGill University Health Center

Montreal, H4A3J1, Canada

Location

Jean Minjoz Hospital

Besançon, 25030, France

Location

Henri Mondor Hospital

Créteil, 94000, France

Location

Grenoble Alpes University Hospital Center

Grenoble, 38043, France

Location

University Hospital of Limoges

Limoges, 87042, France

Location

University Hospital of Nantes

Nantes, 44093, France

Location

Hospital Saint Antoine Ap-Hp

Paris, 75012, France

Location

University Hospital of Bordeaux

Pessac, 33604, France

Location

Lyon-Sud Hospital Center

Pierre-Bénite, 69495, France

Location

University Hospital of Cologne

Cologne, 50937, Germany

Location

University Hospital Carl Gustav Carus Dresden

Dresden, 01307, Germany

Location

Johannes Gutenberg University Medical Center

Mainz, 55131, Germany

Location

University Hospital Münster

Münster, 48149, Germany

Location

University Hospital Wurzburg UKW

Würzburg, 97080, Germany

Location

San Martino Polyclinic Hospital

Genova, 16132, Italy

Location

IEO Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Agostino Gemelli University Policlinic

Rome, 00168, Italy

Location

Humanitas Cancer Center

Rozzano, 20089, Italy

Location

University Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic of Barcelona

Barcelona, 08036, Spain

Location

University Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Puerta de Hierro Majadahonda University Hospital

Majadahonda, 28220, Spain

Location

University Hospital of Salamanca

Salamanca, 37007, Spain

Location

University Hospital Marques de Valdecilla

Santander, 39008, Spain

Location

University Hospital of Valencia

Valencia, 46010, Spain

Location

La Fe University and Polytechnic Hospital

Valencia, 46026, Spain

Location

University Hospitals Geneva

Geneva, 1211, Switzerland

Location

Addenbrookes Hospital

Cambridge, cb2 0QQ, United Kingdom

Location

University Hospital of Wales

Cardiff, CF144XW, United Kingdom

Location

Kings College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

St. George's University Hospitals NHS Foundation Trust

London, SW17 0QT, United Kingdom

Location

The Royal Marsden Nhs Foundation Trust

London, SW3 6JJ, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 37773627 DERIVED

• 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.

  PMID: 33438477 DERIVED

MeSH Terms

Conditions

Candidemia; Mycoses; Fungemia; Candidiasis, Invasive; Pneumonia, Pneumocystis; Invasive Fungal Infections; Candidiasis; Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes

Interventions

Rezafungin; Injections; posaconazole; Fluconazole; Trimethoprim, Sulfamethoxazole Drug Combination

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Pathological Conditions, Signs and Symptoms; Lung Diseases, Fungal; Pneumocystis Infections; Respiratory Tract Infections; Pneumonia; Lung Diseases; Respiratory Tract Diseases; Shock

Intervention Hierarchy (Ancestors)

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

Study Officials

• Laura Cox, PhD

  Mundipharma Research Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2020
• First Posted: April 30, 2020
• Study Start: May 11, 2020
• Primary Completion: January 29, 2026
• Study Completion: January 29, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (18); BE (2); ES (8); CH (1); IT (4); FR (8); CA (2); GB (5); DE (5)