search
Back to results

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

Primary Purpose

Candidemia, Mycoses, Fungal Infection

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Rezafungin for Injection
Posaconazole
Fluconazole
Trimethoprim-sulfamethoxazole (TMP/SMX)
Intravenous Placebo
Oral Placebo
Sponsored by
Cidara Therapeutics Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Candidemia focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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.

  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 14 days before randomization, with results available prior to randomization.
  8. Baseline Toxoplasma serologies available within 6 weeks prior to randomization.
  9. Baseline glucose-6-phosphate dehydrogenase (G6PD) deficiency testing with no evidence of G6PD deficiency performed any time prior to randomization.
  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.
  3. Suspected or diagnosed invasive fungal disease (IFD) within 4 weeks of screening.
  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) ≤75% of predicted value, or O2 saturation ≤85% 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 (≥80 picograms [pg]/mL) within 14 days of transplant.
  9. Receipt of previous allogeneic BMT.
  10. Planned receipt of cord blood for transplantation.
  11. Planned peripheral blood or marrow autograft.
  12. Underlying diagnosis of multiple myeloma.
  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 greater to assure more than 5 half-lives have passed to prevent overlapping toxicities when this study's investigational product is dosed, or presence of an investigational device at the time of screening.
  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.
  24. Body weight >130 kilograms (kg) at screening.

Sites / Locations

  • University of Alabama at BirminghamRecruiting
  • UCLA Center for Health SciencesRecruiting
  • Augusta University Medical CenterRecruiting
  • University of ChicagoRecruiting
  • University of Maryland Medical CenterRecruiting
  • Mayo ClinicRecruiting
  • Hackensack University Medical CenterRecruiting
  • Fred Hutchinson Cancer CenterRecruiting
  • AZ Sint-JanRecruiting
  • University Hospitals Leuven, Campus Gasthuisberg - UZ LeuvenRecruiting
  • Hamilton Health Sciences' Juravinski HospitalRecruiting
  • McGill University Health CenterRecruiting
  • Jean Minjoz HospitalRecruiting
  • Henri Mondor HospitalRecruiting
  • Grenoble Alpes University Hospital CenterRecruiting
  • University Hospital of LimogesRecruiting
  • University Hospital of NantesRecruiting
  • Hospital Saint Antoine Ap-HpRecruiting
  • University Hospital of BordeauxRecruiting
  • Lyon-Sud Hospital CenterRecruiting
  • University Hospital Carl Gustav Carus Dresden
  • Essen University Hospital
  • University Hospital of CologneRecruiting
  • Johannes Gutenberg University Medical Center
  • University Hospital MünsterRecruiting
  • San Martino Polyclinic HospitalRecruiting
  • Agostino Gemelli University PoliclinicRecruiting
  • Humanitas Cancer CenterRecruiting
  • University Hospital Vall d'HebronRecruiting
  • Hospital Clinic of Barcelona
  • Hospital de la PrincesaRecruiting
  • University Hospital Ramon y CajalRecruiting
  • Puerta de Hierro Majadahonda University HospitalRecruiting
  • University Hospital of SalamancaRecruiting
  • University Hospital of ValenciaRecruiting
  • La Fe University and Polytechnic HospitalRecruiting
  • University Hospitals GenevaRecruiting
  • Hacettepe University School of MedicineRecruiting
  • Ankara University School of MedicineRecruiting
  • Kings College Hospital NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Group 1: Rezafungin for Injection

Group 2: Oral Antifungal

Arm Description

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.

Subjects in SAR treatment group will receive 400 mg oral fluconazole once daily for 13 weeks. Fluconazole may be switched, due to acute clinically significant graft versus-host disease (GVHD), to 300 mg oral posaconazole twice daily on the first day of the medication switch and 300 mg once daily, thereafter. However, subjects who are switched to posaconazole cannot be switched back to fluconazole. Azole-based antifungal therapy (fluconazole or posaconazole) can be switched from daily oral therapy to daily IV therapy at the discretion of the Investigator. 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.

Outcomes

Primary Outcome Measures

Noninferior Fungal-Free Survival (US FDA)
The number of subjects in each treatment group who are fungal-free and survive.
Noninferior Fungal-Free Survival (US FDA)
The percentage of subjects in each treatment group who are fungal-free and survive.
Superior Fungal-Free Survival (EMA)
The number of subjects in each treatment group who are fungal-free and survive.
Superior Fungal-Free Survival (EMA)
The percentage of subjects in each treatment group who are fungal-free and survive.

Secondary Outcome Measures

Compare Discontinuation for Toxicity or Intolerance
The number of subjects that discontinued Rezafungin for Injection compared to the standard antimicrobial regimen (SAR) secondary to toxicity or intolerance.
Compare Discontinuation for Toxicity or Intolerance
The percentage of subjects that discontinued Rezafungin for Injection compared to the standard antimicrobial regimen (SAR) secondary to toxicity or intolerance.
Compare Proven and Probable IFD
The number of subjects in each treatment group who have proven and probable IFD including the number of invasive infections from Candida spp., Aspergillus spp., and Pneumocystis jirovecii.
Compare Proven and Probable IFD
The percentage of subjects in each treatment group who have proven and probable IFD including the number of invasive infections from Candida spp., Aspergillus spp., and Pneumocystis jirovecii.
Compare Fungal-Free Survival with or without a Diagnosis of Clinically Significant GVHD
The number of subjects in each treatment group who are fungal-free survival with or without a diagnosis of clinically significant GVHD.
Compare Fungal-Free Survival with or without a Diagnosis of Clinically Significant GVHD
The percentage of subjects in each treatment group who are fungal-free survival with or without a diagnosis of clinically significant GVHD.
Compare Time to IFD, or Death
Evaluate time to IFD (proven or probable IFD) or death in subjects randomized to Rezafungin for Injection compared to the standard antimicrobial regimen (SAR).
Compare Mortality
Evaluate overall mortality and attributable mortality, with and without adjustment for patient comorbidity indices, in subjects randomized to Rezafungin for Injection compared to the SAR.
Incidence of Treatment Emergent Adverse Events [Safety and Tolerability]
The number of subjects with incidence of treatment emergent adverse events based on clinical chemistry, hematology and urine analysis laboratory test, vital sign, physical exams and ECG abnormalities.

Full Information

First Posted
April 22, 2020
Last Updated
October 16, 2023
Sponsor
Cidara Therapeutics Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT04368559
Brief Title
Study of Rezafungin Compared to Standard Antimicrobial Regimen for Prevention of Invasive Fungal Diseases in Adults Undergoing Allogeneic Blood and Marrow Transplantation
Acronym
ReSPECT
Official Title
A Phase 3, Multicenter, Randomized, Double-Blind Study of the Efficacy and Safety of Rezafungin for Injection Versus the Standard Antimicrobial Regimen to Prevent Invasive Fungal Diseases in Adults Undergoing Allogeneic Blood and Marrow Transplantation (The ReSPECT Study)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 11, 2020 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cidara Therapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Candidemia, Mycoses, Fungal Infection, Fungemia, Invasive Candidiasis, Pneumocystis, Mold Infection, Invasive Fungal Disease, Prophylaxis of Invasive Fungal Infections, 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

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
462 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1: Rezafungin for Injection
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 2: Oral Antifungal
Arm Type
Active Comparator
Arm Description
Subjects in SAR treatment group will receive 400 mg oral fluconazole once daily for 13 weeks. Fluconazole may be switched, due to acute clinically significant graft versus-host disease (GVHD), to 300 mg oral posaconazole twice daily on the first day of the medication switch and 300 mg once daily, thereafter. However, subjects who are switched to posaconazole cannot be switched back to fluconazole. Azole-based antifungal therapy (fluconazole or posaconazole) can be switched from daily oral therapy to daily IV therapy at the discretion of the Investigator. 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.
Intervention Type
Drug
Intervention Name(s)
Rezafungin for Injection
Other Intervention Name(s)
Intravenous antifungal therapy
Intervention Description
Intravenous antifungal therapy
Intervention Type
Drug
Intervention Name(s)
Posaconazole
Other Intervention Name(s)
Noxafil
Intervention Description
Oral antifungal therapy
Intervention Type
Drug
Intervention Name(s)
Fluconazole
Other Intervention Name(s)
Generic Fluconazole
Intervention Description
Oral antifungal therapy
Intervention Type
Drug
Intervention Name(s)
Trimethoprim-sulfamethoxazole (TMP/SMX)
Other Intervention Name(s)
Bactrim, Septra
Intervention Description
Oral antibacterial therapy
Intervention Type
Drug
Intervention Name(s)
Intravenous Placebo
Other Intervention Name(s)
Placebo Infusion
Intervention Description
Normal saline
Intervention Type
Drug
Intervention Name(s)
Oral Placebo
Other Intervention Name(s)
encapsulated cellulose
Intervention Description
Microcrystalline cellulose
Primary Outcome Measure Information:
Title
Noninferior Fungal-Free Survival (US FDA)
Description
The number of subjects in each treatment group who are fungal-free and survive.
Time Frame
Day 90 (±7 days)
Title
Noninferior Fungal-Free Survival (US FDA)
Description
The percentage of subjects in each treatment group who are fungal-free and survive.
Time Frame
Day 90 (±7 days)
Title
Superior Fungal-Free Survival (EMA)
Description
The number of subjects in each treatment group who are fungal-free and survive.
Time Frame
Day 90 (±7 days)
Title
Superior Fungal-Free Survival (EMA)
Description
The percentage of subjects in each treatment group who are fungal-free and survive.
Time Frame
Day 90 (±7 days)
Secondary Outcome Measure Information:
Title
Compare Discontinuation for Toxicity or Intolerance
Description
The number of subjects that discontinued Rezafungin for Injection compared to the standard antimicrobial regimen (SAR) secondary to toxicity or intolerance.
Time Frame
Day 90 (±7 days)
Title
Compare Discontinuation for Toxicity or Intolerance
Description
The percentage of subjects that discontinued Rezafungin for Injection compared to the standard antimicrobial regimen (SAR) secondary to toxicity or intolerance.
Time Frame
Day 90 (±7 days)
Title
Compare Proven and Probable IFD
Description
The number of subjects in each treatment group who have proven and probable IFD including the number of invasive infections from Candida spp., Aspergillus spp., and Pneumocystis jirovecii.
Time Frame
Day 90 (±7 days)
Title
Compare Proven and Probable IFD
Description
The percentage of subjects in each treatment group who have proven and probable IFD including the number of invasive infections from Candida spp., Aspergillus spp., and Pneumocystis jirovecii.
Time Frame
Day 90 (±7 days)
Title
Compare Fungal-Free Survival with or without a Diagnosis of Clinically Significant GVHD
Description
The number of subjects in each treatment group who are fungal-free survival with or without a diagnosis of clinically significant GVHD.
Time Frame
Day 90 (±7 days)
Title
Compare Fungal-Free Survival with or without a Diagnosis of Clinically Significant GVHD
Description
The percentage of subjects in each treatment group who are fungal-free survival with or without a diagnosis of clinically significant GVHD.
Time Frame
Day 90 (±7 days)
Title
Compare Time to IFD, or Death
Description
Evaluate time to IFD (proven or probable IFD) or death in subjects randomized to Rezafungin for Injection compared to the standard antimicrobial regimen (SAR).
Time Frame
Day 90 (±7 days)
Title
Compare Mortality
Description
Evaluate overall mortality and attributable mortality, with and without adjustment for patient comorbidity indices, in subjects randomized to Rezafungin for Injection compared to the SAR.
Time Frame
Day 1 through follow-up visit (Day 120)
Title
Incidence of Treatment Emergent Adverse Events [Safety and Tolerability]
Description
The number of subjects with incidence of treatment emergent adverse events based on clinical chemistry, hematology and urine analysis laboratory test, vital sign, physical exams and ECG abnormalities.
Time Frame
Day 1 through follow-up visit (Day 120)
Other Pre-specified Outcome Measures:
Title
Comparison of Fungal-Free
Description
The number of subjects in each treatment group who are fungal-free.
Time Frame
Day 14 (±1 day), Day 28 (±1 day), Day 60 (±5 days), and Day 120 (±7 days)
Title
Comparison of Fungal-Free
Description
The percentage of subjects in each treatment group who are fungal-free.
Time Frame
Day 14 (±1 day), Day 28 (±1 day), Day 60 (±5 days), and Day 120 (±7 days)
Title
Comparison of Presence and Severity of GHVD
Description
Evaluate the presence and severity of GVHD in subjects randomized to Rezafungin for Injection compared to the SAR.
Time Frame
Day 90 (±7 days)
Title
Comparison of Fungal-Free with AML
Description
The number of subjects in each treatment group who are fungal-free with an underlying diagnosis of acute myeloid leukemia (AML).
Time Frame
Day 90 (±7 days)
Title
Comparison of Fungal-Free with AML
Description
The percentage of subjects in each treatment group who are fungal-free with an underlying diagnosis of acute myeloid leukemia (AML).
Time Frame
Day 90 (±7 days)
Title
Compare Incidence of IFD
Description
Evaluate the incidence of proven, probable, possible, and presumptive IFD in subjects randomized to Rezafungin for Injection compared to the SAR.
Time Frame
Day 14 (±1 day), Day 28 (±1 day), Day 60 (±5 days), Day 90 (±7 days), and Day 120 (±7 days)
Title
Compare Relapse-Free Survival
Description
Evaluate relapse-free survival, with and without adjustment for patient comorbidity indices, in subjects randomized to Rezafungin for Injection compared to the SAR.
Time Frame
Day 1 through follow-up visit (Day 120)
Title
Evaluate PK (Cmax)
Description
Evaluate maximum plasma concentration (Cmax).
Time Frame
Day 0 (±2 days) within 10 minutes before end of infusion, and one sample between end of infusion and 12 hours after end of infusion; Days 1-4, one sample at any time; Day 7 (±1 day), Day 28 (±1 day), and Day 63 (±1 day) prior to dosing; and EOT visit
Title
Evaluate PK (Tmax)
Description
Evaluate time to Cmax.
Time Frame
Day 0 (±2 days) within 10 minutes before end of infusion, and one sample between end of infusion and 12 hours after end of infusion; Days 1-4, one sample at any time; Day 7 (±1 day), Day 28 (±1 day), and Day 63 (±1 day) prior to dosing; and EOT visit
Title
Evaluate PK (AUC)
Description
Evaluate area under the curve (AUC).
Time Frame
Day 0 (±2 days) within 10 minutes before end of infusion, and one sample between end of infusion and 12 hours after end of infusion; Days 1-4, one sample at any time; Day 7 (±1 day), Day 28 (±1 day), and Day 63 (±1 day) prior to dosing; and EOT visit
Title
Compare Post-Engraftment Cytopenias and Transfusion Requirements
Description
Evaluate post-engraftment cytopenias and transfusion requirements of Rezafungin for Injection compared to the SAR.
Time Frame
Day 1 through follow-up visit (Day 120)
Title
Compare Infections Caused by TMP/SMX-Sensitive Organisms
Description
Evaluate infections caused by TMP/SMX-sensitive organisms (Toxoplasma gondii [T. gondii], Nocardia spp.) in Rezafungin for Injection compared to the SAR.
Time Frame
Day 14 (±1 day), Day 28 (±1 day), Day 60 (±5 days), Day 90 (±7 days), and Day 120 (±7 days)
Title
Compare Antifungal Prophylaxis
Description
Evaluate interruption and discontinuation of antifungal prophylaxis due to suspected IFDs of Rezafungin for Injection compared to the SAR.
Time Frame
Day 14 (±1 day), Day 28 (±1 day), Day 60 (±5 days), Day 90 (±7 days), and Day 120 (±7 days)
Title
Compare the health economics outcome research (HEOR) variable of "Days in Hospital"
Description
Evaluate the number of hospital days for subjects randomized to Rezafungin for Injection compared to the SAR.
Time Frame
Once weekly for outpatient, or twice weekly for inpatient, at completion of study drug therapy [Day 90 (±7 days)] and for 30 days [Day 120 (±7 days)]
Title
Compare the health economics outcome research (HEOR) variable of "Days in Intensive Care Unit (ICU)"
Description
Evaluate the number of days in ICU for subjects randomized to Rezafungin for Injection compared to the SAR.
Time Frame
Once weekly for outpatient, or twice weekly for inpatient, at completion of study drug therapy [Day 90 (±7 days)] and for 30 days [Day 120 (±7 days)]
Title
Compare the health economics outcome research (HEOR) variable of "Readmission due to Infectious Disease Diagnosis"
Description
Evaluate readmission(s) due to infectious disease diagnosis for subjects randomized to Rezafungin for Injection compared to the SAR.
Time Frame
Once weekly for outpatient, or twice weekly for inpatient, at completion of study drug therapy [Day 90 (±7 days)] and for 30 days [Day 120 (±7 days)]
Title
Compare the health economics outcome research (HEOR) variable of "Readmission due to Invasive Fungal Disease Diagnosis"
Description
Evaluate readmission(s) due to invasive fungal disease diagnosis for subjects randomized to Rezafungin for Injection compared to the SAR.
Time Frame
Once weekly for outpatient, or twice weekly for inpatient, at completion of study drug therapy [Day 90 (±7 days)] and for 30 days [Day 120 (±7 days)]
Title
Compare the health economics outcome research (HEOR) variable of "Alternative Antifungal Therapy"
Description
Evaluate the incidence of alternative antifungal therapy compared to Rezafungin for Injection and the SAR.
Time Frame
Once weekly for outpatient, or twice weekly for inpatient, at completion of study drug therapy [Day 90 (±7 days)] and for 30 days [Day 120 (±7 days)]
Title
Compare the health economics outcome research (HEOR) variable of "Antibiotic Therapy"
Description
Evaluate the incidence of antibiotic therapy compared to Rezafungin for Injection and the SAR.
Time Frame
Once weekly for outpatient, or twice weekly for inpatient, at completion of study drug therapy [Day 90 (±7 days)] and for 30 days [Day 120 (±7 days)]

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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). 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 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). Receiving myeloablative or reduced-intensity conditioning regimens. 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: 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). 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. Baseline blood samples drawn for Platelia galactomannan enzyme immunoassay (GM EIA) and β-D glucan levels within 14 days before randomization, with results available prior to randomization. Baseline Toxoplasma serologies available within 6 weeks prior to randomization. Baseline glucose-6-phosphate dehydrogenase (G6PD) deficiency testing with no evidence of G6PD deficiency performed any time prior to randomization. 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: 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 screening. 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) ≤70% 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 14 days of 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. 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. Known hypersensitivity to Rezafungin for Injection, any echinocandin, fluconazole, posaconazole, other azole antifungal, or to any of their excipients. 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. Recent use of an investigational medicinal product within 28 days or greater to assure more than 5 half-lives have passed to prevent overlapping toxicities when this study's investigational product is dosed, or presence of an investigational device at the time of screening. Known infection with HIV. Subjects with unknown HIV status should be tested for HIV antibodies per standard of care. Pregnant or lactating females. The Principal Investigator (PI) determines that the subject should not participate in the study. Considered unlikely to follow up for 90 days after receipt of the BMT due to logistic concerns (i.e., location relative to transplant center). Known liver cirrhosis, diagnosed according to country or Medical Society specific guidelines and documented in the medical records prior to initiating conditioning regimen. Body weight >130 kilograms (kg) at screening.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Taylor Sandison, MD, MPH
Organizational Affiliation
Cidara Therapeutics Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
UCLA Center for Health Sciences
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Augusta University Medical Center
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Fred Hutchinson Cancer Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98108
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
AZ Sint-Jan
City
Brugge
State/Province
West Vlaanderen
ZIP/Postal Code
8000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
University Hospitals Leuven, Campus Gasthuisberg - UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Hamilton Health Sciences' Juravinski Hospital
City
Hamilton
ZIP/Postal Code
L8V1C3
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
McGill University Health Center
City
Montréal
ZIP/Postal Code
H4A3J1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Jean Minjoz Hospital
City
Besançon
ZIP/Postal Code
25030
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Director of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Henri Mondor Hospital
City
Créteil
ZIP/Postal Code
94000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Grenoble Alpes University Hospital Center
City
Grenoble
ZIP/Postal Code
38043
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
University Hospital of Limoges
City
Limoges
ZIP/Postal Code
87042
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Director of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
University Hospital of Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Hospital Saint Antoine Ap-Hp
City
Paris
ZIP/Postal Code
75012
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
University Hospital of Bordeaux
City
Pessac
ZIP/Postal Code
33604
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Lyon-Sud Hospital Center
City
Pierre-Bénite
ZIP/Postal Code
69495
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
University Hospital Carl Gustav Carus Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Individual Site Status
Terminated
Facility Name
Essen University Hospital
City
Essen
ZIP/Postal Code
45147
Country
Germany
Individual Site Status
Withdrawn
Facility Name
University Hospital of Cologne
City
Köln
ZIP/Postal Code
50937
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Director of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Johannes Gutenberg University Medical Center
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Individual Site Status
Terminated
Facility Name
University Hospital Münster
City
Münster
ZIP/Postal Code
48149
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
San Martino Polyclinic Hospital
City
Genova
ZIP/Postal Code
16132
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Agostino Gemelli University Policlinic
City
Rome
ZIP/Postal Code
00168
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Humanitas Cancer Center
City
Rozzano
ZIP/Postal Code
20089
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
University Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Hospital Clinic of Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Individual Site Status
Terminated
Facility Name
Hospital de la Princesa
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
University Hospital Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Puerta de Hierro Majadahonda University Hospital
City
Majadahonda
ZIP/Postal Code
28220
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
University Hospital of Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
University Hospital of Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
La Fe University and Polytechnic Hospital
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
University Hospitals Geneva
City
Geneva
ZIP/Postal Code
1211
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Hacettepe University School of Medicine
City
Ankara
ZIP/Postal Code
06230
Country
Turkey
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Ankara University School of Medicine
City
Ankara
ZIP/Postal Code
06620
Country
Turkey
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Operations
Phone
858-888-7868
Email
clinicaltrialinfo@cidara.com
Facility Name
Kings College Hospital NHS Foundation Trust
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Individual Site Status
Suspended

12. IPD Sharing Statement

Citations:
PubMed Identifier
33438477
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs