Clinical trial NCT03667690: Study of Rezafungin Compared to Caspofungin in Subjects With Candidemia and/or Invasive Candidiasis
Official title: A Phase 3, Multicenter, Randomized, Double-blind Study of the Efficacy and Safety of Rezafungin for Injection vs. Intravenous Caspofungin Followed by Oral Fluconazole Step Down in the Treatment of Subjects With Candidemia and/or Invasive Candidiasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Candidemia
Mycoses
Fungal Infection
Invasive Candidiases
Keywords: Mycoses
Candidiasis
Candidiasis, Invasive
Candidemia
Fungemia
Sepsis
Invasive Fungal Infections
Systemic Inflammatory Response Syndrome
Pathologic Processes
Fluconazole
Caspofungin
Echinocandins
Antifungal Agents
Anti-infective 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
Lead sponsor: Cidara Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2018-09-12
Enrollment: 199
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this pivotal study is to determine if intravenous Rezafungin is efficacious and safe in the treatment of candidemia and/or invasive candidiasis when compared to caspofungin (followed by optional oral fluconazole).

Detailed description: A Phase 3, multicenter, prospective, randomized, double-blind, efficacy and safety study of Rezafungin for Injection versus an active comparator regimen of caspofungin followed by optional oral fluconazole step-down therapy in subjects with candidemia and/or invasive candidiasis.

Eligibility criteria: Inclusion Criteria:

1. Willing and able to provide written informed consent. If the subject is unable to consent for himself/herself, a legally acceptable representative must provide informed consent on his/her behalf.
2. Males or females ≥18 years of age.
3. Established mycological diagnosis of candidemia and/or invasive candidiasis from a sample taken ≤4 days (96 hours) before randomization defined as

   * ≥1 blood culture positive for yeast or Candida OR
   * Positive test for Candida from a Sponsor-approved rapid in vitro diagnostic (IVD) OR
   * Positive gram stain (or other method of direct microscopy) for yeast or positive culture for Candida spp. from a specimen obtained from a normally sterile site.
4. Presence of one or more systemic signs attributable to candidemia or invasive candidiasis appearing from ≤12 hours prior to the qualifying positive culture through time of randomization.
5. Willing to initiate or continue medical treatment to cure infections, including receipt of antibiotics and surgical procedures, if required.
6. Female subjects of childbearing potential (all female subjects between 18 years \<2 years post-menopausal unless surgically sterile) must agree to and comply with using one barrier method (e.g., female condom with spermicide) plus one other highly effective method of birth control, or sexual abstinence while participating in this study. Male subjects must be vasectomized, abstain from sexual intercourse, or agree to use barrier contraception, and also agree not to donate sperm while participating in the study and for 90 days thereafter (and at least 120 days from the last dose of study drug).
7. For Candidemia only subjects, drawing of a set of blood cultures within 12 hours prior to randomization in the study. The result of these blood cultures is not required for inclusion in the study.

Exclusion Criteria:

1. Any of the following forms of invasive candidiasis at baseline:

   1. Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed)
   2. Osteomyelitis
   3. Endocarditis or myocarditis
   4. Meningitis, endophthalmitis, chorioretinitis, or any central nervous system infection
   5. Chronic disseminated candidiasis
   6. Urinary tract candidiasis due to ascending Candida infection secondary to obstruction or surgical instrumentation of the urinary tract
2. Received systemic treatment with an antifungal agent at approved doses for treatment of candidemia for \>48 hours (e.g., \>2 doses of a once daily antifungal agent or \>4 doses of a twice daily antifungal agent) ≤4 days (96 hours) before randomization

   a. Exception: Receipt of antifungal therapy to which any Candida spp. isolated in culture is not susceptible
3. Alanine aminotransferase or aspartate aminotransferase levels \>10-fold the upper limit of normal
4. Severe hepatic impairment in subjects with a history of chronic cirrhosis (Child-Pugh score \>9)
5. Presence of an indwelling vascular catheter or device that cannot be removed or an abscess that cannot be drained and is likely to be the source of candidemia or invasive candidiasis
6. Known hypersensitivity to Rezafungin for Injection, caspofungin, any echinocandin, or to any of their excipients
7. Meets National Cancer Institute Common Terminology Criteria for Adverse Events, version 5, criteria for ataxia, tremor, motor neuropathy, or sensory neuropathy of Grade 2 or higher
8. History of severe ataxia, tremor, or neuropathy or a diagnosis of multiple sclerosis or a movement disorder (including Parkinson's Disease or Huntington's Disease)
9. Planned or ongoing therapy at Screening with a known neurotoxic medication
10. Previous participation in this or any previous rezafungin study
11. Current participation in another interventional treatment trial with an investigational agent
12. Recent use of an investigational medicinal product within 28 days of the first dose of study drug or presence of an investigational device at the time of screening.
13. Pregnant or lactating females
14. The Principal Investigator (PI) is of the opinion the subject should not participate in the study

Primary outcomes:
measure: All-Cause Mortality (US FDA Only)
timeFrame: Day 30 (-2 days)
measure: Global Response as Assessed by Data Review Committee (EU European Medicines Agency [EMA] Only)
timeFrame: Day 14 (±1 day)
Secondary outcomes:
measure: Global Response as Assessed by Data Review Committee (US FDA Only)
timeFrame: Day 14 (±1 day)
measure: All-Cause Mortality (EU EMA Only)
timeFrame: Day 30 (-2 days)
measure: Comparison of Global Response (as Assessed by the DRC) by Visit
timeFrame: Day 5, Day 30 (-2 days), End of Treatment (EOT) (≤2 days of last dose) and Follow-up (Days 52-59)
measure: Comparison of Mycological Eradication by Visit
timeFrame: Day 5, Day 14 (±1 day), Day 30 (-2 days), End of Treatment (EOT) (≤2 days of last dose), and Follow-up (Days 52-59)
measure: Comparison of Investigators' Assessment of Clinical Response by Visit
timeFrame: Day 5, Day 14 (±1 day), Day 30 (-2 days), End of Treatment (EOT) (≤2 days of last dose), and Follow-up (Days 52-59)
measure: Comparison of Radiological Response by Investigator by Visit
timeFrame: Day 5, Day 14 (±1 day), Day 30 (-2 days), End of Treatment (EOT) (≤2 days of last dose), and Follow-up (Days 52-59)
measure: Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: Day 1 through Follow-up Visit (Days 52-59)
measure: Evaluate Pharmacokinetics (Cmax)
timeFrame: Day 1, 10 minutes before the end of infusion
measure: Evaluate Pharmacokinetics (Cmin)
timeFrame: Day 8, pre-dose, within 30 minutes prior to the start of infusion
measure: Evaluate Pharmacokinetics (Cmin)
timeFrame: Day 15, pre-dose, within 30 minutes prior to the start of infusion
measure: Evaluate Pharmacokinetics (Cmin)
timeFrame: Day 22, pre-dose, within 30 minutes prior to the start of infusion
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Sacramento
country: United States
facility: UC Davis
state: California
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Hospital-Rochester
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University St. Louis
state: Missouri
city: Butte
country: United States
facility: Mecury Street Medical
state: Montana
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Toledo
country: United States
facility: ID Clinical Research, Ltd.
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Falk Medical Center
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital and Medical Center
state: Pennsylvania
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
city: Temple
country: United States
facility: Baylor Scott and White Medical Center
state: Texas
city: Roanoke
country: United States
facility: Carilion Clinic
state: Virginia
city: Buenos Aires
country: Argentina
facility: Alexander Fleming Specialized Medical Institute
city: Córdoba
country: Argentina
facility: Cordoba Private Hospital
city: Córdoba
country: Argentina
facility: Allende Sanatorium
city: Córdoba
country: Argentina
facility: Mayo Private Sanatorium
city: Mendoza
country: Argentina
facility: Italian Hospital of Mendoza
city: Northmead
country: Australia
facility: Westmead Public Hospital
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital (RMH)
state: Victoria
city: Brussels
country: Belgium
facility: Brugmann University Hospital Center
city: Brussels
country: Belgium
facility: Erasme Hospital
city: Brussels
country: Belgium
facility: University Hospital Brussels
city: Brussels
country: Belgium
facility: Saint Luc University Hospital
city: Leuven
country: Belgium
facility: University Hospitals Leuven, Campus Gasthuisberg
city: Blagoevgrad
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Puls
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment and Emergency Medicine N.I. Pirogov EAD, Sofia, Clinic of Purulent-Septic Surgery
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment and Emergency Medicine N.I. Pirogov EAD
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: The Second People's Hospital of Hefei
state: Anhui
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Chongqing
country: China
facility: Chongqing People's Hospital
state: Chongqing
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Qingyuan
country: China
facility: Qingyuan People's Hospital
state: Guangdong
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
city: Zibo
country: China
facility: Zibo Central Hospital
state: Shandong
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Shanghai
country: China
facility: Huashan Hospital Affiliated Fudan University
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: Tianjin
country: China
facility: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
city: Tianjin
country: China
facility: General Hospital of Tianjin Medical University
city: Armenia
country: Colombia
facility: CEQUIN Foundation Cardiomet
city: Barranquilla
country: Colombia
facility: De La Costa Clinic Ltd.
city: Medellín
country: Colombia
facility: University IPS - Leon XIII Clinic
city: Amiens
country: France
facility: Amiens Picardie University Hospital - South
city: Argenteuil
country: France
facility: Centre Hospitalier Victor Dupouy - Argenteuil
city: Lille
country: France
facility: Roger Salengro Hospital
city: Marseille
country: France
facility: Marseille University Hospital Center - North Hospital
city: Nantes
country: France
facility: Hotel Dieu Hospital Nantes University Hospital Center
city: Paris
country: France
facility: Saint-Louis Hospital
city: Paris
country: France
facility: Paris University Hospitals Center - Cochin Hospital
city: Poitiers
country: France
facility: University Hospital Center of Poitiers
city: Strasbourg
country: France
facility: Civil Hospital of Strasbourg
city: Tours
country: France
facility: Tours University Hospital Center, Bretonneau Hospital
city: Cologne
country: Germany
facility: University Hospital Köln
city: Freiburg
country: Germany
facility: University Hospital Freiburg
city: Mainz
country: Germany
facility: Johannes Gutenberg University Medical Center
city: Athens
country: Greece
facility: General Hospital of Athens "Evangelismos", 5th Department of Internal Medicine and Infectious Diseases Unit
city: Athens
country: Greece
facility: General Hospital of Athens "Evangelismos"
city: Athens
country: Greece
facility: General Hospital of Athens "Laikon", Infectious Diseases Unit
city: Athens
country: Greece
facility: General Hospital of Athens "Laikon"
city: Thessaloníki
country: Greece
facility: General Hospital of Thessaloniki Ippokratio
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: H̱olon
country: Israel
facility: Edith Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Nazareth
country: Israel
facility: The Baruch Padeh Medical Center
city: Safed
country: Israel
facility: Ziv Medical Center
city: Tel Aviv
country: Israel
facility: The Tel Aviv Sourasky Medical Center
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Bologna
country: Italy
facility: Polyclinic S. Orsola-Malpighi, Dept. of Organ Impairment and Transplants
city: Milan
country: Italy
facility: ASST Large Metropolitan Hospital Niguarda, Infectious Diseases Department
city: Modena
country: Italy
facility: University Polyclinic Hospital of Modena
city: Modena
country: Italy
facility: University Hospital of Modena
city: Monza
country: Italy
facility: University of Milano-Bicocca - San Gerardo Hospital
city: Palermo
country: Italy
facility: University Polyclinic Hospital "Paolo Giaccone" Palermo, Infectious Disease Department, ICU
city: Rome
country: Italy
facility: University Polyclinic Foundation Agostino Gemelli - IRCCS
city: Trieste
country: Italy
facility: Integrated University Health Authority of Trieste
city: Udine
country: Italy
facility: Integrated University Hospital "Santa Maria della Misericordia" of Udine
city: Wŏnju
country: Korea, Republic of
facility: Wonju Severance Christian Hospital
state: Gangwon-do
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Badalona
country: Spain
facility: University Hospital Germans Trias i Pujol
city: Baracaldo
country: Spain
facility: University Hospital Cruces
city: Barcelona
country: Spain
facility: Hospital del Mar, Department of Infectious Diseases
city: Barcelona
country: Spain
facility: University Hospital Vall d'Hebron (HUVH)
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
city: Barcelona
country: Spain
facility: Parc Tauli Health Corporation
city: Madrid
country: Spain
facility: General University Hospital Gregorio Maranon
city: Madrid
country: Spain
facility: University Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: University Hospital Clinical San Carlos
city: Madrid
country: Spain
facility: La Paz University Hospital
city: Majadahonda
country: Spain
facility: University Hospital Puerta de Hierro Majadahonda
city: Sevilla
country: Spain
facility: University Hospital Virgen Macarena
city: Valencia
country: Spain
facility: University and Polytechnic Hospital La Fe
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Bangkok
country: Thailand
facility: Rajavithi Hospital
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital
city: Pathum Thani
country: Thailand
facility: Thammasat University Hospital
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital
city: Ankara
country: Turkey
facility: Hacettepe University School of Medicine
city: Ankara
country: Turkey
facility: Ankara University School of Medicine
city: Istanbul
country: Turkey
facility: Istanbul University School of Medicine
city: Istanbul
country: Turkey
facility: Marmara University Pendik Training and Research Hospital
city: Istanbul
country: Turkey
facility: Medipol Mega University Hospital
Study officials:
affiliation: Cidara Therapeutics Inc.
name: Taylor Sandison, MD, MPH
role: STUDY_DIRECTOR
References:
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.