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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03667690
Other study ID # CD101.IV.3.05
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date October 7, 2018
Est. completion date October 7, 2021

Study information

Verified date December 2022
Source Cidara Therapeutics Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


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.


Recruitment information / eligibility

Status Completed
Enrollment 199
Est. completion date October 7, 2021
Est. primary completion date October 7, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

Drug:
Rezafungin for Injection
Intravenous antifungal therapy
Caspofungin
Intravenous antifungal therapy
Fluconazole
Oral antifungal therapy
intravenous placebo
Normal saline
oral placebo
Microcrystalline cellulose

Locations

Country Name City State
Argentina Alexander Fleming Specialized Medical Institute Buenos Aires
Argentina Allende Sanatorium Córdoba
Argentina Cordoba Private Hospital Córdoba
Argentina Mayo Private Sanatorium Córdoba
Argentina Italian Hospital of Mendoza Mendoza
Australia Monash Health Clayton Victoria
Australia Alfred Health Melbourne Victoria
Australia Peter MacCallum Cancer Centre Melbourne Victoria
Australia Westmead Public Hospital Northmead New South Wales
Australia Royal Melbourne Hospital (RMH) Parkville Victoria
Belgium Brugmann University Hospital Center Brussels
Belgium Erasme Hospital Brussels
Belgium Saint Luc University Hospital Brussels
Belgium University Hospital Brussels Brussels
Belgium University Hospitals Leuven, Campus Gasthuisberg Leuven
Bulgaria Multiprofile Hospital for Active Treatment Puls Blagoevgrad
Bulgaria University Multiprofile Hospital for Active Treatment and Emergency Medicine N.I. Pirogov EAD Sofia
Bulgaria University Multiprofile Hospital for Active Treatment and Emergency Medicine N.I. Pirogov EAD, Sofia, Clinic of Purulent-Septic Surgery Sofia
China The First Affiliated Hospital of Bengbu Medical College Bengbu Anhui
China The Second Xiangya Hospital of Central South University Changsha Hunan
China West China Hospital, Sichuan University Chengdu Sichuan
China Chongqing People's Hospital Chongqing Chongqing
China Guangdong Provincial People's Hospital Guangzhou Guangdong
China Guangzhou First People's Hospital Guangzhou Guangdong
China The First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong
China The Second Hospital of Anhui Medical University Hefei Anhui
China The Second People's Hospital of Hefei Hefei Anhui
China Nanjing First Hospital Nanjing Jiangsu
China Qingyuan People's Hospital Qingyuan Guangdong
China Huashan Hospital Affiliated Fudan University Shanghai
China Shanghai Pulmonary Hospital Shanghai
China General Hospital of Tianjin Medical University Tianjin
China Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences Tianjin
China Zhongnan Hospital of Wuhan University Wuhan Hubei
China Zibo Central Hospital Zibo Shandong
Colombia CEQUIN Foundation Cardiomet Armenia
Colombia De La Costa Clinic Ltd. Barranquilla
Colombia University IPS - Leon XIII Clinic Medellín
France Amiens Picardie University Hospital - South Amiens
France Centre Hospitalier Victor Dupouy - Argenteuil Argenteuil
France Roger Salengro Hospital Lille
France Marseille University Hospital Center - North Hospital Marseille
France Hotel Dieu Hospital Nantes University Hospital Center Nantes
France Paris University Hospitals Center - Cochin Hospital Paris
France Saint-Louis Hospital Paris
France University Hospital Center of Poitiers Poitiers
France Civil Hospital of Strasbourg Strasbourg
France Tours University Hospital Center, Bretonneau Hospital Tours
Germany University Hospital Köln Cologne
Germany University Hospital Freiburg Freiburg
Germany Johannes Gutenberg University Medical Center Mainz
Greece General Hospital of Athens "Evangelismos" Athens
Greece General Hospital of Athens "Evangelismos", 5th Department of Internal Medicine and Infectious Diseases Unit Athens
Greece General Hospital of Athens "Laikon" Athens
Greece General Hospital of Athens "Laikon", Infectious Diseases Unit Athens
Greece General Hospital of Thessaloniki Ippokratio Thessaloníki
Israel Edith Wolfson Medical Center H_olon
Israel Bnai Zion Medical Center Haifa
Israel Lady Davis Carmel Medical Center Haifa
Israel Rambam Health Care Campus Haifa
Israel Hadassah Medical Center Jerusalem
Israel The Baruch Padeh Medical Center Nazareth
Israel Ziv Medical Center Safed
Israel The Tel Aviv Sourasky Medical Center Tel Aviv
Israel Chaim Sheba Medical Center Tel Hashomer
Italy Polyclinic S. Orsola-Malpighi, Dept. of Organ Impairment and Transplants Bologna
Italy ASST Large Metropolitan Hospital Niguarda, Infectious Diseases Department Milan
Italy University Hospital of Modena Modena
Italy University Polyclinic Hospital of Modena Modena
Italy University of Milano-Bicocca - San Gerardo Hospital Monza
Italy University Polyclinic Hospital "Paolo Giaccone" Palermo, Infectious Disease Department, ICU Palermo
Italy University Polyclinic Foundation Agostino Gemelli - IRCCS Rome
Italy Integrated University Health Authority of Trieste Trieste
Italy Integrated University Hospital "Santa Maria della Misericordia" of Udine Udine
Korea, Republic of Dong-A University Hospital Busan
Korea, Republic of Chung-Ang University Hospital Seoul
Korea, Republic of Samsung Medical Center Seoul
Korea, Republic of Severance Hospital, Yonsei University Health System Seoul
Korea, Republic of Ajou University Hospital Suwon
Korea, Republic of Wonju Severance Christian Hospital Wonju Gangwon-do
Singapore National University Hospital Singapore
Singapore Tan Tock Seng Hospital Singapore
Spain University Hospital Germans Trias i Pujol Badalona
Spain University Hospital Cruces Baracaldo
Spain Hospital Clinic of Barcelona Barcelona
Spain Hospital del Mar, Department of Infectious Diseases Barcelona
Spain Parc Tauli Health Corporation Barcelona
Spain University Hospital Vall d'Hebron (HUVH) Barcelona
Spain General University Hospital Gregorio Maranon Madrid
Spain La Paz University Hospital Madrid
Spain University Hospital Clinical San Carlos Madrid
Spain University Hospital Ramon y Cajal Madrid
Spain University Hospital Puerta de Hierro Majadahonda Majadahonda
Spain University Hospital Virgen Macarena Sevilla
Spain University and Polytechnic Hospital La Fe Valencia
Taiwan Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung
Taiwan China Medical University Hospital Taichung
Taiwan National Taiwan University Hospital Taipei
Taiwan Taipei Veterans General Hospital Taipei
Taiwan Linkou Chang Gung Memorial Hospital Taoyuan City
Thailand King Chulalongkorn Memorial Hospital Bangkok
Thailand Rajavithi Hospital Bangkok
Thailand Ramathibodi Hospital Bangkok
Thailand Siriraj Hospital Bangkok
Thailand Maharaj Nakorn Chiang Mai Hospital Chiang Mai
Thailand Srinagarind Hospital Khon Kaen
Thailand Thammasat University Hospital Pathum Thani
Thailand Songklanagarind Hospital Songkhla
Turkey Ankara University School of Medicine Ankara
Turkey Hacettepe University School of Medicine Ankara
Turkey Istanbul University School of Medicine Istanbul
Turkey Marmara University Pendik Training and Research Hospital Istanbul
Turkey Medipol Mega University Hospital Istanbul
United States Emory University Hospital Atlanta Georgia
United States Augusta University Augusta Georgia
United States Johns Hopkins Baltimore Maryland
United States University of Alabama Birmingham Alabama
United States Mecury Street Medical Butte Montana
United States University of North Carolina Chapel Hill North Carolina
United States Henry Ford Health System Detroit Michigan
United States Duke University Medical Center Durham North Carolina
United States University of Mississippi Medical Center Jackson Mississippi
United States University of Minnesota Minneapolis Minnesota
United States University of Pittsburgh Falk Medical Center Pittsburgh Pennsylvania
United States Carilion Clinic Roanoke Virginia
United States Mayo Clinic Hospital-Rochester Rochester Minnesota
United States UC Davis Sacramento California
United States Washington University St. Louis Saint Louis Missouri
United States The University of Texas Health Science Center at San Antonio San Antonio Texas
United States Baylor Scott and White Medical Center Temple Texas
United States ID Clinical Research, Ltd. Toledo Ohio
United States Reading Hospital and Medical Center West Reading Pennsylvania

Sponsors (1)

Lead Sponsor Collaborator
Cidara Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Bulgaria,  China,  Colombia,  France,  Germany,  Greece,  Israel,  Italy,  Korea, Republic of,  Singapore,  Spain,  Taiwan,  Thailand,  Turkey, 

Outcome

Type Measure Description Time frame Safety issue
Primary All-Cause Mortality (US FDA Only) The number and percentage of subjects in each treatment group who are alive and deceased (or with missing data) in the mITT population. Day 30 (-2 days)
Primary Global Response as Assessed by Data Review Committee (EU European Medicines Agency [EMA] Only) The number and percentage of subjects in each treatment group who have a global response of cure (clinical cure as assessed by the Investigator, radiological cure [for qualifying invasive candidiasis subjects at baseline], and mycological eradication, as confirmed by the Data Review Committee [DRC]), failure and indeterminate in the mITT population. A global response of cure is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the global responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 7 (Global Response) of the clinical protocol. Day 14 (±1 day)
Secondary Global Response as Assessed by Data Review Committee (US FDA Only) The number and percentage of subjects in each treatment group who have a global response of cure (clinical cure as assessed by the Investigator, radiological cure [for qualifying invasive candidiasis subjects at baseline], and mycological eradication, as confirmed by the Data Review Committee [DRC]), failure and indeterminate in the mITT population. A global response of cure is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the global responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 7 (Global Response) of the clinical protocol. Day 14 (±1 day)
Secondary All-Cause Mortality (EU EMA Only) The number and percentage of subjects in each treatment group who are alive and deceased (or with missing data) in the mITT population. Day 30 (-2 days)
Secondary Comparison of Global Response (as Assessed by the DRC) by Visit The number and percentage of subjects in each treatment group who have a global response of cure (clinical cure as assessed by the Investigator, radiological cure [for qualifying invasive candidiasis subjects at baseline], and mycological eradication, as confirmed by the Data Review Committee [DRC]), failure and indeterminate in the mITT population. A global response of cure is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the global responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 7 (Global Response) of the clinical protocol. Day 5, Day 30 (-2 days), End of Treatment (EOT) (=2 days of last dose) and Follow-up (Days 52-59)
Secondary Comparison of Mycological Eradication by Visit The number and percentage of subjects in each treatment group who have a mycological response of eradication, failure, or indeterminate in the mITT population. A mycological response of eradication means clearance of objective evidence of infection and is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was eradication or failure. Definitions for the mycological responses of eradication, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 8 (Mycological Response) of the clinical protocol.
Note: Eradication includes both documented and presumed eradication.
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)
Secondary Comparison of Investigators' Assessment of Clinical Response by Visit The number and percentage of subjects in each treatment group for whom the Investigator determined a clinical response of cure, failure, or indeterminate in the mITT population. A clinical response of cure, as assessed by the Investigator, is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the clinical responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 9 (Investigator's Assessment of Clinical Response) of the clinical protocol. 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)
Secondary Comparison of Radiological Response by Investigator by Visit The number and percentage of subjects with invasive candidiasis (documented by radiologic/imaging evidence at baseline) in each treatment group who have a radiological response (as assessed by the Investigator) of cure, failure, and indeterminate in the mITT population. A radiological response of cure is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the radiological responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 10 (Radiological Response) of the clinical protocol. 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)
Secondary Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] The number and percentage of subjects in each treatment group that experienced at least one treatment-emergent adverse event (TEAE) based on clinical chemistry, hematology and urine analysis laboratory test, vital sign, physical exams and electrocardiogram (ECG) abnormalities.
Notes: A subject with multiple adverse events (AEs) was counted only once. TEAE was defined as an AE that occurred during or after study drug administration and up through the Follow-up visit. The maximum severity and strongest relationship were counted for subjects with multiple events.
Day 1 through Follow-up Visit (Days 52-59)
Secondary Evaluate Pharmacokinetics (Cmax) Evaluate the maximum plasma concentration (Cmax) of rezafungin for injection. Day 1, 10 minutes before the end of infusion
Secondary Evaluate Pharmacokinetics (Cmin) Evaluate the minimum plasma concentration (Cmin) of rezafungin for injection. Day 8, pre-dose, within 30 minutes prior to the start of infusion
Secondary Evaluate Pharmacokinetics (Cmin) Evaluate the minimum plasma concentration (Cmin) of rezafungin for injection. Day 15, pre-dose, within 30 minutes prior to the start of infusion
Secondary Evaluate Pharmacokinetics (Cmin) Evaluate the minimum plasma concentration (Cmin) of rezafungin for injection. Day 22, pre-dose, within 30 minutes prior to the start of infusion
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