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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03667690




Registration number
NCT03667690
Ethics application status
Date submitted
30/08/2018
Date registered
12/09/2018
Date last updated
6/01/2023

Titles & IDs
Public title
Study of Rezafungin Compared to Caspofungin in Subjects With Candidemia and/or Invasive Candidiasis
Scientific 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
Secondary ID [1] 0 0
CD101.IV.3.05
Universal Trial Number (UTN)
Trial acronym
ReSTORE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Candidemia 0 0
Mycoses 0 0
Fungal Infection 0 0
Invasive Candidiases 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Rezafungin for Injection
Treatment: Drugs - Caspofungin
Treatment: Drugs - Fluconazole
Treatment: Drugs - intravenous placebo
Treatment: Drugs - oral placebo

Experimental: Group 1: Rezafungin for Injection - Subjects in Rezafungin treatment group will receive a 400 mg loading dose in Week 1, followed by 200 mg once weekly, for a total of 2 to 4 doses.

Daily intravenous placebo infusions, when not administered Rezafungin and a daily placebo for oral step-down therapy (first eligibility on Day 4 or later as advised by a site's national/regional/local guidelines) administered every day.

Active comparator: Group 2: Caspofungin - Subjects in caspofungin arm will receive a total treatment of =14 days beginning with a single caspofungin 70 mg IV loading dose on Day 1 followed by 50 mg IV once daily up to 28 days. After =3 days of caspofungin treatment(or the minimum duration of IV therapy advised by the site's national/regional/local guidelines, whichever is greater), subjects may be switched to oral fluconazole if specific parameters are met.

If the subject qualifies, then oral step-down therapy of fluconazole (6 mg/kg to the nearest 200 mg) is administered. After switch to oral step down before Day 8, subjects in the caspofungin group will receive IV placebo on Day 8 to preserve the study blind.


Treatment: Drugs: Rezafungin for Injection
Intravenous antifungal therapy

Treatment: Drugs: Caspofungin
Intravenous antifungal therapy

Treatment: Drugs: Fluconazole
Oral antifungal therapy

Treatment: Drugs: intravenous placebo
Normal saline

Treatment: Drugs: oral placebo
Microcrystalline cellulose

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
All-Cause Mortality (US FDA Only)
Timepoint [1] 0 0
Day 30 (-2 days)
Primary outcome [2] 0 0
Global Response as Assessed by Data Review Committee (EU European Medicines Agency [EMA] Only)
Timepoint [2] 0 0
Day 14 (±1 day)
Secondary outcome [1] 0 0
Global Response as Assessed by Data Review Committee (US FDA Only)
Timepoint [1] 0 0
Day 14 (±1 day)
Secondary outcome [2] 0 0
All-Cause Mortality (EU EMA Only)
Timepoint [2] 0 0
Day 30 (-2 days)
Secondary outcome [3] 0 0
Comparison of Global Response (as Assessed by the DRC) by Visit
Timepoint [3] 0 0
Day 5, Day 30 (-2 days), End of Treatment (EOT) (=2 days of last dose) and Follow-up (Days 52-59)
Secondary outcome [4] 0 0
Comparison of Mycological Eradication by Visit
Timepoint [4] 0 0
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 outcome [5] 0 0
Comparison of Investigators' Assessment of Clinical Response by Visit
Timepoint [5] 0 0
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 outcome [6] 0 0
Comparison of Radiological Response by Investigator by Visit
Timepoint [6] 0 0
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 outcome [7] 0 0
Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability]
Timepoint [7] 0 0
Day 1 through Follow-up Visit (Days 52-59)
Secondary outcome [8] 0 0
Evaluate Pharmacokinetics (Cmax)
Timepoint [8] 0 0
Day 1, 10 minutes before the end of infusion
Secondary outcome [9] 0 0
Evaluate Pharmacokinetics (Cmin)
Timepoint [9] 0 0
Day 8, pre-dose, within 30 minutes prior to the start of infusion
Secondary outcome [10] 0 0
Evaluate Pharmacokinetics (Cmin)
Timepoint [10] 0 0
Day 15, pre-dose, within 30 minutes prior to the start of infusion
Secondary outcome [11] 0 0
Evaluate Pharmacokinetics (Cmin)
Timepoint [11] 0 0
Day 22, pre-dose, within 30 minutes prior to the start of infusion

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Westmead Public Hospital - Northmead
Recruitment hospital [2] 0 0
Monash Health - Clayton
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
Alfred Health - Melbourne
Recruitment hospital [5] 0 0
Royal Melbourne Hospital (RMH) - Parkville
Recruitment postcode(s) [1] 0 0
2152 - Northmead
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Mississippi
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
Montana
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
Argentina
State/province [15] 0 0
Buenos Aires
Country [16] 0 0
Argentina
State/province [16] 0 0
Córdoba
Country [17] 0 0
Argentina
State/province [17] 0 0
Mendoza
Country [18] 0 0
Belgium
State/province [18] 0 0
Brussels
Country [19] 0 0
Belgium
State/province [19] 0 0
Leuven
Country [20] 0 0
Bulgaria
State/province [20] 0 0
Blagoevgrad
Country [21] 0 0
Bulgaria
State/province [21] 0 0
Sofia
Country [22] 0 0
China
State/province [22] 0 0
Anhui
Country [23] 0 0
China
State/province [23] 0 0
Chongqing
Country [24] 0 0
China
State/province [24] 0 0
Guangdong
Country [25] 0 0
China
State/province [25] 0 0
Hubei
Country [26] 0 0
China
State/province [26] 0 0
Hunan
Country [27] 0 0
China
State/province [27] 0 0
Jiangsu
Country [28] 0 0
China
State/province [28] 0 0
Shandong
Country [29] 0 0
China
State/province [29] 0 0
Sichuan
Country [30] 0 0
China
State/province [30] 0 0
Shanghai
Country [31] 0 0
China
State/province [31] 0 0
Tianjin
Country [32] 0 0
Colombia
State/province [32] 0 0
Armenia
Country [33] 0 0
Colombia
State/province [33] 0 0
Barranquilla
Country [34] 0 0
Colombia
State/province [34] 0 0
Medellín
Country [35] 0 0
France
State/province [35] 0 0
Amiens
Country [36] 0 0
France
State/province [36] 0 0
Argenteuil
Country [37] 0 0
France
State/province [37] 0 0
Lille
Country [38] 0 0
France
State/province [38] 0 0
Marseille
Country [39] 0 0
France
State/province [39] 0 0
Nantes
Country [40] 0 0
France
State/province [40] 0 0
Paris
Country [41] 0 0
France
State/province [41] 0 0
Poitiers
Country [42] 0 0
France
State/province [42] 0 0
Strasbourg
Country [43] 0 0
France
State/province [43] 0 0
Tours
Country [44] 0 0
Germany
State/province [44] 0 0
Cologne
Country [45] 0 0
Germany
State/province [45] 0 0
Freiburg
Country [46] 0 0
Germany
State/province [46] 0 0
Mainz
Country [47] 0 0
Greece
State/province [47] 0 0
Athens
Country [48] 0 0
Greece
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Thessaloníki
Country [49] 0 0
Israel
State/province [49] 0 0
Haifa
Country [50] 0 0
Israel
State/province [50] 0 0
H_olon
Country [51] 0 0
Israel
State/province [51] 0 0
Jerusalem
Country [52] 0 0
Israel
State/province [52] 0 0
Nazareth
Country [53] 0 0
Israel
State/province [53] 0 0
Safed
Country [54] 0 0
Israel
State/province [54] 0 0
Tel Aviv
Country [55] 0 0
Israel
State/province [55] 0 0
Tel Hashomer
Country [56] 0 0
Italy
State/province [56] 0 0
Bologna
Country [57] 0 0
Italy
State/province [57] 0 0
Milan
Country [58] 0 0
Italy
State/province [58] 0 0
Modena
Country [59] 0 0
Italy
State/province [59] 0 0
Monza
Country [60] 0 0
Italy
State/province [60] 0 0
Palermo
Country [61] 0 0
Italy
State/province [61] 0 0
Rome
Country [62] 0 0
Italy
State/province [62] 0 0
Trieste
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Italy
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Udine
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Korea, Republic of
State/province [64] 0 0
Gangwon-do
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Korea, Republic of
State/province [65] 0 0
Busan
Country [66] 0 0
Korea, Republic of
State/province [66] 0 0
Seoul
Country [67] 0 0
Korea, Republic of
State/province [67] 0 0
Suwon
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Singapore
State/province [68] 0 0
Singapore
Country [69] 0 0
Spain
State/province [69] 0 0
Badalona
Country [70] 0 0
Spain
State/province [70] 0 0
Baracaldo
Country [71] 0 0
Spain
State/province [71] 0 0
Barcelona
Country [72] 0 0
Spain
State/province [72] 0 0
Madrid
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Spain
State/province [73] 0 0
Majadahonda
Country [74] 0 0
Spain
State/province [74] 0 0
Sevilla
Country [75] 0 0
Spain
State/province [75] 0 0
Valencia
Country [76] 0 0
Taiwan
State/province [76] 0 0
Kaohsiung
Country [77] 0 0
Taiwan
State/province [77] 0 0
Taichung
Country [78] 0 0
Taiwan
State/province [78] 0 0
Taipei
Country [79] 0 0
Taiwan
State/province [79] 0 0
Taoyuan City
Country [80] 0 0
Thailand
State/province [80] 0 0
Bangkok
Country [81] 0 0
Thailand
State/province [81] 0 0
Chiang Mai
Country [82] 0 0
Thailand
State/province [82] 0 0
Khon Kaen
Country [83] 0 0
Thailand
State/province [83] 0 0
Pathum Thani
Country [84] 0 0
Thailand
State/province [84] 0 0
Songkhla
Country [85] 0 0
Turkey
State/province [85] 0 0
Ankara
Country [86] 0 0
Turkey
State/province [86] 0 0
Istanbul

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Cidara Therapeutics Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Taylor Sandison, MD, MPH
Address 0 0
Cidara Therapeutics Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.