Study of Rezafungin Compared to Caspofungin in Subjects With Candidemia and/or Invasive Candidiasis

NCT ID: NCT03667690

Last Updated: 2023-01-06

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

199 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-10-07

Study Completion Date

2021-10-07

Brief Summary

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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

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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.

Conditions

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Candidemia Mycoses Fungal Infection Invasive Candidiases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Rezafungin for Injection

Intervention Type DRUG

Intravenous antifungal therapy

oral placebo

Intervention Type DRUG

Microcrystalline cellulose

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.

Group Type ACTIVE_COMPARATOR

Caspofungin

Intervention Type DRUG

Intravenous antifungal therapy

Fluconazole

Intervention Type DRUG

Oral antifungal therapy

intravenous placebo

Intervention Type DRUG

Normal saline

Interventions

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Rezafungin for Injection

Intravenous antifungal therapy

Intervention Type DRUG

Caspofungin

Intravenous antifungal therapy

Intervention Type DRUG

Fluconazole

Oral antifungal therapy

Intervention Type DRUG

intravenous placebo

Normal saline

Intervention Type DRUG

oral placebo

Microcrystalline cellulose

Intervention Type DRUG

Other Intervention Names

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Cancidas generic fluconazole placebo infusion encapsulated cellulose

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cidara Therapeutics Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Taylor Sandison, MD, MPH

Role: STUDY_DIRECTOR

Cidara Therapeutics Inc.

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

UC Davis

Sacramento, California, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

Augusta University

Augusta, Georgia, United States

Site Status

Johns Hopkins

Baltimore, Maryland, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Hospital-Rochester

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Washington University St. Louis

St Louis, Missouri, United States

Site Status

Mecury Street Medical

Butte, Montana, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

ID Clinical Research, Ltd.

Toledo, Ohio, United States

Site Status

University of Pittsburgh Falk Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Reading Hospital and Medical Center

West Reading, Pennsylvania, United States

Site Status

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Baylor Scott and White Medical Center

Temple, Texas, United States

Site Status

Carilion Clinic

Roanoke, Virginia, United States

Site Status

Alexander Fleming Specialized Medical Institute

Buenos Aires, , Argentina

Site Status

Cordoba Private Hospital

Córdoba, , Argentina

Site Status

Allende Sanatorium

Córdoba, , Argentina

Site Status

Mayo Private Sanatorium

Córdoba, , Argentina

Site Status

Italian Hospital of Mendoza

Mendoza, , Argentina

Site Status

Westmead Public Hospital

Northmead, New South Wales, Australia

Site Status

Monash Health

Clayton, Victoria, Australia

Site Status

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status

Alfred Health

Melbourne, Victoria, Australia

Site Status

Royal Melbourne Hospital (RMH)

Parkville, Victoria, Australia

Site Status

Brugmann University Hospital Center

Brussels, , Belgium

Site Status

Erasme Hospital

Brussels, , Belgium

Site Status

University Hospital Brussels

Brussels, , Belgium

Site Status

Saint Luc University Hospital

Brussels, , Belgium

Site Status

University Hospitals Leuven, Campus Gasthuisberg

Leuven, , Belgium

Site Status

Multiprofile Hospital for Active Treatment Puls

Blagoevgrad, , Bulgaria

Site Status

University Multiprofile Hospital for Active Treatment and Emergency Medicine N.I. Pirogov EAD, Sofia, Clinic of Purulent-Septic Surgery

Sofia, , Bulgaria

Site Status

University Multiprofile Hospital for Active Treatment and Emergency Medicine N.I. Pirogov EAD

Sofia, , Bulgaria

Site Status

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, China

Site Status

The Second People's Hospital of Hefei

Hefei, Anhui, China

Site Status

The Second Hospital of Anhui Medical University

Hefei, Anhui, China

Site Status

Chongqing People's Hospital

Chongqing, Chongqing Municipality, China

Site Status

Guangzhou First People's Hospital

Guangzhou, Guangdong, China

Site Status

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China

Site Status

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status

Qingyuan People's Hospital

Qingyuan, Guangdong, China

Site Status

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, China

Site Status

The Second Xiangya Hospital of Central South University

Changsha, Hunan, China

Site Status

Nanjing First Hospital

Nanjing, Jiangsu, China

Site Status

Zibo Central Hospital

Zibo, Shandong, China

Site Status

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Site Status

Huashan Hospital Affiliated Fudan University

Shanghai, , China

Site Status

Shanghai Pulmonary Hospital

Shanghai, , China

Site Status

Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, , China

Site Status

General Hospital of Tianjin Medical University

Tianjin, , China

Site Status

CEQUIN Foundation Cardiomet

Armenia, , Colombia

Site Status

De La Costa Clinic Ltd.

Barranquilla, , Colombia

Site Status

University IPS - Leon XIII Clinic

Medellín, , Colombia

Site Status

Amiens Picardie University Hospital - South

Amiens, , France

Site Status

Centre Hospitalier Victor Dupouy - Argenteuil

Argenteuil, , France

Site Status

Roger Salengro Hospital

Lille, , France

Site Status

Marseille University Hospital Center - North Hospital

Marseille, , France

Site Status

Hotel Dieu Hospital Nantes University Hospital Center

Nantes, , France

Site Status

Saint-Louis Hospital

Paris, , France

Site Status

Paris University Hospitals Center - Cochin Hospital

Paris, , France

Site Status

University Hospital Center of Poitiers

Poitiers, , France

Site Status

Civil Hospital of Strasbourg

Strasbourg, , France

Site Status

Tours University Hospital Center, Bretonneau Hospital

Tours, , France

Site Status

University Hospital Köln

Cologne, , Germany

Site Status

University Hospital Freiburg

Freiburg im Breisgau, , Germany

Site Status

Johannes Gutenberg University Medical Center

Mainz, , Germany

Site Status

General Hospital of Athens "Evangelismos", 5th Department of Internal Medicine and Infectious Diseases Unit

Athens, , Greece

Site Status

General Hospital of Athens "Evangelismos"

Athens, , Greece

Site Status

General Hospital of Athens "Laikon", Infectious Diseases Unit

Athens, , Greece

Site Status

General Hospital of Athens "Laikon"

Athens, , Greece

Site Status

General Hospital of Thessaloniki Ippokratio

Thessaloniki, , Greece

Site Status

Bnai Zion Medical Center

Haifa, , Israel

Site Status

Lady Davis Carmel Medical Center

Haifa, , Israel

Site Status

Rambam Health Care Campus

Haifa, , Israel

Site Status

Edith Wolfson Medical Center

Holon, , Israel

Site Status

Hadassah Medical Center

Jerusalem, , Israel

Site Status

The Baruch Padeh Medical Center

Nazareth, , Israel

Site Status

Ziv Medical Center

Safed, , Israel

Site Status

The Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Chaim Sheba Medical Center

Tel Litwinsky, , Israel

Site Status

Polyclinic S. Orsola-Malpighi, Dept. of Organ Impairment and Transplants

Bologna, , Italy

Site Status

ASST Large Metropolitan Hospital Niguarda, Infectious Diseases Department

Milan, , Italy

Site Status

University Polyclinic Hospital of Modena

Modena, , Italy

Site Status

University Hospital of Modena

Modena, , Italy

Site Status

University of Milano-Bicocca - San Gerardo Hospital

Monza, , Italy

Site Status

University Polyclinic Hospital "Paolo Giaccone" Palermo, Infectious Disease Department, ICU

Palermo, , Italy

Site Status

University Polyclinic Foundation Agostino Gemelli - IRCCS

Rome, , Italy

Site Status

Integrated University Health Authority of Trieste

Trieste, , Italy

Site Status

Integrated University Hospital "Santa Maria della Misericordia" of Udine

Udine, , Italy

Site Status

National University Hospital

Singapore, , Singapore

Site Status

Tan Tock Seng Hospital

Singapore, , Singapore

Site Status

Wonju Severance Christian Hospital

Wŏnju, Gangwon-do, South Korea

Site Status

Dong-A University Hospital

Busan, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

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Chung-Ang University Hospital

Seoul, , South Korea

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Ajou University Hospital

Suwon, , South Korea

Site Status

University Hospital Germans Trias i Pujol

Badalona, , Spain

Site Status

University Hospital Cruces

Barakaldo, , Spain

Site Status

Hospital del Mar, Department of Infectious Diseases

Barcelona, , Spain

Site Status

University Hospital Vall d'Hebron (HUVH)

Barcelona, , Spain

Site Status

Hospital Clinic of Barcelona

Barcelona, , Spain

Site Status

Parc Tauli Health Corporation

Barcelona, , Spain

Site Status

General University Hospital Gregorio Maranon

Madrid, , Spain

Site Status

University Hospital Ramon y Cajal

Madrid, , Spain

Site Status

University Hospital Clinical San Carlos

Madrid, , Spain

Site Status

La Paz University Hospital

Madrid, , Spain

Site Status

University Hospital Puerta de Hierro Majadahonda

Majadahonda, , Spain

Site Status

University Hospital Virgen Macarena

Seville, , Spain

Site Status

University and Polytechnic Hospital La Fe

Valencia, , Spain

Site Status

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

China Medical University Hospital

Taichung, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Linkou Chang Gung Memorial Hospital

Taoyuan, , Taiwan

Site Status

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Site Status

Rajavithi Hospital

Bangkok, , Thailand

Site Status

Ramathibodi Hospital

Bangkok, , Thailand

Site Status

Siriraj Hospital

Bangkok, , Thailand

Site Status

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, , Thailand

Site Status

Srinagarind Hospital

Khon Kaen, , Thailand

Site Status

Thammasat University Hospital

Pathum Thani, , Thailand

Site Status

Songklanagarind Hospital

Songkhla, , Thailand

Site Status

Hacettepe University School of Medicine

Ankara, , Turkey (Türkiye)

Site Status

Ankara University School of Medicine

Ankara, , Turkey (Türkiye)

Site Status

Istanbul University School of Medicine

Istanbul, , Turkey (Türkiye)

Site Status

Marmara University Pendik Training and Research Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Medipol Mega University Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Countries

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United States Argentina Australia Belgium Bulgaria China Colombia France Germany Greece Israel Italy Singapore South Korea Spain Taiwan Thailand Turkey (Türkiye)

References

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Honore PM, Bassetti M, Cornely OA, Dupont H, Fortun J, Kollef MH, Pappas P, Pullman J, Vazquez J, Bielicka I, Dickerson S, Manamley N, Sandison T, Thompson GR. Length of hospital and intensive care unit stay in patients with invasive candidiasis and/or candidemia treated with rezafungin: a pooled analysis of two randomised controlled trials. Crit Care. 2024 Nov 11;28(1):361. doi: 10.1186/s13054-024-05152-2.

Reference Type DERIVED
PMID: 39529079 (View on PubMed)

Honore PM, Girardis M, Kollef M, Cornely OA, Thompson GR 3rd, Bassetti M, Soriano A, Huang H, Vazquez J, Kullberg BJ, Pappas PG, Manamley N, Sandison T, Pullman J, Nseir S. Rezafungin versus caspofungin for patients with candidaemia or invasive candidiasis in the intensive care unit: pooled analyses of the ReSTORE and STRIVE randomised trials. Crit Care. 2024 Oct 28;28(1):348. doi: 10.1186/s13054-024-05117-5.

Reference Type DERIVED
PMID: 39468640 (View on PubMed)

Clarke F, Grenfell A, Chao S, Richards H, Korman T, Rogers B. Use of echinocandin outpatient parenteral antimicrobial therapy for the treatment of infection caused by Candida spp.: utilization, outcomes and impact of a change to weekly dosing. J Antimicrob Chemother. 2024 Nov 4;79(11):2896-2900. doi: 10.1093/jac/dkae302.

Reference Type DERIVED
PMID: 39259571 (View on PubMed)

Soriano A, Honore PM, Cornely OA, Chayakulkeeree M, Bassetti M, Haihui H, Dupont H, Kim YK, Kollef M, Kullberg BJ, Manamley N, Pappas P, Pullman J, Sandison T, Dignani C, Vazquez JA, Thompson GR 3rd. Treatment Outcomes Among Patients With a Positive Candida Culture Close to Randomization Receiving Rezafungin or Caspofungin in the ReSTORE Study. Clin Infect Dis. 2024 Sep 26;79(3):672-681. doi: 10.1093/cid/ciae363.

Reference Type DERIVED
PMID: 38985561 (View on PubMed)

Smith HL, Bensman TJ, Mishra S, Li X, Dixon CA, Sheikh J, McMaster OG, Joshi A, Rubin DB, Goodwin A, Miller TJ, Danielsen ZY, Syed I, Shukla SJ, Iarikov D, Kim PW, Farley JJ. Regulatory Considerations in the Approval of Rezafungin (Rezzayo) for the Treatment of Candidemia and Invasive Candidiasis in Adults. J Infect Dis. 2024 Aug 16;230(2):505-513. doi: 10.1093/infdis/jiae146.

Reference Type DERIVED
PMID: 38502709 (View on PubMed)

Thompson GR 3rd, Soriano A, Honore PM, Bassetti M, Cornely OA, Kollef M, Kullberg BJ, Pullman J, Hites M, Fortun J, Horcajada JP, Kotanidou A, Das AF, Sandison T, Aram JA, Vazquez JA, Pappas PG. Efficacy and safety of rezafungin and caspofungin in candidaemia and invasive candidiasis: pooled data from two prospective randomised controlled trials. Lancet Infect Dis. 2024 Mar;24(3):319-328. doi: 10.1016/S1473-3099(23)00551-0. Epub 2023 Nov 23.

Reference Type DERIVED
PMID: 38008099 (View on PubMed)

Thompson GR 3rd, Soriano A, Cornely OA, Kullberg BJ, Kollef M, Vazquez J, Honore PM, Bassetti M, Pullman J, Chayakulkeeree M, Poromanski I, Dignani C, Das AF, Sandison T, Pappas PG; ReSTORE trial investigators. Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial. Lancet. 2023 Jan 7;401(10370):49-59. doi: 10.1016/S0140-6736(22)02324-8. Epub 2022 Nov 25.

Reference Type DERIVED
PMID: 36442484 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33438477 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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CD101.IV.3.05

Identifier Type: -

Identifier Source: org_study_id

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