CD101 Compared to Caspofungin Followed by Oral Step Down in Subjects With Candidemia and/or Invasive Candidiasis-Bridging Extension

NCT ID: NCT02734862

Last Updated: 2020-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 207 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-26
• Study Completion Date: 2019-07-31

Brief Summary

The purpose of this study is to determine if intravenous CD101 is safe and effective in the treatment of candidemia and/or invasive candidiasis when compared to caspofungin (followed by oral fluconazole).

Detailed Description

This Bridging Extension is to determine if intravenous CD101 is safe [Day 45- 52 for subjects with candidemia only, or Day 52- 59 for subjects with invasive candidiasis with or without candidemia] and effective [Day 14 (± 1 day)] in the treatment of candidemia and/or invasive candidiasis when compared to caspofungin (followed by oral fluconazole).

Conditions

Candidemia; Mycoses; Fungal Infection; Fungemia; Invasive Candidiasis

Keywords

mycoses

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

Group Type: EXPERIMENTAL

CD101

Intervention Type: DRUG

Intravenous antifungal therapy

intravenous placebo

Intervention Type: DRUG

normal saline

oral placebo

Intervention Type: DRUG

microcrystalline cellulose

Group 3

Subjects in the caspofungin group will receive IV caspofungin (a single 70 mg loading dose on Day 1 followed by 50 mg once daily) for ≥3 days up to a maximum of 21 days for subjects with candidemia only and up to a maximum of 28 days for subjects with IC (with or without candidemia).

After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral step-down therapy of fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 400 mg [2 capsules]/day thereafter). 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

Group 2

Subjects in the CD101 IV treatment group 2 (Part B Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose of 200 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

Group Type: EXPERIMENTAL

CD101

Intervention Type: DRUG

Intravenous antifungal therapy

intravenous placebo

Intervention Type: DRUG

normal saline

oral placebo

Intervention Type: DRUG

microcrystalline cellulose

Interventions

CD101

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

CD101 for Injection; Cancidas; generic fluconazole; placebo infusion; encapsulated cellulose

Eligibility Criteria

Inclusion Criteria

• mycological diagnosis of candidemia and/or invasive candidiasis from a sample taken less than or equal to 96 hours before randomization (defined as: at least 1 blood culture positive for Candida or positive test for Candida from a sponsor approved rapid diagnostic test or positive gram stain for yeast or positive culture for Candida spp. from a specimen obtained from a normally sterile site)
• willing to initiate or continue medical treatment to cure infections, including receipt of antibiotics and surgical procedures, if required. Patients receiving only medications and measures for comfort and not cure should not be enrolled.
• female subjects of child bearing potential <2 years post menopausal must agree to one barrier method and one highly effective method of birth control or sexual abstinence.
• male subjects must be vasectomized, abstain from sexual intercourse, or agree to use barrier contraception (condom with spermicide), and also agree not to donate sperm from first dose of CD101 (Day 1) until 90 days following last administration of study drug.
• 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 their behalf.
• presence of one or more systemic signs attributable to candidemia and/or invasive candidiasis

Exclusion Criteria

• Any of the following forms of IC:

1. Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed)

2. Osteomyelitis

3. Endocarditis or myocarditis

4. Meningitis, endophthalmitis, or any central nervous system infection

• neutropenia
• alanine aminotransferase or aspartate aminotransferase levels >10 fold the upper limit of normal
• severe hepatic impairment in subjects with a history of chronic cirrhosis
• greater than 48 hours systemic antifungal treatment at approved doses to treat candidemia
• pregnant females
• lactating females who are nursing
• known hypersensitivity to CD101, caspofungin, any echinocandin, or to any of their excipients
• previous participation in this or any previous CD101 study
• recent use of an investigational medicinal product within 28 days of first dose of study drug or presence of an investigational device at the time of screening
• Principal Investigator considers the subject should not participate
• presence of indwelling vascular catheter or device that cannot be removed and is likely to be the source of candidemia

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cidara Therapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Taylor Sandison, MD MPH

Role: STUDY_DIRECTOR

Cidara Therapeutics

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of California - Davis

Davis, California, United States

University of Miami Miller School of Medicine

Miami, Florida, United States

Augusta University

Augusta, Georgia, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Harper University Hospital

Detroit, Michigan, United States

Henry Ford Health System

Detroit, Michigan, United States

William Beaumont Hospital

Royal Oak, Michigan, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mercury Street Medical

Butte, Montana, United States

Albany Medical Center

Albany, New York, United States

Mercy Health - St. Vincent Medical Center - ID Clinical Research

Toledo, Ohio, United States

Reading Hospital and Medical Center

West Reading, Pennsylvania, United States

University of Texas Health Science Center at Houston

Houston, Texas, United States

Virginia Tech, Carillion School of Medicine

Roanoke, Virginia, United States

Jules Bordet Institute

Brussels, , Belgium

CHU Brugman

Brussels, , Belgium

Erasme Hospital

Brussels, , Belgium

UCL Saint-LUC

Brussels, , Belgium

UZ Gent Algemene Inwendige Zietken

Ghent, , Belgium

University Hospital Brussels

Jette, , Belgium

University Hospital Leuven

Leuven, , Belgium

CHU Sart-Tillman

Liège, , Belgium

University Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski", Sofia, Clinic of Clinical Hematology

Sofia, , Bulgaria

University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Burns and Plastic Surgery Clinic, Department of Anesthesiology and Intensive Care

Sofia, , Bulgaria

Juravinski Hospital and Cancer Centre/Hamilton Health Sciences

Hamilton, Ontario, Canada

Toronto General Hospital-University Health Network

Toronto, Ontario, Canada

CIUSSS de L'Est-de-l'Île-De-Montréal, Installation Hôpital

Montreal, Quebec, Canada

McGill University Health Centre-Research Institute

Montreal, Quebec, Canada

University General Hospital "Attikon", 2nd Department of Critical Care

Athens, Chaidari, Greece

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

Athens, , Greece

Laiko General Hospital of Athens

Athens, , Greece

Henry Dunant Hospital Center

Athens, , Greece

General Hospital of Athens "Evangelismos", Department of Critical Care

Athens, , Greece

University Hospital of Larissa, Department of Critical Care Unit

Thessaloniki, , Greece

Medical Centre, Hungarian Defence Forces, Central Intensive Care Unit and Anesthesiology Department

Budapest, , Hungary

Fejer County St. Gyorgy University Teaching Hospital, Central Department of Anesthesiology and Intensive Care Unit

Szeged, , Hungary

Polyclinic S. Orsola-Malpighi, Department of Organ Impairment and Transplants, Operative Unit of Infectious Diseases

Bologna, , Italy

University Polyclinic Hospital of Modena, Department of General and Specialist Surgery, Operative Unit of Anesthesia and Intensive Care I

Modena, , Italy

University Hospital of Pisa, Department of Gastroenterology and Infectious Diseases, Operative Unit of Infectious Diseases

Pisa, , Italy

University Polyclinic Agostino Gemelli, Complex Operative Unit of Infectious Diseases 2

Rome, , Italy

Hospital Maggiore University Hospital Ospedali Riuniti of Trieste Dept of ID

Trieste, , Italy

University Hospital "Santa Maria della Misericordia" of Udine, Department of Specialist Medicine, Clinic of Infectious Diseases

Udine, , Italy

Craiova County Emergency Clinical Hospital, ATI Clinic

Craiova, Dolj, Romania

Institute of Infectious Diseases

Bucharest, Sector 2, Romania

Pius Brinzeu County Emergency Clinical Hospital, Anesthesia and Intensive Care Department (Romania)

Timișoara, Timiș County, Romania

Sfanta Parascheva Parascheva Iasi Clinical Hospital for Infectious Diseases

Iași, , Romania

Kuban State Medical University

Krasnodar, , Russia

Territorial Clinical Hospital

Krasnoyarsk, , Russia

Mariinskaya City Hospital

Saint Petersburg, , Russia

University Hospital Vall d'Hebron (HUVH), Department of Infectious Diseases

Barcelona, Catalonia, Spain

Hospital Clinic i Provincial de Barcelona, Department of Infectious Diseases

Barcelona, Catalonia, Spain

University Hospital Cruces, Unit of Infectious Diseases

Barakaldo, , Spain

Hospital del Mar, Department of Infectious Diseases

Barcelona, , Spain

General University Hospital Gregorio Maranon

Madrid, , Spain

University Hospital Ramon y Cajal

Madrid, , Spain

University Hospital Clinical San Carlos

Madrid, , Spain

University Hospital La Paz

Madrid, , Spain

University Hospital Virgen Macarena

Seville, , Spain

University Hospital Nuestra Senora de Valme,

Seville, , Spain

University Hospital Virgen del Rocio (HUVR)

Seville, , Spain

University Hospital La Fe

Valencia, , Spain

Countries

United States; Belgium; Bulgaria; Canada; Greece; Hungary; Italy; Romania; Russia; Spain

References

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)

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, Soriano A, Skoutelis A, Vazquez JA, Honore PM, Horcajada JP, Spapen H, Bassetti M, Ostrosky-Zeichner L, Das AF, Viani RM, Sandison T, Pappas PG. Rezafungin Versus Caspofungin in a Phase 2, Randomized, Double-blind Study for the Treatment of Candidemia and Invasive Candidiasis: The STRIVE Trial. Clin Infect Dis. 2021 Dec 6;73(11):e3647-e3655. doi: 10.1093/cid/ciaa1380.

Reference Type: DERIVED

PMID: 32955088 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-005599-51

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CD101.IV.2.03

Identifier Type: -

Identifier Source: org_study_id