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

Phase 2

Completed

Conditions: Fungal Infection
Fungemia
Invasive Candidiasis
Candidemia
Mycoses

Interventions: Drug: CD101
Drug: Caspofungin
Drug: intravenous placebo
Drug: Fluconazole
Drug: oral placebo

Registration Number: NCT02734862

Lead Sponsor: Cidara Therapeutics Inc.

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 207

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	oral placebo	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 1	intravenous placebo	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 3	intravenous placebo	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 2	oral placebo	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 2	intravenous placebo	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 1	CD101	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 2	CD101	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 3	Caspofungin	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 3	Fluconazole	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.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment Emergent Adverse Events [Safety and Tolerability]	From first dose of study drug through Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia.	Number of Subjects with Incidence of Treatment Emergent Adverse Events based on clinical chemistry, hematology and urine analysis laboratory test, vital sign, physical exams and ECG abnormalities.
Resolution of Systemic Signs Attributable to Candidemia and/or Invasive Candidiasis and Mycological Eradication [Overall Success]	Day 14 (± 1 day)	Number of subjects with mycological eradication and complete resolution of all systemic signs of candidemia and/or invasive candidiasis which were present at baseline

Secondary Outcome Measures

Name	Time	Method
Clinical Cure	Day 14 (±1 day) and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia).	Evaluate clinical cure as assessed by the Investigator in the mITT population. Subjects must meet all of the following requirements: * Resolution of attributable systemic signs and symptoms of candidemia/IC that were present at baseline * No new systemic signs or symptoms attributable to candidemia/IC * No additional systemic antifungal therapy administered for candidemia/IC * The subject is alive
Evaluate PK (Cmax)	Day 1, 10 minutes before end of infusion (EOI)	Evaluate maximum plasma concentration (Cmax) (Part A only)
Mycological Eradication and Resolution of Systemic Signs	Day 5, and Follow-up (FU Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia.	Evaluate overall success signs (mycological eradication and resolution of systemic signs attributable to candidemia and/or IC) in the mITT population.
Evaluate PK (Cmin)	Day 15, predose	Evaluate minimum plasma concentration (Cmin) (Part A only)
Mycological Eradication	Day 5, Day 14 (±1 day), and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia)	Evaluate mycological success (eradication) in the mITT population.

Trial Locations

Locations (63): University Hospital La Paz
🇪🇸
Madrid, Spain
UCL Saint-LUC
🇧🇪
Brussels, Belgium
Virginia Tech, Carillion School of Medicine
🇺🇸
Roanoke, Virginia, United States
University of California - Davis
🇺🇸
Davis, California, United States
University Hospital Leuven
🇧🇪
Leuven, Belgium
University Hospital Cruces, Unit of Infectious Diseases
🇪🇸
Barakaldo, Spain
Henry Ford Health System
🇺🇸
Detroit, Michigan, United States
Reading Hospital and Medical Center
🇺🇸
West Reading, Pennsylvania, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Harper University Hospital
🇺🇸
Detroit, Michigan, United States
Juravinski Hospital and Cancer Centre/Hamilton Health Sciences
🇨🇦
Hamilton, Ontario, Canada
University Hospital Vall d'Hebron (HUVH), Department of Infectious Diseases
🇪🇸
Barcelona, Catalonia, Spain
UZ Gent Algemene Inwendige Zietken
🇧🇪
Gent, Belgium
University Hospital Ramon y Cajal
🇪🇸
Madrid, Spain
General University Hospital Gregorio Maranon
🇪🇸
Madrid, Spain
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Hospital del Mar, Department of Infectious Diseases
🇪🇸
Barcelona, Spain
University Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski", Sofia, Clinic of Clinical Hematology
🇧🇬
Sofia, Bulgaria
Institute of Infectious Diseases
🇷🇴
Bucharest, Sector 2, Romania
Sfanta Parascheva Parascheva Iasi Clinical Hospital for Infectious Diseases
🇷🇴
Iaşi, Romania
University Hospital Virgen del Rocio (HUVR)
🇪🇸
Sevilla, Spain
University Hospital La Fe
🇪🇸
Valencia, Spain
Hospital Clinic i Provincial de Barcelona, Department of Infectious Diseases
🇪🇸
Barcelona, Catalonia, Spain
University Hospital Clinical San Carlos
🇪🇸
Madrid, Spain
University Hospital Virgen Macarena
🇪🇸
Sevilla, Spain
University Hospital Nuestra Senora de Valme,
🇪🇸
Sevilla, Spain
Augusta University
🇺🇸
Augusta, Georgia, United States
William Beaumont Hospital
🇺🇸
Royal Oak, Michigan, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Mercury Street Medical
🇺🇸
Butte, Montana, United States
Albany Medical Center
🇺🇸
Albany, New York, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
Mercy Health - St. Vincent Medical Center - ID Clinical Research
🇺🇸
Toledo, Ohio, United States
Erasme Hospital
🇧🇪
Brussels, Belgium
University Hospital Brussels
🇧🇪
Jette, Belgium
Toronto General Hospital-University Health Network
🇨🇦
Toronto, Ontario, Canada
CIUSSS de L'Est-de-l'Île-De-Montréal, Installation Hôpital
🇨🇦
Montréal, Quebec, Canada
McGill University Health Centre-Research Institute
🇨🇦
Montréal, 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
Territorial Clinical Hospital
🇷🇺
Krasnoyarsk, Russian Federation
University of Miami Miller School of Medicine
🇺🇸
Miami, Florida, United States
University of Texas Health Science Center at Houston
🇺🇸
Houston, Texas, United States
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
Hospital Maggiore University Hospital Ospedali Riuniti of Trieste Dept of ID
🇮🇹
Trieste, Italy
University Polyclinic Agostino Gemelli, Complex Operative Unit of Infectious Diseases 2
🇮🇹
Rome, Italy
University Hospital "Santa Maria della Misericordia" of Udine, Department of Specialist Medicine, Clinic of Infectious Diseases
🇮🇹
Udine, Italy
CHU Sart-Tillman
🇧🇪
Liège, Belgium
Jules Bordet Institute
🇧🇪
Brussels, Belgium
Kuban State Medical University
🇷🇺
Krasnodar, Russian Federation
Henry Dunant Hospital Center
🇬🇷
Athens, Greece
General Hospital of Athens "Evangelismos", Department of Critical Care
🇬🇷
Athens, Greece
Craiova County Emergency Clinical Hospital, ATI Clinic
🇷🇴
Craiova, Dolj County, Romania
CHU Brugman
🇧🇪
Brussels, Belgium
Fejer County St. Gyorgy University Teaching Hospital, Central Department of Anesthesiology and Intensive Care Unit
🇭🇺
Szeged, Hungary
Pius Brinzeu County Emergency Clinical Hospital, Anesthesia and Intensive Care Department (Romania)
🇷🇴
Timişoara, Timis County, Romania
Medical Centre, Hungarian Defence Forces, Central Intensive Care Unit and Anesthesiology Department
🇭🇺
Budapest, Hungary
University Hospital of Larissa, Department of Critical Care Unit
🇬🇷
Thessaloníki, Greece
Mariinskaya City Hospital
🇷🇺
Saint Petersburg, Russian Federation
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
Laiko General Hospital of Athens
🇬🇷
Athens, Greece