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

A Phase 2, Multicenter, Randomized, Double-blind Study of the Safety, Tolerability, and Efficacy of Intravenous CD101 vs Intravenous Caspofungin Followed by Oral Fluconazole Step-down in the Treatment of Subjects With Candidemia and/or Invasive Candidiasis

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).

Study Overview

• Status: Completed
• Conditions: Mycoses; Candidemia; Fungemia; Fungal Infection; Invasive Candidiasis
• Intervention / Treatment: Drug: Caspofungin; Drug: CD101; Drug: intravenous placebo; Drug: oral placebo; Drug: 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).

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1070
    • Erasme hospital
  • Brussels, Belgium, 1000
    • Jules Bordet Institute
  • Brussels, Belgium, 1200
    • UCL Saint-Luc
  • Brussels, Belgium, 1020
    • CHU Brugman
  • Gent, Belgium, 9000
    • UZ Gent Algemene Inwendige Zietken
  • Jette, Belgium, 1090
    • University Hospital Brussels
  • Leuven, Belgium, 3000
    • University Hospital Leuven
  • Liège, Belgium, 4000
    • CHU Sart-Tillman
• Bulgaria
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski", Sofia, Clinic of Clinical Hematology
  • Sofia, Bulgaria, 1606
    • University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Burns and Plastic Surgery Clinic, Department of Anesthesiology and Intensive Care
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Juravinski Hospital and Cancer Centre/Hamilton Health Sciences
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital-University Health Network
  • Quebec
    • Montréal, Quebec, Canada, H1T 2M4
      • CIUSSS de L'Est-de-l'Île-De-Montréal, Installation Hôpital
    • Montréal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre-Research Institute
• Greece
  • Athens, Greece, 115 27
    • Laiko General Hospital of Athens
  • Athens, Greece, 11526
    • Henry Dunant Hospital Center
  • Athens, Greece, 10676
    • General Hospital of Athens "Evangelismos", 5th Department of Internal Medicine and Infectious Diseases Unit
  • Athens, Greece
    • General Hospital of Athens "Evangelismos", Department of Critical Care
  • Thessaloníki, Greece, 41110
    • University Hospital of Larissa, Department of Critical Care Unit
  • Chaidari
    • Athens, Chaidari, Greece, 12 462
      • University General Hospital "Attikon", 2nd Department of Critical Care
• Hungary
  • Budapest, Hungary, 1134
    • Medical Centre, Hungarian Defence Forces, Central Intensive Care Unit and Anesthesiology Department
  • Szeged, Hungary, 6725
    • Fejer County St. Gyorgy University Teaching Hospital, Central Department of Anesthesiology and Intensive Care Unit
• Italy
  • Bologna, Italy, 40138
    • Polyclinic S. Orsola-Malpighi, Department of Organ Impairment and Transplants, Operative Unit of Infectious Diseases
  • Modena, Italy, 41124
    • University Polyclinic Hospital of Modena, Department of General and Specialist Surgery, Operative Unit of Anesthesia and Intensive Care I
  • Pisa, Italy, 56124
    • University Hospital of Pisa, Department of Gastroenterology and Infectious Diseases, Operative Unit of Infectious Diseases
  • Rome, Italy, 00168
    • University Polyclinic Agostino Gemelli, Complex Operative Unit of Infectious Diseases 2
  • Trieste, Italy, 34125
    • Hospital Maggiore University Hospital Ospedali Riuniti of Trieste Dept of ID
  • Udine, Italy, 33100
    • University Hospital "Santa Maria della Misericordia" of Udine, Department of Specialist Medicine, Clinic of Infectious Diseases
• Romania
  • Iaşi, Romania, 700116
    • Sfanta Parascheva Parascheva Iasi Clinical Hospital for Infectious Diseases
  • Dolj County
    • Craiova, Dolj County, Romania, 200642
      • Craiova County Emergency Clinical Hospital, ATI Clinic
  • Sector 2
    • Bucharest, Sector 2, Romania, 021105
      • Institute of Infectious Diseases
  • Timis County
    • Timişoara, Timis County, Romania, 300723
      • Pius Brinzeu County Emergency Clinical Hospital, Anesthesia and Intensive Care Department (Romania)
• Russian Federation
  • Krasnodar, Russian Federation, 350063
    • Kuban State Medical University
  • Krasnoyarsk, Russian Federation, 660022
    • Territorial Clinical Hospital
  • Saint Petersburg, Russian Federation, 191104
    • Mariinskaya City Hospital
• Spain
  • Barakaldo, Spain, 48903
    • University Hospital Cruces, Unit of Infectious Diseases
  • Barcelona, Spain, 08003
    • Hospital del Mar, Department of Infectious Diseases
  • Madrid, Spain, 28046
    • University Hospital La Paz
  • Madrid, Spain, 28034
    • University Hospital Ramon y Cajal
  • Madrid, Spain, 28007
    • General University Hospital Gregorio Maranon
  • Madrid, Spain, 28040
    • University Hospital Clinical San Carlos
  • Sevilla, Spain, 41009
    • University Hospital Virgen Macarena
  • Sevilla, Spain, 41014
    • University Hospital Nuestra Senora de Valme,
  • Sevilla, Spain
    • University Hospital Virgen del Rocio (HUVR)
  • Valencia, Spain, 46026
    • University Hospital La Fe
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • University Hospital Vall d'Hebron (HUVH), Department of Infectious Diseases
    • Barcelona, Catalonia, Spain, 08036
      • Hospital Clinic i Provincial de Barcelona, Department of Infectious Diseases
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Davis, California, United States, 95817
      • University of California - Davis
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Detroit, Michigan, United States, 48201
      • Harper University Hospital
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Montana
    • Butte, Montana, United States, 59701
      • Mercury Street Medical
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
  • Ohio
    • Toledo, Ohio, United States, 43608
      • Mercy Health - St. Vincent Medical Center - ID Clinical Research
  • Pennsylvania
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital and Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
  • Virginia
    • Roanoke, Virginia, United States, 24016
      • Virginia Tech, Carillion School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: CD101; Intravenous antifungal therapy; Other Names: CD101 for Injection; Drug: intravenous placebo; normal saline; Other Names: placebo infusion; Drug: oral placebo; microcrystalline cellulose; Other Names: encapsulated cellulose
ACTIVE_COMPARATOR: 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.	Drug: Caspofungin; Intravenous antifungal therapy; Other Names: Cancidas; Drug: intravenous placebo; normal saline; Other Names: placebo infusion; Drug: Fluconazole; oral antifungal therapy; Other Names: generic fluconazole
EXPERIMENTAL: 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.	Drug: CD101; Intravenous antifungal therapy; Other Names: CD101 for Injection; Drug: intravenous placebo; normal saline; Other Names: placebo infusion; Drug: oral placebo; microcrystalline cellulose; Other Names: encapsulated cellulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Emergent Adverse Events [Safety and Tolerability]	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.	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.
Resolution of Systemic Signs Attributable to Candidemia and/or Invasive Candidiasis and Mycological Eradication [Overall Success]	Number of subjects with mycological eradication and complete resolution of all systemic signs of candidemia and/or invasive candidiasis which were present at baseline	Day 14 (± 1 day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mycological Eradication and Resolution of Systemic Signs	Evaluate overall success signs (mycological eradication and resolution of systemic signs attributable to candidemia and/or IC) in the mITT population.	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.
Mycological Eradication	Evaluate mycological success (eradication) in the mITT population.	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)
Clinical Cure	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	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 PK (Cmax)	Evaluate maximum plasma concentration (Cmax) (Part A only)	Day 1, 10 minutes before end of infusion (EOI)
Evaluate PK (Cmin)	Evaluate minimum plasma concentration (Cmin) (Part A only)	Day 8, predose
Evaluate PK (Cmin)	Evaluate minimum plasma concentration (Cmin) (Part A only)	Day 15, predose

Collaborators and Investigators

• Sponsor: Cidara Therapeutics Inc.
• Investigators: Study Director: Taylor Sandison, MD MPH, Cidara Therapeutics

Publications and helpful links

General Publications

• 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. Erratum In: Clin Infect Dis. 2021 Aug 2;73(3):561-562.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 26, 2016
• Primary Completion (ACTUAL): June 1, 2019
• Study Completion (ACTUAL): July 1, 2019

Study Registration Dates

• First Submitted: March 16, 2016
• First Submitted That Met QC Criteria: April 6, 2016
• First Posted (ESTIMATE): April 12, 2016

Study Record Updates

• Last Update Posted (ACTUAL): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 4, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: mycoses
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Sepsis; Invasive Fungal Infections; Candidiasis; Candidemia; Candidiasis, Invasive; Mycoses; Fungemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Caspofungin; Fluconazole; Rezafungin
• Other Study ID Numbers: CD101.IV.2.03; 2015-005599-51 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No