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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Candidemia, Mycoses, Fungal Infection, Fungemia, Invasive Candidiasis

Intervention / Treatment
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* Drug: CD101
* Drug: Caspofungin
* Drug: Fluconazole
* Drug: intravenous placebo
* Drug: oral placebo


Participation Criteria
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Eligibility Criteria
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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: Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed) Osteomyelitis Endocarditis or myocarditis 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>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<br>* Intravenous antifungal therapy<br>* Other names: CD101 for Injection;Drug: intravenous placebo<br>* normal saline<br>* Other names: placebo infusion;Drug: oral placebo<br>* microcrystalline cellulose<br>* Other names: encapsulated cellulose;|
| Active Comparator: Group 3<br>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<br>* Intravenous antifungal therapy<br>* Other names: Cancidas;Drug: Fluconazole<br>* oral antifungal therapy<br>* Other names: generic fluconazole;Drug: intravenous placebo<br>* normal saline<br>* Other names: placebo infusion;|
| Experimental: Group 2<br>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<br>* Intravenous antifungal therapy<br>* Other names: CD101 for Injection;Drug: intravenous placebo<br>* normal saline<br>* Other names: placebo infusion;Drug: oral placebo<br>* microcrystalline cellulose<br>* Other names: encapsulated cellulose;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mycoses