| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Candidemia; invasive candidiasis |
| Кандидемия; инвазивна кандидоза |
|
| E.1.1.1 | Medical condition in easily understood language |
| Candidemia; invasive candidiasis |
| Кандидемия; инвазивна кандидоза |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10060573 |
| E.1.2 | Term | Candidemia |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10064954 |
| E.1.2 | Term | Invasive candidiasis |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objectives of this study are to:
- Evaluate the safety and tolerability of intravenous CD101 (CD101 IV) in the safety population.
- Evaluate overall success (mycological eradication and resolution of systemic signs attributable to
candidemia and/or invasive candidiasis [IC]) of CD101 IV in subjects with candidemia and/or IC at Day 14 (±1 day) in the Microbiological Intent-to-treat (mITT) population. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to:
- Evaluate overall success (mycological eradication and resolution of systemic signs attributable to
candidemia and/or IC) of CD101 IV at Day 5 Day, 28 (±2 days; only for
subjects with IC) and Follow-up (FU, Days 45-52 for subjects with candidemia only or Days 52-59 for
subjects with IC, with or without candidemia) in the mITT population.
- Evaluate mycological success (eradication) of CD101 IV at Day 5, Day 14 (±1 day), Day 28 (±2 days; only for subjects with IC), and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia) in the mITT population.
- Evaluate clinical cure as assessed by the Investigator for CD101 IV at Day 14 (±1 day), Day 28 (±2 days; only for subjects with IC), and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia) in the mITT population.
- Evaluate the pharmacokinetics (PK) of CD101 IV. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects must meet ALL of the following inclusion criteria to be enrolled:
1. Males or females >=18 years.
2. Established mycological diagnosis of candidemia and/or IC from a
sample taken =<96 hours before randomization defined as:
a. >=1 blood culture positive for yeast or Candida
OR
b. Positive test for Candida from a Sponsor-approved rapid IVD
OR
c. Positive Gram stain for yeast or positive culture for Candida spp. from a specimen obtained from a normally sterile site
3. Willing to initiate or continue medical treatment to cure infections,
including receipt of antibiotics and surgical procedures, if required.
sUBJECTS receiving only medications and measures for comfort and not
cure should not be enrolled.
4. Female subjects of child-bearing potential <2 years post-menopausal 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 (e.g., oral contraceptive, implant, injectable, indwelling intrauterine device, vasectomized partner), or sexual abstinence while participating in this study. 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.
5. 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.
6. Presence of one or more systemic signs attributable to candidemia and/or IC (e.g., fever, hypothermia, hypotension, tachycardia, tachypnea). |
|
| E.4 | Principal exclusion criteria |
Subjects must NOT meet any of the following exclusion criteria to be enrolled:
1. Any of the following forms of IC:
a. Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed)
b. Osteomyelitis
c. Endocarditis or myocarditis
d. Meningitis, endophthalmitis, or any central nervous system infection
2. Neutropenia (absolute neutrophil count =<500/mcL) at screening or anticipated neutropenia during the study.
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. Received systemic treatment with an antifungal agent at approved doses for treatment of candidemia or IC for >48 hours (for example, >2 doses of a once daily antifungal agent or >4 doses of a twice daily antifungal agent) in the last 96 hours before randomization.
a.Exception: Receipt of antifungal therapy to which any Candida spp.
isolated at Screening in qualifying cultures is not susceptible.
6. Pregnant females.
7. Lactating females who are nursing.
8. Known hypersensitivity to CD101 IV, caspofungin, any echinocandin, or to any of their excipients
9. Previous participation in this or any previous CD101 study.
10. 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.
11. The Principal Investigator considers that the subject should not participate in the study
12. Presence of an indwelling vascular catheter or device that cannot be removed and is likely to be the
source of candidemia. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy
The primary efficacy end point is overall success at Day 14 (±1 day), as
defined below:
- Mycological eradication defined as:
o If positive blood culture at baseline: 2 negative blood cultures drawn ≥12 hours apart without intervening positive blood cultures
OR
o If positive culture from a normally sterile site (other than blood):
- Documented mycological eradication: most recent culture on or prior to Day 14 (±1 day) from all normally sterile sites of baseline Candida infection (if accessible) is negative
OR
- Presumed mycological eradication: follow-up culture is not available
(eg, normally sterile baseline site of Candida infection not accessible) in
a subject with a successful clinical outcome (ie, did not receive rescue
antifungal treatment and has resolution of systemic signs of IC that
were present at baseline) and resolution or improvement of any baseline
radiographic abnormalities due to IC
AND
• Resolution of attributable systemic signs of candidemia and/or IC that
were present at baseline
AND
•No change of antifungal therapy for the treatment of candidemia
and/or IC
AND
• The subject is not lost to follow up on the day of assessment
AND
- Resolution of systemic signs attributable to candidemia that were
present at baseline |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Secondary efficacy outcome measures include:
- Mycological eradication
- Clinical cure as assessed by the Investigator
Additional efficacy outcome measures include:
- All-cause 30-day mortality
- Time to first of 2 negative blood cultures drawn >=12 hours apart, without an intervening positive culture
Pharmacokinetics (Part A only):
Blood samples will be obtained from subjects to evaluate the PK of CD101 IV. Blood samples will be collected for all 3 treatment groups for the purpose of maintaining the blind, but only PK samples from the CD101 IV groups will be analyzed by a central bioanalytical laboratory.
Safety:
Safety will be assessed from the signing of the informed consent form atScreening to the FU visit through the evaluation of AEs, vital signs
(temperature, heart rate, blood pressure, and respiratory rate), ECGs,
and clinical laboratory data (clinical chemistry panels, hematology
evaluations, and urinalyses). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy assessments will be recorded on Day 5, Day 14 (±1 day),Day 28 (±2 days; only for subjects with IC), and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia).
PK samples will be drawn on day 1, 2, 4, 8 and 15. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 36 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Belgium |
| Bulgaria |
| Canada |
| Greece |
| Hungary |
| Italy |
| Romania |
| Russian Federation |
| Spain |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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