| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| INVASIVE CANDIDIA INFECTIONS |
|
| E.1.1.1 | Medical condition in easily understood language |
| Deep tissue candida infections |
|
| 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 | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10064954 |
| E.1.2 | Term | Invasive candidiasis |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 |
• To assess the efficacy of anidulafungin and caspofungin with respect to the
overall global response (clinical and microbiological success) at the EOT in
subjects with a confirmed diagnosis of deep tissue infection due to Candida sp. |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate the safety profile of anidulafungin and of caspofungin in this population;
• To evaluate the clinical and microbiological efficacy of anidulafungin and of caspofungin at various time points. |
|
| 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 eligible for enrollment into the study:
1. Diagnosis of deep tissue Candida infection, defined as follows: growth of Candida sp.from a culture specimen obtained from a normally sterile site, the sample having been taken within 96 hours before study entry or at screening.
The diagnosis will be based on at least one of the following:
a. Positive culture for Candida sp. from a specimen from a normally sterile site with or without a positive blood culture; b. Positive culture for Candida sp. from a drain placed for < 24 hours in a normally sterile site; or c. Any positive blood culture for Candida sp. plus ophthalmic findings consistent with Candida endophthalmitis.
AND
a. At least one of the following:
1. Fever, defined as an oral or tympanic temperature ≥ 38.0°C (100.4°F);
2. Hypothermia, defined as a temperature less than 36.0°C (96.8°F);
3. Systolic blood pressure less than 100 mmHg, or a decrease in systolic blood pressure of at least 30 mmHg from baseline;
4. Signs and/or symptoms of Candida infection;
5. Radiologic findings consistent with Candida infection.
IMPORTANT NOTES:
• Subjects with a high suspicion of Candida infection are eligible for enrollment band study treatment may be instituted, pending culture results. Examples whereby Candida infection may be suspected include, but is not limited to, the following:
• The presence of severe sepsis, sepsis with muscular pain, or sepsis with disseminated skin or mucosal lesions when any of these observations is made during the course of broad spectrum antibiotic therapy or when cultures for bacteria are negative;
• The presence of clinical and/or radiologic signs of deep-seated Candida infection and culture results are either pending or positive for yeast but Candida sp. not yet identified;
• Positive blood culture for yeast but Candida sp. not yet identified.These subjects may be enrolled provided a culture is obtained either at the screening visit (before study treatment is initiated) or within 96 hours prior to study treatment initiation. If culture results are either negative for Candida sp. or not confirmed within 96 hours after enrollment, these subjects will be discontinued from study treatment (but will remain in the study for safety assessment only) and treated according to local standard practices. These subjects will be deemed “non evaluable” and will not be accrued toward the final recruitment goal.
• A positive yeast or Candida culture from urine in the absence of clinical signs and symptoms of pyelonephritis does not qualify as a positive culture for study entry.
•A positive yeast or Candida culture from sputum, bronchoalveolar lavage (BAL) or endotracheal aspirate, or from gastric drainage or aspiration does not qualify for study entry.
2. Male or female ≥ 16 years of age;
3. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally authorized representative) has been informed of all pertinent aspects of the study. Informed assent will be required for children who are not of the local legal age;
4. Subjects who are willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures;
5. Expected hospitalization for at least fourteen (14) days. |
|
| E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the study:
1. Females who are pregnant, lactating (breast feeding) or planning a pregnancy during the course of the study, or who are of childbearing potential and not using an acceptable method of birth control (ie, surgically sterile, intrauterine device, oral contraceptive plus barrier contraceptive, hormone delivery system plus barrier contraceptive or condom in combination with contraceptive cream, jelly or foam). Subjects are to continue contraceptive methods during the study and for at least 30 days after receiving their last treatment;
2. Received prior antifungal treatment with either study drug (anidulafungin or caspofungin) within 30 days prior to enrollment in this study;
3. Ongoing antifungal therapy initiated more then 48 hours prior to enrollment.
IMPORTANT NOTE: Prior azole prophylaxis is allowed;
4. Requiring continued treatment with another systemic antifungal agent. IMPORTANT
NOTE: Use of oral non-absorbable azoles (eg, clotrimazole troches) is permitted;
5. Known to be intolerant to fructose or sucrose.
6. Child-Pugh score >9 or with any of the following abnormal laboratory values:
a. Bilirubin >5 times the upper limit of normal;
b. AST or ALT >10 times the upper limit of normal.
7. Poor venous access that would preclude intravenous drug delivery or multiple blood draws;
8. Known hypersensitivity to echinocandin therapy or to any of the excipients used in the formulation of the study drugs;
9. Participated in a study of an investigational drug or device (without any FDA and EMEA approved indications) within 4 weeks of study entry. The investigational use
of licensed agents is permitted if the subject is on a stable regimen for four weeks prior to study start and expected to remain on the same stable regimen for the duration of this study;
10. Life expectancy < 72 hours;
11. Suspected Candida osteomyelitis, endocarditis, meningitis or any other infections of the central nervous system;
12. Having a prosthetic device and/or vascular catheter (including a central venous catheter or an implantable port) at a suspected site of infection unless the device is removed at study entry or soon after randomization (within 24 – 48 hours).
** Please note ** If it is anticipated that the prosthetic devices or vascular catheter cannot be removed within this time frame, the medical monitor must be contacted to discuss enrollment.
13. Having a prosthetic heart valve or vascular graft suspected to be the site of the Candida infection and positive blood cultures;
14.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• The primary efficacy endpoint is the global response at EOT in the MITT evaluable population. Global response is based on the following definitions:
• Success: clinical AND microbiological success;
• Failure: clinical OR microbiological failure.
Clinical and microbiological assessments will be conducted by the Investigator as described in Section 7: Assessments. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Global response at end of treatment |
|
| E.5.2 | Secondary end point(s) |
• Global response at the 2 week and 6 week FU visits in the MITT population;
• Response based on clinical cure and microbiological success at EOT, and 2 week and 6 week FU visits in the MITT population;
• Clinical response at Day 10;
• Rates of relapse (recurrence) at the 2 week and 6 week FU visits;
• Rates of new infection with an organism not identified at baseline and the 2 week and 6 week FU visits;
• Time to negative blood culture (if subject had a positive blood culture at baseline);
• Safety;
• Time to death;
• All cause mortality during study therapy and FU visits. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 2 and 6 week follow-up visit; clinical response at day 10 will be summarized |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | No |
| 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 | 2 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 19 |
| 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 |
| Croatia |
| Netherlands |
| Portugal |
| Romania |
| Russian Federation |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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 | 9 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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