A phase III, double-blind, randomized study to evaluate the safety and efficacy of BAL8557 versus a Caspofungin followed by Voriconazole regimen in the treatment of candidemia and other invasive Candida infections.
- Conditions
- Treatment of Candidemia and other invasive Candida infectionsMedDRA version: 17.1Level: LLTClassification code 10060573Term: CandidemiaSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2006-003951-18-HU
- Lead Sponsor
- Astellas Global Pharma Development, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 438
1. Patients and/or legally authorized representative(s), if applicable,
who have been fully informed and have given voluntary written informed consent OR patients unable to write and/or read but who fully understand the oral information given by the Investigator (or nominated representative)who have given oral informed consent witnessed in writing by an independent person. HIPAA authorization for US sites or equivalent privacy language as per national regulations must be obtained.
2. Ability and willingness to comply with the protocol
3. Male and female patients aged = 18 years at the time of signing
informed consent.
4. Female patients must be non-lactating and at no risk of pregnancy for one of the following reasons
- Postmenopausal (amenorrhea for at least 1 year)
- Post-hysterectomy and/or post-bilateral ovariectomy
- If of childbearing potential, having a negative serum or urine human chroonic gonadotrophin (hCG) pregnancy test at screening and is using a highly effective method of birth control throughout the study. Reliable sexual abstinence throughout the course of the study is acceptable as a highly effective method of birth control for the purposes of this study.
5. Patients with candidemia or with an invasive candida infection who have a positive blood or tissue culture obtained within 96 hours prior to randomization, accompanied by related clinical signs and symptoms or histological or cytological changes. Final culture results may still be pending at randomization if histology/cytology reveals yeast.
6. Presence of fever (on one occasion > 38°C oral, or equivalent) or hypothermia (on one occasion <36°C oral, or equivalent) or hypotension (SBP < 100 mmHg or a decrease in SBP of at least 30 mmHg) or appropriate local signs within 96 hours prior to randomization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 270
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 180
1. Women who are pregnant or breastfeeding
2. Known history of allergy, hypersensitivity, or any serious reaction to any of the azole or echinocandin class of antifungal or to any component of the study medication.
3. Patients for whom CAS or VRC is contra-indicated.
4. Patients at high risk for QT/QTc prolongation e.g.
a. Baseline prolongation of QTcF >/= 500 msec
b. Risk factors for Torsade de Pointes (e.g. uncompensated heart failure, abnormal potassium or magnesium levels that cannot be corrected, any unstable cardiac condition during the last 30 days, or a family history of long QT syndrome);
c. The use of concomitant medications that prolong the QT/QTc interval
5. Patients with evidence of persistent moderate to severe hepatic or renal dysfunction with any of the following abnormalities at the time of randomization (may be rechecked using local laboratory):
- Total bilirubin = 3 x upper limit of normal (ULN) OR
- Alanine transaminase or aspartate transaminase = 5 x ULN OR
Patients with known cirrhosis or chronic liver failure OR
- Calculated creatinine clearance < 10 mL/minute OR
- Currently on dialysis or likely to require dialysis during adminstration of study medication.
6. Concomitant use of sirolimus, efavirenz, ritonavir, astemizole,
cisapride, rifampicin/rifampin, rifabutin, ergot alkaloids, long acting barbiturates, carbamazepine, pimozide, quinidine, neostigmine, ketoconazole, valproic acid, St. John's Wort, or terfenadine in the 5 days prior to first administration of study medication.
7. Patients with a sole diagnosis of mucocutaneous candidiasis, i.e.
oropharyngeal, esophageal or genital candidiasis; or candidal lower
urinary tract infection or Candida isolated solely from respiratory tract specimens.
8. Patients with candidemia who failed a previous antifungal therapy for the same infection.
9. Patients with any invasive fungal infection other than candida spp., e.g., cryptococcosis, mould infection or endemic fungal infection.
10. Microbiological (e.g. bacterial infections) findings or other potential conditions that
are temporally related and suggest an alternative etiology of the clinical features in the absence of culture/histology/cytology evidence of systemic Candida infection.
11. Patients who have received systemic antifungal therapy for more than 48 hours within 96 hours prior to the first administration of study medication.
12. Severe prolonged immunosuppression (e.g. chronic granulomatous disease, severe combined immunodeficiency, advanced human immunodeficiency virus infection with CD4 count < 200 or acquired immunodeficiency syndrome-defining condition, severe graft versus host disease [grade III-IV associated with e.g., failure of initial treatment, increased liver enzymes or hypoalbuminaemia]), or any other concomitant medical condition that may impede the accurate assessment of efficacy of study drug treatment.
13. Any known or suspected condition of the patient that may jeopardize adherence to the protocol requirements such as patients with fungal endocarditis, fungal osteomyelitis, fungal meningitis, or with life expectancy of < 30 days.
14. Patients with a concomitant medical condition that, in the opinion of the investigator, may be an unacceptable additional risk to the patient should he/she participates in the study.
15. Patients previously enrolled in a phase III study with isavuconazole.
16. Treatment with any investigational drug in any clinical trial within 30 days
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): Overall response at follow-up 1 (FU1) visit (2 weeks after EOT).;Timepoint(s) of evaluation of this end point: Primary Outcome Measures:<br>•Overall response [ Time Frame: 2 weeks after last study dose ]<br>Resolution of signs and symptoms of infection plus mycological<br>(presumed) eradication;Main Objective: Primary Objective:<br>- To compare safety and efficacy of treatment with isavuconazole (ISA) versus a caspofungin (CAS) ? voriconazole (VRC) regimen in patients with candidemia or other invasive Candida infections.<br>;Secondary Objective: Secondary Objectives:<br>- To compare the effects of treatment on:<br>- Time to first negative blood culture<br>- All-cause Mortality at day 14, End of Treatment (EOT) and all Follow Up visits.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Overall response assessment<br>•Mycological response<br>•Clinical response<br>•Time to first confirmed negative culture<br>•All-cause mortality;Timepoint(s) of evaluation of this end point: •Overall response assessment [ Time Frame: Day 7, end of treatment (up to Day 56), 6 weeks after last study drug ]<br>•Mycological response [ Time Frame: Day 7, end of treatment (up to Day 56), 2 weeks after last study drug, 6 weeks after last study drug ]<br>•Clinical response [ Time Frame: Day 7, end of treatment (up to Day 56),<br>2 weeks after last study drug, 6 weeks after last study drug ]<br>•Time to first confirmed negative culture [ Time Frame: Up to 2 weeks after last study drug ] [ Designated as safety issue: No ]<br>•All-cause mortality [ Time Frame: Day 14, end of treatment (up to Day 56), 2 weeks after last study drug, 6 weeks after last study drug ]