A PROSPECTIVE, RANDOMIZED TRIAL COMPARING THE SAFETY, TOLERABILITY, AND EFFICACY OF VORICONAZOLE AND ANIDULAFUNGIN IN COMBINATION TO THAT OF VORICONAZOLE ALONE WHEN USED FOR PRIMARY THERAPY OF INVASIVE ASPERGILLOSIS IN PEDIATRIC SUBJECTS AGED 2 TO 17 YEARS

Phase 1

• Conditions: Primary therapy of invasive aspergillosis (IA) in pediatric subjects aged 2 to 17 years.; MedDRA version: 12.1Level: PTClassification code 10003488Term: Aspergillosis

• Registration Number: EUCTR2010-021231-14-NL
• Lead Sponsor: Pfizer Inc. 235 East 42nd Street, New York, NY 10017

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01-13
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. Assent will be required (as applicable) for children per local regulations and for those who, in the investigator’s judgment, are able to comprehend.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Immunocompromised state due to either:
- Receipt of allogeneic hematopoetic stem cell transplantation after myeloablative or non-myeloablative conditioning; or
- Hematologic malignancy (excluding subjects with progressive hematologic disease who have not responded or are not likely to respond to treatment).
4. Diagnosis of proven or probable or possible IA (based on a modified version of the
revised EORTC/MSG consensus definitions).
Proven invasive aspergillosis is defined as:
Histopathologic, cytopathologic, or direct microscopic examination of a needle aspiration or biopsy showing hyphal forms with evidence of associated tissue damage (either microscopically or as an infiltrate or lesion by imaging);
or,
Recovery of Aspergillus species by culture from a sample obtained by a sterile procedure from normally sterile and clinically or radiologically abnormal site consistent with an infectious disease process, excluding BAL, cranial sinus cavity, and urine.
Probable invasive aspergillosis is defined by at least:
- One host factor; and
- One clinical criterion; and
- One microbiologic criterion.
Possible invasive aspergillosis is defined by at least:
- One host factor; and
- One clinical criterion.
5. Male or female from 2 to 17 years of age.
6. Female subjects of childbearing potential must have a negative pregnancy test PLUS adequate contraception as determined by the investigator for the duration of the trial.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects presenting with any of the following will not be included in the study:
1. Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.
2. History of allergy, hypersensitivity, or serious reaction to azole or echinocandin antifungals.
3. Female subjects who are pregnant or lactating.
4. Sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis (ABPA).
5. Chronic IA with duration of symptoms or radiological findings for more than four weeks prior to study entry.
6. Receipt within 24 hours prior to randomization of any of the following medications:
terfenadine, astemizole, cisapride, pimozide, or quinidine (because of the possibility of QT prolongation).
7. Concomitant receipt of any of the following medications: sirolimus, rifampin, rifabutin, carbamazepine, long-acting barbiturates (eg, Phenobarbital, mephobarbital), ritonavir, efavirenz, or ergot alkaloids (eg, ergotamine, dihydroergotamine).
8. Concomitant receipt of drugs with clinically relevant interactions with voriconazole unless closely monitored or dose adjusted.
9. Receipt of systemic antifungal treatment for the current episode of IA for a duration of greater than 96 hours; however, subjects receiving mold-active prophylaxis for greater than 96 hours may be enrolled provided that they meet criteria for proven or probable IA at the time of enrollment.
10. Severe liver dysfunction, defined as total bilirubin, AST, ALT, or alkaline phosphatase >5x upper limit of normal.
11. Moderate or severe renal impairment, with calculated creatinine clearance <50 mL/min. Creatinine clearance will be calculated using the Schwartz formula.
Creatinine Clearance (mL/min) = [k x height (cm)]/serum creatinine (mg/dL)
Where k = 0.55 for children of either sex 12 years of age and less;
k = 0.55 for females 13 to 17 years of age;
k = 0.7 for males 13 to 17 years of age.
12. Mechanical ventilation at the time of enrollment.
13. Previously randomized into this trial.
14. Not expected to survive for at least five days due to the current episode of IA.
15. High likelihood of death due to factors unrelated to aspergillosis (eg, due to relapsed malignancy, severe graft versus host disease, other underlying diseases, etc.) within 30 days following planned enrollment, at the investigator’s discretion.
16. Participation in a study of an investigational drug or device (without any FDA or EMEA approved indications) within four 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 stable regimen for the duration of the trial.
17. 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.
18. Concomitant administration of systemic agents active against Aspergillus species is not permissible during the study treatment period.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified