E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
proven or probable aspergillosis in immunocompromised patients |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003488 |
E.1.2 | Term | Aspergillosis |
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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 |
Endpoints of safety and tolerability are the number of toxicity-related study therapy discontinuations and grade III and IV clinical and laboratory events, as evaluated on the basis of current NCI criteria |
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E.2.2 | Secondary objectives of the trial |
• efficacy of caspofungin in four escalating dosages in the treatment of proven or probable invasive aspergillosis • generate pharmacokinetic parameters for each dosage level |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adults ≥18 years • Immunocompromised due to hematologic malignancies, bone marrow failure syndromes, hematopoietic stem cell transplantation, solid organ transplantation, other conditions resulting in severe neutropenia, HIV infection, prolonged corticosteroid therapy (≥20 mg Prednisone or equivalent for ≥ 3 weeks), treatment with other immunosuppressive medications, or other immunocompromising conditions that place patients at risk for invasive fungal infections (IFIs). • Evidence of proven or probable invasive aspergillosis, by modified EORTC criteria. • • Female patients of childbearing age must have a negative pregnancy test at study entry and take adequate contraceptive measures throughout the study. • Written informed consent given by the patient or his/her legal guardian prior to enrollment in the study.
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E.4 | Principal exclusion criteria |
• Pregnant or breast-feeding female patients. • Patients with the following pathological laboratory findings: o Serum bilirubin > 3x upper limit of the age-adjusted normal range o SGOT or SGPT > 5x the upper limit of the age-adjusted normal range o Alkaline phosphatase > 5x the upper limit of the age-adjusted normal range • Patients who have undergone hematopoietic stem-cell transplantation with clinical or laboratory evidence of active veno-occlusive disease (VOD). VOD is characterized by early elevation of serum transaminases and subsequent persistent elevation of serum bilirubin, tenderness of the liver, increase in body weight, and ascites. • Hemodynamically unstable patients or patients with an expected survival time of <5 days. • Patients previously enrolled in the study. • Patients with concomitant diseases or conditions which, in the opinion of the principle investigator, could distort the results of the study or which could entail an additional risk for a patient receiving the study medication. • Patients concurrently receiving efavirenz, nevirapin, rifampicin, dexamethasone, phenytoin, carbamazepine, phenobarbital or cyclosporin A. Topical use of dexamethasone, e.g. as eye drops, is allowed. • Patients with a documented history of intolerance to echinocandin antifungal agents. • Concomitant other systemic antifungal agents are not permitted on study. • Chronic invasive fungal infection, defined as signs/symptoms of invasive fungal infection present for > 4 weeks preceding entry into study • Prior systemic therapy of ≥ 4 days with any polyene anti-fungal agent within 14 days of study enrollment • Prior systemic therapy of ≥ 4 days with non-polyenes (i.e., azole or echinochandin derivatives) for the current, documented IFI. (Prior systemic anti-fungal therapy with azole derivatives for prophylaxis or as empiric therapy for febrile neutropenia is permissible. Fluconazole is permissible.)
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E.5 End points |
E.5.1 | Primary end point(s) |
Endpoints of safety and tolerability are the number of toxicity-related study therapy discontinuations and grade III and IV clinical and laboratory events, as evaluated on the basis of current NCI criteria |
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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 | Yes |
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
different doses of the same drug |
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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.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
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last visit of the last patient |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |