E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Invasive Pulmonary Aspergillosis |
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E.1.1.1 | Medical condition in easily understood language |
Infection caused by Aspergillus, a common mold (a type of fungus) |
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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 | 10059259 |
E.1.2 | Term | Pulmonary aspergillosis |
E.1.2 | System Organ Class | 100000004862 |
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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 |
To evaluate the safety and tolerability of the coadministration of SCY-078 and voriconazole compared with the coadministration of SCY-078 placebo and voriconazole in the treatment of invasive pulmonary aspergillosis (IPA). |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of the coadministration of SCY-078 and voriconazole compared with that of SCY-078 placebo and voriconazole in the treatment of IPA o based on Global Response as determined by the Data Review Committee (DRC) as determined by the Principal Investigator o based on all-cause mortality (ACM) o based on serum galactomannan index (GMI) decrease o based on clinical response, mycological response and radiological response as determined by the DRC as determined by the Principal Investigator • To evaluate the pharmacokinetics (PK) of SCY-078 and voriconazole |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is a male or female adult ≥18 years of age on the day the study informed consent form (ICF) is signed. 2. Subject has a probable or proven IPA based on the protocol-specified criteria (Section 22.3) that requires antifungal treatment. Note: Subjects with possible IPA may enter the Screening Phase of the study but will only be randomized after meeting criteria for probable or proven IPA. 3. Subject has a result of a serum GMI from a sample obtained within the 96 hours preceding enrollment into the study (Baseline/Treatment Day 1). 4. Subject has one of the following: a. a diagnosis of a hematological malignancy or a myelodysplastic syndrome or aplastic anemia or has undergone hematopoietic cell transplantation, OR b. who either recently resolved or ongoing neutropenia (neutropenia defined as absolute neutrophil count < 0.5 x 109/L [< 500/mm3] for > 10 days), temporally related to the onset of fungal disease OR c. who received treatment with other recognized T-cell immunosuppressants (such as cyclosporine, tacrolimus, monoclonal antibodies or nucleoside analogs) during the past 90 days including solid organ transplant patients OR d. with inherited severe immunodeficiency (e.g. chronic granulomatous disease, severe combined immunodeficiency). 5. Subject has not received more than 4 days (96 hours) of prior mold-active antifungal 12 NOV 2018 CONFIDENTIAL Page 22 therapy for the treatment of the IPA episode in the 7 days preceding enrollment into the study (Baseline/Treatment Day 1). However, subjects who have received more than 4 days but less than 7 days of prior mold-active antifungal therapy for the treatment of the IPA episode in the 7 days preceding enrollment into the study may be enrolled but will require approval from the study medical monitor, who will evaluate each subject on a case-by-case basis. 6. For Subjects who were receiving anti fungal prophylaxis, the IPA episode would, in the investigator´s judgement, be adequately treated with voriconazole. |
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E.4 | Principal exclusion criteria |
1. Subject has a fungal disease with central nervous system involvement suspected at Screening. 2. Subject is receiving, has received or anticipates to be receiving concomitant medications that are listed in the prohibited medication list (Appendix A in full protocol) within the specified washout periods. 3. Subject has a Karnofsky score <20. 4. Subject is expected to die from a non-infectious cause within 30 days from the day the study ICF is signed. 5. Subject is under mechanical ventilation. 6. Subject has abnormal liver test parameters: AST or ALT >10 x ULN and/or total bilirubin >5 x ULN. Note: Subjects with unconjugated hyperbilirubinemia ( <7 mg/dL ) with a diagnosis of Gilbert’s disease are not excluded. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Frequency of treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), discontinuations due to AEs and deaths. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Global Response as measured by: o Percentage of subjects with Complete Response or Partial Response at EoT (key secondary endpoint), Day 42 and Day 84, as determined by the DRC o Percentage of subjects with Complete Response or Partial Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator • Overall survival, defined as the time from randomization to time of death up to Day 84 • Percentage of subjects who died (any cause) at Days 42 and 84 • Absolute reduction and percent change in serum GMI from Baseline to Weeks 1, 2, 4 and 6 • Percentage of subjects with the following changes in serum GMI from Baseline: o Fifty percent reduction or greater at Weeks 1, 2, 4 and 6 o Twenty-five percent reduction or greater at Weeks 1, 2, 4 and 6 o Any percent reduction at Weeks 1, 2, 4 and 6 o Reduction equal to or greater than 0.25 at Weeks 1, 2, 4 and 6 o Reduction to < 0.5 at Weeks 1, 2, 4 and 6 • Time to achieve the following changes in serum GMI from Baseline: o Fifty percent reduction o Twenty-five percent reduction o Any percent reduction o Reduction equal to or greater than 0.25 o Reduction to < 0.5 in 2 consecutive samples • Percentage of subjects with: o Clinical Response at EoT, Day 42 and Day 84, as determined by the DRC o Mycological Response at EoT, Day 42 and Day 84, as determined by the DRC o Radiological Response at EoT, Day 42 and Day 84, as determined by the DRC • Percentage of subjects with: o Clinical Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator o Mycological Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator o Radiological Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator • SCY-078 and voriconazole plasma concentrations population PK analysis |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoint is included in the relevant endpoint |
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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 | 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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
United States |
Belgium |
Germany |
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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
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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 |
E.8.9.2 | In all countries concerned by the trial months | 3 |