Evaluate Safety and Efficacy of the Coadministration of Ibrexafungerp With Voriconazole in Patients With Invasive Pulmonary Aspergillosis
- Conditions
- Invasive Pulmonary Aspergillosis
- Interventions
- Registration Number
- NCT03672292
- Lead Sponsor
- Scynexis, Inc.
- Brief Summary
Study to evaluate the safety and efficacy of coadminstration of SCY-078 with a mold-active azole (voriconazole) compared to voriconazole in patients with invasive pulmonary aspergillosis.
- Detailed Description
This is a multicenter, randomized, double-blind, two-arm study to evaluate the safety, tolerability, efficacy and PK of the coadministration of SCY-078 plus voriconazole compared to those of voriconazole in male and female subjects 18 years of age and older with a probable or proven invasive pulmonary aspergillosis.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 22
- Subject is a male or female adult ≥18 years of age on the day the study informed consent form (ICF) is signed.
- 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.
- 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).
- Subject has a diagnosis of a hematological malignancy or a myelodysplastic syndrome or aplastic anemia or has undergone hematopoietic cell transplantation OR
- Subject 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
- Subject 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
- Subject with inherited severe immunodeficiency (e.g. chronic granulomatous disease, severe combined immunodeficiency)
- Subject has not received more than 4 days (96 hours) of prior mold-active antifungal 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.
- Subject has an IPA episode that, in the investigator´s judgement, requires antifungal therapy and may be adequately treated with voriconazole (i.e., the IPA is not a breakthrough infection while receiving a mold-active azole antifungal [voriconazole, posaconazole, isavuconazole or itraconazole] that requires therapy with a non-azole antifungal agent).
- Subject has a fungal disease with central nervous system involvement suspected at Screening.
- 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.
- Subject has a Karnofsky score <20.
- Subject is expected to die from a non-infectious cause within 30 days from the day the study ICF is signed.
- Subject is under mechanical ventilation.
- Subject has abnormal liver test parameters: AST or ALT >5 x ULN and/or total bilirubin >2.5 x ULN.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SCY-078 plus Voriconazole SCY-078 Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards). PLUS Oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards). Treatment duration = minimum 6 weeks/Max 13 weeks SCY-078 plus Voriconazole Voriconazole Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards). PLUS Oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards). Treatment duration = minimum 6 weeks/Max 13 weeks Voriconazole mono-therapy Oral Placebo Tablets Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards). PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given QD from Day 3 onwards). Treatment duration = minimum 6 weeks/Max 13 weeks Voriconazole mono-therapy Voriconazole Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards). PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given QD from Day 3 onwards). Treatment duration = minimum 6 weeks/Max 13 weeks
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths Up to a maximum of 19 weeks Number of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), discontinuations due to AEs and deaths.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With a Clinical, Mycological and Radiological Response. End of Treatment (EoT), Day 42 and Day 84 Percentage of participants with:
* Clinical Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator
* Mycological Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator
* Radiological Response at EoT, Day 42 and Day 84, as determined by the Principal InvestigatorTime to Achieve Serum GMI Change From Baseline Up to a maximum of 19 weeks Time (days) to achieve the following changes in serum GMI from Baseline:
* Fifty percent reduction
* Twenty-five percent reduction
* Any percent reduction
* Reduction equal to or greater than 0.25Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC End of Treatment (EoT), Day 42 and Day 84 Percentage of participants with:
* Clinical Response at EoT, Day 42 and Day 84, as determined by the DRC
* Mycological Response at EoT, Day 42 and Day 84, as determined by the DRC
* Radiological Response at EoT, Day 42 and Day 84, as determined by the DRCPercentage of Participants With Complete Response or Partial Response as Determined by the Data Review Committee (DRC) At end of treatment (up to 13 weeks), day 42 and day 84 Number and percentage of participants with Complete Response or Partial Response as determined by the Data Review Committee (DRC). Complete Response: Survival and resolution of all attributable symptoms and signs of disease; plus, successful radiological outcome; plus, mycological eradication. Partial Response: Survival and partial resolution of attributable symptoms and signs of disease; plus, improvement (at least 25%) of radiological lesions; plus, mycological eradication.
SCY-078 and Voriconazole Plasma Concentrations Treatment Days 7 and 14 (2-4 hrs post dose) Voriconazole and SCY-078 plasma concentrations (ng/mL)
Percentage of Participants Who Died (Any Cause) At Day 42 and Day 84 Number and Percentage of participants who died (any cause)
Change in Serum Galactomannan Index (GMI) Weeks 1, 2, 4 and 6 Absolute change in serum GMI from from baseline to each time point (Weeks 1, 2, 4 and 6). Negative values indicate a reduction of GMI (i.e., improvement).
Percent of Participants With Changes in GMI Weeks 1, 2, 4 and 6 from Baseline Percentage of participants with the following changes in GMI values from Baseline:
* Fifty percent reduction or greater at Weeks 1, 2, 4 and 6
* Twenty-five percent reduction or greater at Weeks 1, 2, 4 and 6
* Any percent reduction at Weeks 1, 2, 4 and 6
* Reduction equal to or greater than 0.25 at Weeks 1, 2, 4 and 6
* Reduction to \< 0.5 at Weeks 1, 2, 4 and 6
Trial Locations
- Locations (8)
Universitaetsklinikum Koeln, Klinisches Studienzentrum 2 für Infektiologie, Klinik I für Innere Medizin Kerpener Str. 62, Bettenhaus Ebene 15 Raum 64
🇩🇪Köln, Germany
Hematology Department AZ Sint-Jan Brugge - Oostende AV Campus Brugge Ruddershove 10 8000
🇧🇪Brugge, Belgium
University Health Network at the University of Toronto
🇨🇦Toronto, Ontario, Canada
Alberts Cellular Therapy Center (ACT)
🇿🇦Pretoria, Gauteng, South Africa
Brigham Womens Hospital INF 75 Francis Street PBB-A4
🇺🇸Boston, Massachusetts, United States
University of Michigan UH south F4005; 1500 E. Medical Center Drive SPC 5378
🇺🇸Ann Arbor, Michigan, United States
Wake Forest Baptist Medical Center 1 Medical Center Blvd.
🇺🇸Winston-Salem, North Carolina, United States
UZ Leuven campus Gasthuisberg Hematology Department Herestraat 49 B - 3000
🇧🇪Leuven, Belgium