SCYNERGIA: Study to Evaluate the Safety and Efficacy of the Coadministration of Ibrexafungerp (SCY-078) With Voriconazole in Patients With Invasive Pulmonary Aspergillosis
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: SCY-078 plus 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 |
Drug: SCY-078
Oral tablets of SCY-078
Other Names:
Drug: Voriconazole
Voriconazole IV vials or oral tablets
|
Placebo Comparator: Voriconazole mono-therapy 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 |
Drug: Voriconazole
Voriconazole IV vials or oral tablets
Other: Oral Placebo Tablets
Oral Placebo Tablets matching SCY-078
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Adverse events; discontinuation due to AE; death [through study completion, an average of 19 weeks]
Frequency of treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), discontinuations due to AEs and deaths.
Secondary Outcome Measures
- Composite clinical, radiological and mycological response (global response) [At end of treatment, day 42 and day 84]
Percentage of subjects with Complete Response or Partial Response
- Death [At Day 42 and Day 84]
Percentage of subjects who died (any cause)
- Change in serum GMI [Weeks 1, 2, 4 and 6]
Absolute and percent change in serum GMI from Baseline
- Study drug and comparator plasma concentrations [Through the first 2 weeks of study]
SCY-078 and voriconazole plasma concentrations population PK analysis
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subject is a male or female adult ≥18 years of age on the day the study informed consent form (ICF) is signed.
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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.
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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).
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Subject has a diagnosis of a hematological malignancy or a myelodysplastic syndrome or aplastic anemia or has undergone hematopoietic cell transplantation OR
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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
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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
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Subject with inherited severe immunodeficiency (e.g. chronic granulomatous disease, severe combined immunodeficiency)
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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.
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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).
Exclusion Criteria:
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Subject has a fungal disease with central nervous system involvement suspected at Screening.
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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.
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Subject has a Karnofsky score <20.
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Subject is expected to die from a non-infectious cause within 30 days from the day the study ICF is signed.
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Subject is under mechanical ventilation.
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Subject has abnormal liver test parameters: AST or ALT >5 x ULN and/or total bilirubin
2.5 x ULN.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | UC Davis Medical Center 4150 V St Ste G500 | Sacramento | California | United States | 95817-1460 |
2 | Emory University Hospital 1364 Clifton Road NE | Atlanta | Georgia | United States | 30322 |
3 | St. Vincent Hospital Indianapolis 8402 Harcourt Rd Suite 806 | Indianapolis | Indiana | United States | 46260 |
4 | Brigham Womens Hospital INF 75 Francis Street PBB-A4 | Boston | Massachusetts | United States | 02115 |
5 | University of Michigan UH south F4005; 1500 E. Medical Center Drive SPC 5378 | Ann Arbor | Michigan | United States | 48109 |
6 | Wayne State University 3990 John R Detroit 48201 Site Supplies/Lab Kits Harper university Hospital 3990 John R # 5904, 5 Hudson | Detroit | Michigan | United States | 48201 |
7 | UNIVERSITY OF MINNESOTA PHYSICIANS Mayo Memorial Building 420 Delaware St SE | Minneapolis | Minnesota | United States | 55455-0341 |
8 | Washington University School of Medicine Division of Infectious Disease 660 S Euclid Ave, Box 8051 | Saint Louis | Missouri | United States | 63110-1010 |
9 | Wake Forest Baptist Medical Center 1 Medical Center Blvd. | Winston-Salem | North Carolina | United States | 27157 |
10 | Lowcountry Infectious Diseases P.A. 1938 Charlie Hall Blvd | Charleston | South Carolina | United States | 29414-5837 |
11 | Memorial Hermann Hospital Texas Medical Center Clinical Research Unit | Houston | Texas | United States | 77030 |
12 | Peter MacCallum Cancer Center, 305 Grattan Street | Melbourne | Australia | 3000 | |
13 | Alfred Hospital, 55 Commercial Road | Melbourne | Australia | 3004 | |
14 | Royal Melbourne Hospital, 300 Grattan Street, Level 9 North | Parkville | Australia | 3050 | |
15 | Hematology Department AZ Sint-Jan Brugge - Oostende AV Campus Brugge Ruddershove 10 8000 | Brugge | Belgium | ||
16 | UZ Leuven campus Gasthuisberg Hematology Department Herestraat 49 B - 3000 | Leuven | Belgium | ||
17 | University Health Network at the University of Toronto | Toronto | Ontario | Canada | M5G 2C4 |
18 | Research Institute of McGill University Health Centre | Montréal | Quebec | Canada | H4A 3J1 |
19 | Universitaetsklinikum Koeln, Klinisches Studienzentrum 2 für Infektiologie, Klinik I für Innere Medizin Kerpener Str. 62, Bettenhaus Ebene 15 Raum 64 | Köln | Germany | 50937 | |
20 | Instituto Nacional de Cancerologia | Mexico City | Tlalpan | Mexico | 14080 |
21 | Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán | Mexico City | Mexico | 14080 | |
22 | Alberts Cellular Therapy Center (ACT) | Pretoria | Gauteng | South Africa | 0044 |
23 | INTO Research | Pretoria | Gauteng | South Africa | 0181 |
Sponsors and Collaborators
- Scynexis, Inc.
Investigators
- Study Director: David Angulo, MD, Scynexis, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SCY-078-206
- 2018-002565-18