Back to resultsStudy to Evaluate the Safety and Efficacy of the Coadministration of Ibrexafungerp (SCY-078) With Voriconazole in Patients With Invasive Pulmonary Aspergillosis (SCYNERGIA)
Primary Purpose
Invasive Pulmonary Aspergillosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SCY-078
Voriconazole
Oral Placebo Tablets
Sponsored by
About this trial
This is an interventional treatment trial for Invasive Pulmonary Aspergillosis focused on measuring Aspergillosis, SCY-078, Ibrexafungerp, Coadministration
Eligibility Criteria
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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.
Sites / Locations
- UC Davis Medical Center 4150 V St Ste G500
- Emory University Hospital 1364 Clifton Road NE
- St. Vincent Hospital Indianapolis 8402 Harcourt Rd Suite 806
- Brigham Womens Hospital INF 75 Francis Street PBB-A4
- University of Michigan UH south F4005; 1500 E. Medical Center Drive SPC 5378
- Wayne State University 3990 John R Detroit 48201 Site Supplies/Lab Kits Harper university Hospital 3990 John R # 5904, 5 Hudson
- UNIVERSITY OF MINNESOTA PHYSICIANS Mayo Memorial Building 420 Delaware St SE
- Washington University School of Medicine Division of Infectious Disease 660 S Euclid Ave, Box 8051
- Wake Forest Baptist Medical Center 1 Medical Center Blvd.
- Lowcountry Infectious Diseases P.A. 1938 Charlie Hall Blvd
- Memorial Hermann Hospital Texas Medical Center Clinical Research Unit
- Peter MacCallum Cancer Center, 305 Grattan Street
- Alfred Hospital, 55 Commercial Road
- Royal Melbourne Hospital, 300 Grattan Street, Level 9 North
- Hematology Department AZ Sint-Jan Brugge - Oostende AV Campus Brugge Ruddershove 10 8000
- UZ Leuven campus Gasthuisberg Hematology Department Herestraat 49 B - 3000
- University Health Network at the University of Toronto
- Research Institute of McGill University Health Centre
- Universitaetsklinikum Koeln, Klinisches Studienzentrum 2 für Infektiologie, Klinik I für Innere Medizin Kerpener Str. 62, Bettenhaus Ebene 15 Raum 64
- Instituto Nacional de Cancerologia
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
- Alberts Cellular Therapy Center (ACT)
- INTO Research
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
SCY-078 plus Voriconazole
Voriconazole mono-therapy
Arm Description
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
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
Outcomes
Primary Outcome Measures
Adverse events; discontinuation due to AE; death
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)
Percentage of subjects with Complete Response or Partial Response
Death
Percentage of subjects who died (any cause)
Change in serum GMI
Absolute and percent change in serum GMI from Baseline
Study drug and comparator plasma concentrations
SCY-078 and voriconazole plasma concentrations population PK analysis
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03672292
Brief Title
Study to Evaluate the Safety and Efficacy of the Coadministration of Ibrexafungerp (SCY-078) With Voriconazole in Patients With Invasive Pulmonary Aspergillosis
Acronym
SCYNERGIA
Official Title
A Multicenter, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of the Coadministration of SCY-078 With Voriconazole in Patients With Invasive Pulmonary Aspergillosis
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
January 22, 2019 (Actual)
Primary Completion Date
February 14, 2023 (Actual)
Study Completion Date
March 27, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Scynexis, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Invasive Pulmonary Aspergillosis
Keywords
Aspergillosis, SCY-078, Ibrexafungerp, Coadministration
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SCY-078 plus Voriconazole
Arm Type
Experimental
Arm Description
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
Arm Title
Voriconazole mono-therapy
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
SCY-078
Other Intervention Name(s)
Ibrexafungerp
Intervention Description
Oral tablets of SCY-078
Intervention Type
Drug
Intervention Name(s)
Voriconazole
Intervention Description
Voriconazole IV vials or oral tablets
Intervention Type
Other
Intervention Name(s)
Oral Placebo Tablets
Other Intervention Name(s)
SCY-078 matching Placebo
Intervention Description
Oral Placebo Tablets matching SCY-078
Primary Outcome Measure Information:
Title
Adverse events; discontinuation due to AE; death
Description
Frequency of treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), discontinuations due to AEs and deaths.
Time Frame
through study completion, an average of 19 weeks
Secondary Outcome Measure Information:
Title
Composite clinical, radiological and mycological response (global response)
Description
Percentage of subjects with Complete Response or Partial Response
Time Frame
At end of treatment, day 42 and day 84
Title
Death
Description
Percentage of subjects who died (any cause)
Time Frame
At Day 42 and Day 84
Title
Change in serum GMI
Description
Absolute and percent change in serum GMI from Baseline
Time Frame
Weeks 1, 2, 4 and 6
Title
Study drug and comparator plasma concentrations
Description
SCY-078 and voriconazole plasma concentrations population PK analysis
Time Frame
Through the first 2 weeks of study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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).
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Angulo, MD
Organizational Affiliation
Scynexis, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
UC Davis Medical Center 4150 V St Ste G500
City
Sacramento
State/Province
California
ZIP/Postal Code
95817-1460
Country
United States
Facility Name
Emory University Hospital 1364 Clifton Road NE
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
St. Vincent Hospital Indianapolis 8402 Harcourt Rd Suite 806
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Brigham Womens Hospital INF 75 Francis Street PBB-A4
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan UH south F4005; 1500 E. Medical Center Drive SPC 5378
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Wayne State University 3990 John R Detroit 48201 Site Supplies/Lab Kits Harper university Hospital 3990 John R # 5904, 5 Hudson
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
UNIVERSITY OF MINNESOTA PHYSICIANS Mayo Memorial Building 420 Delaware St SE
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455-0341
Country
United States
Facility Name
Washington University School of Medicine Division of Infectious Disease 660 S Euclid Ave, Box 8051
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110-1010
Country
United States
Facility Name
Wake Forest Baptist Medical Center 1 Medical Center Blvd.
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Lowcountry Infectious Diseases P.A. 1938 Charlie Hall Blvd
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29414-5837
Country
United States
Facility Name
Memorial Hermann Hospital Texas Medical Center Clinical Research Unit
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Peter MacCallum Cancer Center, 305 Grattan Street
City
Melbourne
ZIP/Postal Code
3000
Country
Australia
Facility Name
Alfred Hospital, 55 Commercial Road
City
Melbourne
ZIP/Postal Code
3004
Country
Australia
Facility Name
Royal Melbourne Hospital, 300 Grattan Street, Level 9 North
City
Parkville
ZIP/Postal Code
3050
Country
Australia
Facility Name
Hematology Department AZ Sint-Jan Brugge - Oostende AV Campus Brugge Ruddershove 10 8000
City
Brugge
Country
Belgium
Facility Name
UZ Leuven campus Gasthuisberg Hematology Department Herestraat 49 B - 3000
City
Leuven
Country
Belgium
Facility Name
University Health Network at the University of Toronto
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Research Institute of McGill University Health Centre
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Universitaetsklinikum Koeln, Klinisches Studienzentrum 2 für Infektiologie, Klinik I für Innere Medizin Kerpener Str. 62, Bettenhaus Ebene 15 Raum 64
City
Köln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Instituto Nacional de Cancerologia
City
Mexico City
State/Province
Tlalpan
ZIP/Postal Code
14080
Country
Mexico
Facility Name
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
City
Mexico City
ZIP/Postal Code
14080
Country
Mexico
Facility Name
Alberts Cellular Therapy Center (ACT)
City
Pretoria
State/Province
Gauteng
ZIP/Postal Code
0044
Country
South Africa
Facility Name
INTO Research
City
Pretoria
State/Province
Gauteng
ZIP/Postal Code
0181
Country
South Africa
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study to Evaluate the Safety and Efficacy of the Coadministration of Ibrexafungerp (SCY-078) With Voriconazole in Patients With Invasive Pulmonary Aspergillosis
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