SCYNERGIA: Study to Evaluate the Safety and Efficacy of the Coadministration of Ibrexafungerp (SCY-078) With Voriconazole in Patients With Invasive Pulmonary Aspergillosis

Sponsor
Scynexis, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03672292
Collaborator
(none)
60
23
2
46.1
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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
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

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 22, 2019
Anticipated Primary Completion Date :
Oct 14, 2022
Anticipated Study Completion Date :
Nov 26, 2022

Arms and Interventions

Arm Intervention/Treatment
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:
  • Ibrexafungerp
  • 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:
  • SCY-078 matching Placebo
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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

    2. Death [At Day 42 and Day 84]

      Percentage of subjects who died (any cause)

    3. Change in serum GMI [Weeks 1, 2, 4 and 6]

      Absolute and percent change in serum GMI from Baseline

    4. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 a diagnosis of a hematological malignancy or a myelodysplastic syndrome or aplastic anemia or has undergone hematopoietic cell transplantation OR

    5. 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

    6. 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

    7. Subject with inherited severe immunodeficiency (e.g. chronic granulomatous disease, severe combined immunodeficiency)

    8. 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.

    9. 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:
    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 >5 x ULN and/or total bilirubin

    2.5 x ULN.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    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.
    Responsible Party:
    Scynexis, Inc.
    ClinicalTrials.gov Identifier:
    NCT03672292
    Other Study ID Numbers:
    • SCY-078-206
    • 2018-002565-18
    First Posted:
    Sep 14, 2018
    Last Update Posted:
    Jul 22, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Scynexis, Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 22, 2022