Clinical trial NCT03672292: Evaluate Safety and Efficacy of the Coadministration of Ibrexafungerp With Voriconazole in Patients With Invasive Pulmonary Aspergillosis
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Invasive Pulmonary Aspergillosis
Keywords: Aspergillosis
SCY-078
Ibrexafungerp
Coadministration
Lead sponsor: Scynexis, Inc.
Sponsor class: INDUSTRY
First posted: 2018-09-14
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths
timeFrame: Up to a maximum of 19 weeks
Secondary outcomes:
measure: Percentage of Participants With Complete Response or Partial Response as Determined by the Data Review Committee (DRC)
timeFrame: At end of treatment (up to 13 weeks), day 42 and day 84
measure: Percentage of Participants Who Died (Any Cause)
timeFrame: At Day 42 and Day 84
measure: Change in Serum Galactomannan Index (GMI)
timeFrame: Weeks 1, 2, 4 and 6
measure: Percent of Participants With Changes in GMI
timeFrame: Weeks 1, 2, 4 and 6 from Baseline
measure: Time to Achieve Serum GMI Change From Baseline
timeFrame: Up to a maximum of 19 weeks
measure: Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC
timeFrame: End of Treatment (EoT), Day 42 and Day 84
measure: Percentage of Participants With a Clinical, Mycological and Radiological Response.
timeFrame: End of Treatment (EoT), Day 42 and Day 84
measure: SCY-078 and Voriconazole Plasma Concentrations
timeFrame: Treatment Days 7 and 14 (2-4 hrs post dose)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham Womens Hospital INF 75 Francis Street PBB-A4
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan UH south F4005; 1500 E. Medical Center Drive SPC 5378
state: Michigan
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center 1 Medical Center Blvd.
state: North Carolina
city: Brugge
country: Belgium
facility: Hematology Department AZ Sint-Jan Brugge - Oostende AV Campus Brugge Ruddershove 10 8000
city: Leuven
country: Belgium
facility: UZ Leuven campus Gasthuisberg Hematology Department Herestraat 49 B - 3000
city: Toronto
country: Canada
facility: University Health Network at the University of Toronto
state: Ontario
city: Köln
country: Germany
facility: Universitaetsklinikum Koeln, Klinisches Studienzentrum 2 für Infektiologie, Klinik I für Innere Medizin Kerpener Str. 62, Bettenhaus Ebene 15 Raum 64
city: Pretoria
country: South Africa
facility: Alberts Cellular Therapy Center (ACT)
state: Gauteng
Study officials:
affiliation: Scynexis, Inc.
name: David Angulo, MD
role: STUDY_DIRECTOR
References: