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

• ClinicalTrials.gov Identifier: NCT03672292
• Recruitment Status: Completed
• First Posted: September 14, 2018
• Last Update Posted: March 4, 2024
• Sponsor: Scynexis, Inc.
• Information provided by (Responsible Party): Scynexis, Inc.

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
Invasive Pulmonary Aspergillosis	Drug: SCY-078; Drug: Voriconazole; Other: Oral Placebo Tablets	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 (Clinical Trial)
• Actual Enrollment: 22 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: January 22, 2019
• Actual Primary Completion Date: March 27, 2023
• Actual Study Completion Date: March 27, 2023

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 Name: 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 Name: SCY-078 matching Placebo

Outcome Measures

Primary Outcome Measures :

1. Adverse events; discontinuation due to AE; death [ Time Frame: 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) [ Time Frame: At end of treatment, day 42 and day 84 ]
   Percentage of subjects with Complete Response or Partial Response
2. Death [ Time Frame: At Day 42 and Day 84 ]
   Percentage of subjects who died (any cause)
3. Change in serum GMI [ Time Frame: Weeks 1, 2, 4 and 6 ]
   Absolute and percent change in serum GMI from Baseline
4. Study drug and comparator plasma concentrations [ Time Frame: Through the first 2 weeks of study ]
   SCY-078 and voriconazole plasma concentrations population PK analysis

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Massachusetts

Brigham Womens Hospital INF 75 Francis Street PBB-A4

Boston, Massachusetts, United States, 02115

United States, Michigan

University of Michigan UH south F4005; 1500 E. Medical Center Drive SPC 5378

Ann Arbor, Michigan, United States, 48109

United States, North Carolina

Wake Forest Baptist Medical Center 1 Medical Center Blvd.

Winston-Salem, North Carolina, United States, 27157

Belgium

Hematology Department AZ Sint-Jan Brugge - Oostende AV Campus Brugge Ruddershove 10 8000

Brugge, Belgium

UZ Leuven campus Gasthuisberg Hematology Department Herestraat 49 B - 3000

Leuven, Belgium

Canada, Ontario

University Health Network at the University of Toronto

Toronto, Ontario, Canada, M5G 2C4

Germany

Universitaetsklinikum Koeln, Klinisches Studienzentrum 2 für Infektiologie, Klinik I für Innere Medizin Kerpener Str. 62, Bettenhaus Ebene 15 Raum 64

Köln, Germany, 50937

South Africa

Alberts Cellular Therapy Center (ACT)

Pretoria, Gauteng, South Africa, 0044

Sponsors and Collaborators

Scynexis, Inc.

Investigators

• Study Director: David Angulo, MD; Scynexis, Inc.

More Information

• Responsible Party: Scynexis, Inc.
• ClinicalTrials.gov Identifier: NCT03672292
• Other Study ID Numbers: SCY-078-206; 2018-002565-18 ( EudraCT Number )
• First Posted: September 14, 2018
• Last Update Posted: March 4, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• 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.:

Aspergillosis; SCY-078; Ibrexafungerp; Coadministration

Additional relevant MeSH terms:

Aspergillosis; Pulmonary Aspergillosis; Invasive Pulmonary Aspergillosis; Mycoses; Bacterial Infections and Mycoses; Infections; Lung Diseases, Fungal; Lung Diseases; Respiratory Tract Diseases; Invasive Fungal Infections; Voriconazole; Ibrexafungerp; Antifungal Agents; Anti-Infective Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cytochrome P-450 CYP3A Inhibitors