Evaluate Safety and Efficacy of the Coadministration of Ibrexafungerp With Voriconazole in Patients With Invasive Pulmonary Aspergillosis

NCT03672292 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: SCY-078-2062018-002565-18
• Study Type: interventional
• Target: 22
• Locations: 5 countries
• Sites: 8

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.

Conditions

Invasive Pulmonary Aspergillosis

Keywords

Aspergillosis; SCY-078; Ibrexafungerp; Coadministration

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths

  Number of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), discontinuations due to AEs and deaths.

  Up to a maximum of 19 weeks

Secondary Outcomes (8)

• Percentage of Participants With Complete Response or Partial Response as Determined by the Data Review Committee (DRC)

  At end of treatment (up to 13 weeks), day 42 and day 84

• Percentage of Participants Who Died (Any Cause)

  At Day 42 and Day 84

• Change in Serum Galactomannan Index (GMI)

  Weeks 1, 2, 4 and 6

• Percent of Participants With Changes in GMI

  Weeks 1, 2, 4 and 6 from Baseline

• Time to Achieve Serum GMI Change From Baseline

  Up to a maximum of 19 weeks

Study Arms (2)

SCY-078 plus Voriconazole

EXPERIMENTAL

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; Drug: Voriconazole

Voriconazole mono-therapy

PLACEBO COMPARATOR

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; Other: Oral Placebo Tablets

Interventions

SCY-078 DRUG

Oral tablets of SCY-078

Also known as: Ibrexafungerp

SCY-078 plus Voriconazole

Voriconazole DRUG

Voriconazole IV vials or oral tablets

SCY-078 plus Voriconazole; Voriconazole mono-therapy

Oral Placebo Tablets OTHER

Oral Placebo Tablets matching SCY-078

Also known as: SCY-078 matching Placebo

Voriconazole mono-therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Scynexis, Inc.: lead

Study Sites (8)

Brigham Womens Hospital INF 75 Francis Street PBB-A4

Boston, Massachusetts, 02115, United States

Location

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

Ann Arbor, Michigan, 48109, United States

Location

Wake Forest Baptist Medical Center 1 Medical Center Blvd.

Winston-Salem, North Carolina, 27157, United States

Location

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

Bruges, Belgium

Location

UZ Leuven campus Gasthuisberg Hematology Department Herestraat 49 B - 3000

Leuven, Belgium

Location

University Health Network at the University of Toronto

Toronto, Ontario, M5G 2C4, Canada

Location

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

Cologne, 50937, Germany

Location

Alberts Cellular Therapy Center (ACT)

Pretoria, Gauteng, 0044, South Africa

Location

MeSH Terms

Conditions

Invasive Pulmonary Aspergillosis; Aspergillosis

Interventions

ibrexafungerp; Voriconazole

Condition Hierarchy (Ancestors)

Pulmonary Aspergillosis; Mycoses; Bacterial Infections and Mycoses; Infections; Invasive Fungal Infections; Lung Diseases, Fungal; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: David Angulo
• Organization: Scynexis

David.Angulo@scynexis.com

201-884-5471

Study Officials

• David Angulo, MD

  Scynexis, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2018
• First Posted: September 14, 2018
• Study Start: January 22, 2019
• Primary Completion: March 27, 2023
• Study Completion: March 27, 2023
• Last Updated: August 9, 2024
• Results First Posted: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); CA (1); ZA (1); BE (2); US (3)