Study to Evaluate the Efficacy and Safety of Ibrexafungerp in Patients With Fungal Diseases That Are Refractory to or Intolerant of Standard Antifungal Treatment (FURI)

Open-Label Study to Evaluate the Efficacy and Safety of SCY-078 (Ibrexafungerp) in Patients With Fungal Diseases That Are Refractory to or Intolerant of Standard Antifungal Treatment (FURI)

This is a multicenter, open label, non-comparator, single arm study to evaluate the efficacy and safety of ibrexafungerp (SCY-078) in patients ≥ 18 years of age with a documented fungal disease that has been intolerant or refractory (rIFI) to Standard of Care (SoC) antifungal treatment.

Study Overview

• Status: Completed
• Conditions: Coccidioidomycosis; Invasive Pulmonary Aspergillosis; Allergic Bronchopulmonary Aspergillosis; Histoplasmosis; Chronic Pulmonary Aspergillosis; Blastomycosis; Invasive Candidiasis; Recurrent Vulvovaginal Candidiasis; Mucocutaneous Candidiasis; Other Emerging Fungi
• Intervention / Treatment: Drug: Ibrexafungerp

Detailed Description

This is a multicenter, open label, non-comparator, single arm study to evaluate the efficacy and safety of ibrexafungerp in patients ≥ 18 years of age with a documented invasive and/or severe fungal disease that has been intolerant or refractory (rIFI) to Standard of Care (SoC) antifungal treatment. Patients will be treated with ibrexafungerp for up to 180 days. Treatment beyond 180 days and combination therapy with other antifungal agents may be allowed under special circumstances to be agreed upon by the Investigator and the Sponsor.

Subjects must have a proven or probable fungal disease and meet all study criteria to be considered for enrollment. Eligible subjects must also have documented evidence of failure of, intolerance to, or toxicity related to a currently approved SoC antifungal treatment.

Subjects will also be considered for enrollment if they have an eligible fungal disease and, in the judgement of the investigator, the subject cannot receive approved oral antifungal options (e.g. susceptibility of the organism or risk for drug-drug interactions) and a continued IV antifungal therapy is not desirable or feasible due to clinical or logistical circumstances.

Following a screening visit, there will be up to 15 treatment visits, a follow-up visit and 2 follow-up contacts.

• Study Type: Interventional
• Enrollment (Actual): 233
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Medical University of Graz Department of Internal Medicine, Department of Pulmology, Section for Infectious Disease and Tropical Medicine
  • Innsbruck, Austria, 6020
    • Medical University Innsbruck
• Germany
  • Cologne, Germany, 50937
    • Universitatsklinikum Koln, Klinik I fur Innere Medizin
  • Essen, Germany, 45147
    • Universitätsklinikum Essen, Klinik für Infektiologie
  • Frankfurt, Germany, 60590
    • Universitätsklinikum Frankfurt, Department of Internal Medicine II
  • Leipzig, Germany, 04129
    • Klinikum St. Georg gGmbH Department for Infectious Disease, Tropical Medicine and Nephrology
  • Munich, Germany, 81377
    • LMU Klinikum der Universität München, Medizinische Klinik und Poliklinik III
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525
      • Radboud University Medical Center, Department of Medicine Geert Grooteplein Zuid 8
• Pakistan
  • Karachi, Pakistan, 74800
    • Aga Khan University
• South Africa
  • Pretoria, South Africa, 0002
    • Emmed Research
  • Centurion
    • Lyttelton, Centurion, South Africa, 0154
      • Johese Clinical Research
  • Pretoria
    • Groenkloof, Pretoria, South Africa, 0181
      • Into Research
  • Vereeniging
    • Three Rivers, Vereeniging, South Africa, 1935
      • FCRN Clinical Trial Centre
• Spain
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
• United Kingdom
  • London, United Kingdom, SW17 0RE
    • St. George's University of London
  • Manchester, United Kingdom, M13 9PL
    • The University of Manchester
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0006
      • University of Alabama at Birmingham
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital Midtown
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15203
      • University of Pittsburg Medical Center
  • Texas
    • Dallas, Texas, United States, 75390-8589
      • University of Texas Southwestern Medical Center Dallas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Must have a documented eligible invasive and/or severe fungal disease that is refractory or intolerant to Standard-of-Care treatment
2. Be able to tolerate medication orally or through a nasogastric (NG) tube or percutaneous endoscopic gastrostomy (PEG) tube
3. Be able to understand and sign a written informed consent form (ICF), which must be obtained prior to treatment and any study-related procedures.
4. Be able to understand and sign a consent or authorization form which shall permit the use, disclosure and transfer of the subject's personal health information. (e.g., in the U.S. HIPAA Authorization form).
5. Be able to understand and follow all study-related procedures including study drug administration.
6. Agree to use a medically acceptable method of contraception while receiving protocol-assigned product.

Key Exclusion Criteria:

1. An invasive fungal disease with CNS involvement.
2. Subject has an inappropriately controlled fungal disease source (e.g., persistent catheters that cannot be removed and are likely the source of infection).
3. Subject is hemodynamically unstable, requiring vasopressor medication for blood pressure support.
4. A life expectancy < 30 days.
5. Subject with abnormal liver test parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT) >10 x the upper limit of normal (ULN), and/or total bilirubin > 5 x ULN.
6. Subject is pregnant or lactating.
7. Subject has used an investigational drug within 30 days prior to the baseline visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ibrexafungerp (SCY-078); Ibrexafungerp (SCY-078), 750mg/day orally administered for up to 180 days with loading dose of 1500mg/day (for 2 days) for invasive fungal diseases.	Drug: Ibrexafungerp; Experimental Study Drug; Other Names: SCY-078

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieve a Global Response as Determined by the Data Review Committee (DRC) by Fungal Disease.	The percentage of participants who achieve Global Response (defined as complete or partial response) as determined by the DRC at disease specific timepoints by fungal disease. Global Response is measured by participant survival and overall effect of treatment on the disease. Complete response: Survival, all attributable signs/symptoms (including radiological) resolved and myoclogical eradication of disease; Partial response: Survival, improvement of attributable signs/symptoms (including radiological). Disease specific timepoints: End of Treatment (EoT) for invasive candidiasis, EoT or Day 84 for Chronic Mucocutaneous Candidiasis, Test of Cure (TOC) for Vulvovaginal Candidiasis, EoT or Day 90 for Chronic Pulmonary Aspergillosis, EoT or Day 90 Allergic Bronchopulmonary Aspergillosis and EoT for all other diseases.	Vulvovaginal Candidiasis: Day 17. Chronic Mucocutaneous Candidiasis: EOT up to Day 84. Chronic Pulmonary Aspergillus and Allergic Bronchopulmonary Aspergillosis: EOT up to Day 90. All other diseases: EOT up to Day 180. All Days measured from Baseline.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieve a Global Response as Determined by the Data Review Committee (DRC) by Enrollment Category	The percentage of participants who achieve a Global Response (defined as complete or partial response) as determined by the DRC by enrollment category, at disease specific timepoints. Global Response is measured by participant survival and overall effect of treatment on the disease. Complete response: Survival, all attributable signs/symptoms (including radiological) resolved and myoclogical eradication of disease; Partial response: Survival, improvement of attributable signs/symptoms (including radiological). Disease specific timepoints: End of Treatment (EoT) for invasive candidiasis, EoT or Day 84 for Chronic Mucocutaneous Candidiasis, Test of Cure (TOC) for Vulvovaginal Candidiasis, EoT or Day 90 for Chronic Pulmonary Aspergillosis, EoT or Day 90 Allergic Bronchopulmonary Aspergillosis and EoT for all other diseases. Participants may have been enrolled for more than 1 enrollment reason.	Vulvovaginal Candidiasis: Day 17. Chronic Mucocutaneous Candidiasis: EOT up to Day 84. Chronic Pulmonary Aspergillus and Allergic Bronchopulmonary Aspergillosis: EOT up to Day 90. All other diseases: EOT up to Day 180. All Days measured from Baseline.
Percentage of Participants Who Achieve a Global Response as Determined by the Data Review Committee (DRC) by Disease Category.	The percentage of participants who achieve Global Response (defined as complete or partial response) as determined by the DRC at disease specific timepoints by disease category. Global Response is measured by participant survival and overall effect of treatment on the disease. Complete response: Survival, all attributable signs/symptoms (including radiological) resolved and myoclogical eradication of disease; Partial response: Survival, improvement of attributable signs/symptoms (including radiological). Disease specific timepoints: End of Treatment (EoT) for invasive candidiasis, EoT or Day 84 for Chronic Mucocutaneous Candidiasis, Test of Cure (TOC) for Vulvovaginal Candidiasis, EoT or Day 90 for Chronic Pulmonary Aspergillosis, EoT or Day 90 Allergic Bronchopulmonary Aspergillosis and EoT for all other diseases.	Vulvovaginal Candidiasis: Day 17. Chronic Mucocutaneous Candidiasis: EOT up to Day 84. Chronic Pulmonary Aspergillus and Allergic Bronchopulmonary Aspergillosis: EOT up to Day 90. All other diseases: EOT up to Day 180. All Days measured from Baseline.
Percentage of Participants With a Clinical Response (Based on Signs and Symptoms) by Disease Category	The percentage of participants with a Clinical Response as determined by the DRC at disease specific timepoints, by disease category. Clinical Response: resolution or improvement in attributable symptoms and signs of disease and radiological abnormalities (if applicable) . Disease specific timepoints: End of Treatment (EoT) for invasive candidiasis, EoT or Day 84 for Chronic Mucocutaneous Candidiasis, Test of Cure (TOC) for Vulvovaginal Candidiasis, EoT or Day 90 for Chronic Pulmonary Aspergillosis, EoT or Day 90 Allergic Bronchopulmonary Aspergillosis and EoT for all other diseases. Clinical response was evaluated based on disease signs (including radiological signs) and symptoms.	Vulvovaginal Candidiasis: Day 17. Chronic Mucocutaneous Candidiasis: EOT up to Day 84. Chronic Pulmonary Aspergillus and Allergic Bronchopulmonary Aspergillosis: EOT up to Day 90. All other diseases: EOT up to Day 180. All Days measured from Baseline.
Percentage of Participants With a Clinical Response (Signs and Symptoms) by Disease Category and Pathogen	The percentage of participants with a Clinical Response as determined by the DRC by disease category and by pathogen isolated, at disease specific timepoints. Clinical Response: resolution or improvement in attributable symptoms and signs of disease and radiological abnormalities (if applicable) . Disease specific timepoints: End of Treatment (EoT) for invasive candidiasis, EoT or Day 84 for Chronic Mucocutaneous Candidiasis, Test of Cure (TOC) for Vulvovaginal Candidiasis, EoT or Day 90 for Chronic Pulmonary Aspergillosis, EoT or Day 90 Allergic Bronchopulmonary Aspergillosis and EoT for all other diseases. Clinical response was evaluated based on disease signs (including radiological signs) and symptoms.	Vulvovaginal Candidiasis: Day 17. Chronic Mucocutaneous Candidiasis: EOT up to Day 84. Chronic Pulmonary Aspergillus and Allergic Bronchopulmonary Aspergillosis: EOT up to Day 90. All other diseases: EOT up to Day 180. All Days measured from Baseline.
Percentage of Participants With a Clinical Response (Signs and Symptoms) by Fungal Disease	The percentage of participants with a Clinical Response as determined by the DRC by fungal disease, at disease specific timepoints. Clinical Response: resolution or improvement in attributable symptoms and signs of disease and radiological abnormalities (if applicable) . Disease specific timepoints: End of Treatment (EoT) for invasive candidiasis, EoT or Day 84 for Chronic Mucocutaneous Candidiasis, Test of Cure (TOC) for Vulvovaginal Candidiasis, EoT or Day 90 for Chronic Pulmonary Aspergillosis, EoT or Day 90 Allergic Bronchopulmonary Aspergillosis and EoT for all other diseases. Clinical response was evaluated based on disease signs (including radiological signs) and symptoms.	Vulvovaginal Candidiasis: Day 17. Chronic Mucocutaneous Candidiasis: EOT up to Day 84. Chronic Pulmonary Aspergillus and Allergic Bronchopulmonary Aspergillosis: EOT up to Day 90. All other diseases: EOT up to Day 180. All Days measured from Baseline.
Percentage of Participants With a Clinical Response (Signs and Symptoms) by Enrollment Category	The percentage of participants with a Clinical Response as determined by the DRC by enrollment category, at disease specific timepoints. Clinical Response: resolution or improvement in attributable symptoms and signs of disease and radiological abnormalities (if applicable) . Disease specific timepoints: End of Treatment (EoT) for invasive candidiasis, EoT or Day 84 for Chronic Mucocutaneous Candidiasis, Test of Cure (TOC) for Vulvovaginal Candidiasis, EoT or Day 90 for Chronic Pulmonary Aspergillosis, EoT or Day 90 Allergic Bronchopulmonary Aspergillosis and EoT for all other diseases. Clinical response was evaluated based on disease signs (including radiological signs) and symptoms.	Vulvovaginal Candidiasis: Day 17. Chronic Mucocutaneous Candidiasis: EOT up to Day 84. Chronic Pulmonary Aspergillus and Allergic Bronchopulmonary Aspergillosis: EOT up to Day 90. All other diseases: EOT up to Day 180. All Days measured from Baseline.
Percentage of Participants With a Mycological Response by Disease Category	The percentage of participants with a Mycological Response as determined by the DRC by disease category, at disease specific timepoints. Mycological Response: evidence of eradication or clearance of cultures or reduction of fungal burden, as assessed by a quantitative and validated laboratory marker. Disease specific timepoints: End of Treatment (EoT) for invasive candidiasis, EoT or Day 84 for Chronic Mucocutaneous Candidiasis, Test of Cure (TOC) for Vulvovaginal Candidiasis, EoT or Day 90 for Chronic Pulmonary Aspergillosis, EoT or Day 90 Allergic Bronchopulmonary Aspergillosis and EoT for all other diseases. Mycological response was evaluated based on culture, microscopy and other biomarkers of fungal infection.	Vulvovaginal Candidiasis: Day 17. Chronic Mucocutaneous Candidiasis: EOT up to Day 84. Chronic Pulmonary Aspergillus and Allergic Bronchopulmonary Aspergillosis: EOT up to Day 90. All other diseases: EOT up to Day 180. All Days measured from Baseline.
Percentage of Participants With a Mycological Response by Disease Category and Pathogen	The percentage of participants with a Mycological Response as determined by the DRC by disease category and by pathogen, at disease specific timepoints. Mycological Response: evidence of eradication or clearance of cultures or reduction of fungal burden, as assessed by a quantitative and validated laboratory marker. Disease specific timepoints: End of Treatment (EoT) for invasive candidiasis, EoT or Day 84 for Chronic Mucocutaneous Candidiasis, Test of Cure (TOC) for Vulvovaginal Candidiasis, EoT or Day 90 for Chronic Pulmonary Aspergillosis, EoT or Day 90 Allergic Bronchopulmonary Aspergillosis and EoT for all other diseases. Mycological response was evaluated based on culture, microscopy and other biomarkers of fungal infection.	Vulvovaginal Candidiasis: Day 17. Chronic Mucocutaneous Candidiasis: EOT up to Day 84. Chronic Pulmonary Aspergillus and Allergic Bronchopulmonary Aspergillosis: EOT up to Day 90. All other diseases: EOT up to Day 180. All Days measured from Baseline.
Percentage of Participants With a Mycological Response by Fungal Disease	The percentage of participants with a Mycological Response as determined by the DRC by fungal disease, at disease specific timepoints. Mycological Response: evidence of eradication or clearance of cultures or reduction of fungal burden, as assessed by a quantitative and validated laboratory marker. Disease specific timepoints: End of Treatment (EoT) for invasive candidiasis, EoT or Day 84 for Chronic Mucocutaneous Candidiasis, Test of Cure (TOC) for Vulvovaginal Candidiasis, EoT or Day 90 for Chronic Pulmonary Aspergillosis, EoT or Day 90 Allergic Bronchopulmonary Aspergillosis and EoT for all other diseases. Mycological response was evaluated based on culture, microscopy and other biomarkers of fungal infection.	Vulvovaginal Candidiasis: Day 17. Chronic Mucocutaneous Candidiasis: EOT up to Day 84. Chronic Pulmonary Aspergillus and Allergic Bronchopulmonary Aspergillosis: EOT up to Day 90. All other diseases: EOT up to Day 180. All Days measured from Baseline.
Percentage of Participants With a Mycological Response by Enrollment Category	The percentage of participants with a Mycological Response as determined by the DRC by enrollment category, at disease specific timepoints. Mycological Response: evidence of eradication or clearance of cultures or reduction of fungal burden, as assessed by a quantitative and validated laboratory marker. Disease specific timepoints: End of Treatment (EoT) for invasive candidiasis, EoT or Day 84 for Chronic Mucocutaneous Candidiasis, Test of Cure (TOC) for Vulvovaginal Candidiasis, EoT or Day 90 for Chronic Pulmonary Aspergillosis, EoT or Day 90 Allergic Bronchopulmonary Aspergillosis and EoT for all other diseases. Mycological response was evaluated based on culture, microscopy and other biomarkers of fungal infection.	Vulvovaginal Candidiasis: Day 17. Chronic Mucocutaneous Candidiasis: EOT up to Day 84. Chronic Pulmonary Aspergillus and Allergic Bronchopulmonary Aspergillosis: EOT up to Day 90. All other diseases: EOT up to Day 180. All Days measured from Baseline.
Percentage of Participants With a Recurrence of Baseline Fungal Disease	The percentage of participants with a recurrence of their baseline fungal disease as assessed by the DRC at the 25-Day Follow Up (FU) for Vulvovaginal Candidiasis and at the 6-Week FU for all other diseases as assessed by the DRC. Recurrence is defined as having Global Response at end of treatment or test of cure, but re-emergence of the baseline fungal disease during the post treatment follow-up. Re-emergence is required to be with the same species and involving the same site identified at baseline.	42 days for vulvovaginal candidiasis and 6 weeks after End of Treatment (up to 180 days after treatment start) for all other diseases.
Percentage of Participants Surviving at Day 30 or Day 42	Percentage of participants with invasive candidiasis surviving at Day 30 post-Baseline or percentage of participants with other fungal diseases surviving at Day 42 post-Baseline.	Day 30 post-Baseline for Invasive Candidiasis and Day 42 post-Baseline for all other fungal diseases.
Time to Death From Any Cause	Time to death from any cause in days per Fungal Disease	Six weeks after End of Treatment (EOT). EOT for Vulvovaginal Candidiasis is Day 7, Chronic Mucocutaneous Candidiasis is up to Day 84, Chronic Pulmonary Aspergillus and Allergic Bronchopulmonary Aspergillosis is up to Day 90 and up to Day 180 for other.
Describe Ibrexafungerp Plasma Concentrations	Ibrexafungerp plasma concentrations measured at specified timepoints prior to and after administration of study drug for participants that received the following dose regimen: Day 1 and 2 loading dose - 750mg BID Day 3 onwards - 750mg QD	Day 2 post-dose, Day 3-5 pre-dose, Dat 7-10 pre-dose.

Collaborators and Investigators

• Sponsor: Scynexis, Inc.
• Investigators: Study Director: David Angulo, MD, Sponsor GmbH

Publications and helpful links

General Publications

• Davis MR, Donnelley MA, Thompson GR. Ibrexafungerp: A novel oral glucan synthase inhibitor. Med Mycol. 2020 Jul 1;58(5):579-592. doi: 10.1093/mmy/myz083.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Actual): August 25, 2023
• Study Completion (Actual): August 25, 2023

Study Registration Dates

• First Submitted: February 14, 2017
• First Submitted That Met QC Criteria: February 16, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): November 20, 2024
• Last Update Submitted That Met QC Criteria: October 28, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Invasive Fungal Infections; Urogenital Diseases; Genital Diseases; Pathologic Processes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Immune System Diseases; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Genital Diseases, Female; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Protozoan Infections; Parasitic Diseases; Skin Diseases; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Vulvar Diseases; Lung Diseases, Fungal; Vulvitis; Vaginitis; Dermatomycoses; Vaginal Diseases; Vulvovaginitis; Aspergillosis; Pulmonary Aspergillosis; Invasive Pulmonary Aspergillosis; Mycoses; Candidiasis; Candidiasis, Chronic Mucocutaneous; Candidiasis, Vulvovaginal; Candidiasis, Invasive; Aspergillosis, Allergic Bronchopulmonary; Histoplasmosis; Coccidioidomycosis; Coccidiosis; Blastomycosis; Anti-Infective Agents; Antifungal Agents; Ibrexafungerp
• Other Study ID Numbers: SCY-078-301; 2017-000381-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No