Study to Evaluate the Efficacy and Safety of Ibrexafungerp in Patients With Fungal Diseases That Are Refractory to or Intolerant of Standard Antifungal Treatment
- Conditions
- Invasive CandidiasisAllergic Bronchopulmonary AspergillosisChronic Pulmonary AspergillosisMucocutaneous CandidiasisCoccidioidomycosisBlastomycosisOther Emerging FungiHistoplasmosisInvasive Pulmonary AspergillosisRecurrent Vulvovaginal Candidiasis
- Interventions
- Registration Number
- NCT03059992
- Lead Sponsor
- Scynexis, Inc.
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 233
- Must have a documented eligible invasive and/or severe fungal disease that is refractory or intolerant to Standard-of-Care treatment
- Be able to tolerate medication orally or through a nasogastric (NG) tube or percutaneous endoscopic gastrostomy (PEG) tube
- Be able to understand and sign a written informed consent form (ICF), which must be obtained prior to treatment and any study-related procedures.
- 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).
- Be able to understand and follow all study-related procedures including study drug administration.
- Agree to use a medically acceptable method of contraception while receiving protocol-assigned product.
Key
- An invasive fungal disease with CNS involvement.
- Subject has an inappropriately controlled fungal disease source (e.g., persistent catheters that cannot be removed and are likely the source of infection).
- Subject is hemodynamically unstable, requiring vasopressor medication for blood pressure support.
- A life expectancy < 30 days.
- 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.
- Subject is pregnant or lactating.
- Subject has used an investigational drug within 30 days prior to the baseline visit.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ibrexafungerp (SCY-078) Ibrexafungerp 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Achieve a Global Response as Determined by the Data Review Committee (DRC) by Fungal Disease. 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. 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Achieve a Global Response as Determined by the Data Review Committee (DRC) by Enrollment Category 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. 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.Percentage of Participants Who Achieve a Global Response as Determined by the Data Review Committee (DRC) by Disease Category. 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. 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.Percentage of Participants With a Clinical Response (Based on Signs and Symptoms) by Disease Category 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. 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.Percentage of Participants With a Clinical Response (Signs and Symptoms) by Disease Category and Pathogen 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. 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.Percentage of Participants With a Clinical Response (Signs and Symptoms) by Fungal Disease 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. 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.Percentage of Participants With a Clinical Response (Signs and Symptoms) by Enrollment Category 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. 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.Percentage of Participants With a Mycological Response by Disease Category 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. 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.Percentage of Participants With a Mycological Response by Disease Category and Pathogen 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. 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.Percentage of Participants With a Mycological Response by Fungal Disease 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. 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.Percentage of Participants With a Mycological Response by Enrollment Category 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. 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.Percentage of Participants With a Recurrence of Baseline Fungal Disease 42 days for vulvovaginal candidiasis and 6 weeks after End of Treatment (up to 180 days after treatment start) for all other diseases. 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.
Percentage of Participants Surviving at Day 30 or Day 42 Day 30 post-Baseline for Invasive Candidiasis and Day 42 post-Baseline for all other fungal diseases. 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.
Time to Death From Any Cause 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. Time to death from any cause in days per Fungal Disease
Describe Ibrexafungerp Plasma Concentrations Day 2 post-dose, Day 3-5 pre-dose, Dat 7-10 pre-dose. 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
Trial Locations
- Locations (37)
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University of Pittsburg Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
University of Texas Southwestern Medical Center Dallas
🇺🇸Dallas, Texas, United States
Medical University of Graz Department of Internal Medicine, Department of Pulmology, Section for Infectious Disease and Tropical Medicine
🇦🇹Graz, Austria
Universitätsklinikum Frankfurt, Department of Internal Medicine II
🇩🇪Frankfurt, Germany
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Universitätsklinikum Essen, Klinik für Infektiologie
🇩🇪Essen, Germany
Universitätsklinikum Köln, Klinik I für Innere Medizin
🇩🇪Cologne, Germany
LMU Klinikum der Universität München, Medizinische Klinik und Poliklinik III
🇩🇪Munich, Germany
Klinikum St. Georg gGmbH Department for Infectious Disease, Tropical Medicine and Nephrology
🇩🇪Leipzig, Germany
Johese Clinical Research
🇿🇦Lyttelton, Centurion, South Africa
Into Research
🇿🇦Groenkloof, Pretoria, South Africa
Emmed Research
🇿🇦Pretoria, South Africa
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
FCRN Clinical Trial Centre
🇿🇦Three Rivers, Vereeniging, South Africa
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
St. George's University of London
🇬🇧London, United Kingdom
The University of Manchester
🇬🇧Manchester, United Kingdom
Augusta University
🇺🇸Augusta, Georgia, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Radboud University Medical Center, Department of Medicine Geert Grooteplein Zuid 8
🇳🇱Nijmegen, Gelderland, Netherlands
Medical University Innsbruck
🇦🇹Innsbruck, Austria
Aga Khan University
🇵🇰Karachi, Pakistan
Weill Cornell Medical College
🇺🇸New York, New York, United States