Clinical trial NCT03059992: Study to Evaluate the Efficacy and Safety of Ibrexafungerp in Patients With Fungal Diseases That Are Refractory to or Intolerant of Standard Antifungal Treatment
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Invasive Candidiasis
Mucocutaneous Candidiasis
Coccidioidomycosis
Histoplasmosis
Blastomycosis
Chronic Pulmonary Aspergillosis
Allergic Bronchopulmonary Aspergillosis
Invasive Pulmonary Aspergillosis
Recurrent Vulvovaginal Candidiasis
Other Emerging Fungi
Lead sponsor: Scynexis, Inc.
Sponsor class: INDUSTRY
First posted: 2017-02-23
Enrollment: 233
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label, non-comparator, single arm
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Achieve a Global Response as Determined by the Data Review Committee (DRC) by Fungal Disease.
timeFrame: 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 outcomes:
measure: Percentage of Participants Who Achieve a Global Response as Determined by the Data Review Committee (DRC) by Enrollment Category
timeFrame: 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.
measure: Percentage of Participants Who Achieve a Global Response as Determined by the Data Review Committee (DRC) by Disease Category.
timeFrame: 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.
measure: Percentage of Participants With a Clinical Response (Based on Signs and Symptoms) by Disease Category
timeFrame: 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.
measure: Percentage of Participants With a Clinical Response (Signs and Symptoms) by Disease Category and Pathogen
timeFrame: 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.
measure: Percentage of Participants With a Clinical Response (Signs and Symptoms) by Fungal Disease
timeFrame: 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.
measure: Percentage of Participants With a Clinical Response (Signs and Symptoms) by Enrollment Category
timeFrame: 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.
measure: Percentage of Participants With a Mycological Response by Disease Category
timeFrame: 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.
measure: Percentage of Participants With a Mycological Response by Disease Category and Pathogen
timeFrame: 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.
measure: Percentage of Participants With a Mycological Response by Fungal Disease
timeFrame: 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.
measure: Percentage of Participants With a Mycological Response by Enrollment Category
timeFrame: 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.
measure: Percentage of Participants With a Recurrence of Baseline Fungal Disease
timeFrame: 42 days for vulvovaginal candidiasis and 6 weeks after End of Treatment (up to 180 days after treatment start) for all other diseases.
measure: Percentage of Participants Surviving at Day 30 or Day 42
timeFrame: Day 30 post-Baseline for Invasive Candidiasis and Day 42 post-Baseline for all other fungal diseases.
measure: Time to Death From Any Cause
timeFrame: 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.
measure: Describe Ibrexafungerp Plasma Concentrations
timeFrame: Day 2 post-dose, Day 3-5 pre-dose, Dat 7-10 pre-dose.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburg Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center Dallas
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Graz
country: Austria
facility: Medical University of Graz Department of Internal Medicine, Department of Pulmology, Section for Infectious Disease and Tropical Medicine
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
city: Cologne
country: Germany
facility: Universitätsklinikum Köln, Klinik I für Innere Medizin
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik für Infektiologie
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt, Department of Internal Medicine II
city: Leipzig
country: Germany
facility: Klinikum St. Georg gGmbH Department for Infectious Disease, Tropical Medicine and Nephrology
city: Munich
country: Germany
facility: LMU Klinikum der Universität München, Medizinische Klinik und Poliklinik III
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center, Department of Medicine Geert Grooteplein Zuid 8
state: Gelderland
city: Karachi
country: Pakistan
facility: Aga Khan University
city: Lyttelton
country: South Africa
facility: Johese Clinical Research
state: Centurion
city: Groenkloof
country: South Africa
facility: Into Research
state: Pretoria
city: Three Rivers
country: South Africa
facility: FCRN Clinical Trial Centre
state: Vereeniging
city: Pretoria
country: South Africa
facility: Emmed Research
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: London
country: United Kingdom
facility: St. George's University of London
city: Manchester
country: United Kingdom
facility: The University of Manchester
Study officials:
References:
citation: 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.