Study Stopped
Termination is not related to safety or efficacy concerns for Ibrexafungerp. GSK's decision is to focus efforts and resources on commercialization of Ibrexafungerp for the already approved VVC and rVVC indications.
A Phase 3, Randomized, Double-blind Study for Patients With Invasive Candidiasis Treated With IV Echinocandin Followed by Either Oral Ibrexafungerp or Oral Fluconazole
MARIO
A Phase 3, Multicenter, Prospective, Randomized, Double-blind Study of Two Treatment Regimens for Candidemia and/or Invasive Candidiasis: Intravenous Echinocandin Followed by Oral Ibrexafungerp Versus Intravenous Echinocandin Followed by Oral Fluconazole (MARIO)
2 other identifiers
interventional
68
13 countries
101
Brief Summary
This is a multicenter, randomized, double-blind study of two treatment regimens for invasive candidiasis included candidemia. Subjects will receive intravenous echinocandin followed by oral ibrexafungerp (SCY-078) vs intravenous echinocandin followed by oral fluconazole.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Aug 2022
Typical duration for phase_3
101 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 16, 2021
CompletedFirst Posted
Study publicly available on registry
January 5, 2022
CompletedStudy Start
First participant enrolled
August 3, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 7, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 16, 2025
CompletedDecember 19, 2025
December 1, 2025
3.3 years
December 16, 2021
December 17, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
All-cause mortality (US FDA Only)
The number and percentage of subjects in each treatment group who are alive and deceased in the ITT population.
Day 30
Global Response at End of Treatment (EU European Medicines Agency [EMA] Only)
The percentage of subjects with Successful Global Response, as determined by the Data Review Committee
Up to 6 weeks
Secondary Outcomes (1)
Global Response at Day 14
Day 14
Study Arms (2)
IV echinocandin followed by oral ibrexafungerp (SCY-078)
EXPERIMENTALIV echinocandin followed by oral fluconazole
ACTIVE COMPARATORInterventions
Oral ibrexafungerp (SCY-078) as step-down therapy.
Oral fluconazole (SCY-078) as step-down therapy.
Intravenous echinocandin
Eligibility Criteria
You may qualify if:
- Subject is a male or female adult ≥ 18 years of age on the day the study informed consent is signed.
- Subject has a diagnosis of candidemia and/or invasive candidiasis, defined as evidence of Candida spp in either a bloodstream or tissue culture from a normally sterile site (excluding eye, cardiac tissue, bone tissue, central nervous system or prosthetic device) collected ≤ 4 days (within 96 hours) prior to initiation of IV echinocandin accompanied by any related clinical signs and/or symptoms (e.g., fever \[on one occasion \> 38°C\], hypotension, or local signs of inflammation).
You may not qualify if:
- Subject has any of the following forms of invasive candidiasis at Screening:
- Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed),
- Osteomyelitis,
- Endocarditis or myocarditis,
- Meningitis, endophthalmitis, or any central nervous system infection,
- Chronic disseminated candidiasis,
- Urinary tract candidiasis due to ascending Candida infection secondary to unresolved obstruction or non-removeable device in the urinary tract,
- Patients with a sole diagnosis of mucocutaneous candidiasis, i.e., oropharyngeal, esophageal, or genital candidiasis; or Candida lower urinary tract infection or Candida isolated solely from respiratory tract specimens,
- Patients with concurrent invasive fungal infection other than Candida spp., e.g., cryptococcosis, mold infection or endemic fungal infection,
- Patients who failed a previous antifungal therapy for the same infection,
- Subject has an inappropriately controlled fungal disease source (e.g., indwelling vascular catheter or device that cannot be removed or an abscess that cannot be drained) that is likely to be the source of the candidemia or invasive candidiasis.
- Subject has abnormal liver test parameters: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels \> 10-fold the upper limit of normal (ULN).
- Subject has severe hepatic impairment and a history of chronic cirrhosis (Child-Pugh score \> 9).
- Subject has received more than 48 hours of non-echinocandin antifungal therapy for the treatment of invasive candidiasis (including candidemia) within 96 hours preceding initiation of IV echinocandin.
- o Exception: Receipt of antifungal therapy to which any Candida spp. isolated in qualifying culture is not susceptible.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Scynexis, Inc.lead
Study Sites (101)
University of Alabama at Birmingham School of Medicine
Birmingham, Alabama, 70121, United States
Banner University Medical Center-Tucson
Tucson, Arizona, 85719, United States
UC Davis Medical Center
Sacramento, California, 95817, United States
UCSF School of Medicine
San Francisco, California, 94143, United States
University of Colorado Anschutz Medical Campus
Denver, Colorado, 80291, United States
Augusta University Medical Center
Augusta, Georgia, 30912, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
Ochsner Medical Center
New Orleans, Louisiana, 70121, United States
LSU Health Sciences Center
Shreveport, Louisiana, 71103, United States
University of Maryland Medical Center
Baltimore, Maryland, 21201, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21287, United States
University of Michigan Hospital
Ann Arbor, Michigan, 48109, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
University of Minnesota Medical Center
Minneapolis, Minnesota, 55455, United States
Mayo Clinic - Rochester
Rochester, Minnesota, 55905, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mercury Street Medical Group, PLLC
Butte, Montana, 59701, United States
Duke University
Durham, North Carolina, 27710, United States
University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15260, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
The Miriam Hospital
Providence, Rhode Island, 02906, United States
Houston Methodist Hospital
Houston, Texas, 77030, United States
University of Texas Health Science Center at Houston
Houston, Texas, 77030, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Saint Luc University Hospital
Brussels, Belgium
University Hospital Ghent
Ghent, Belgium
University Hospitals Leuven, Campus Gasthuisberg
Leuven, Belgium
University Multiprofile Hospital for Active Treatment "Eurohospital Plovdiv", Plovdiv, Department of Surgery
Plovdiv, Bulgaria
University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Clinic of Purulent-Septic Surgery
Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment "Prof. Dr. Stoyan Kirkovich"
Stara Zagora, Bulgaria
Princess Margaret Hospital
Toronto, Ontario, Canada
University Health Network- Toronto General Hospital
Toronto, Ontario, Canada
McGill University Health Centre
Montreal, Quebec, H4A 3J1, Canada
The First Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510080, China
Qingyuan People's Hospital
Qingyuan, Guangdong, 511518, China
The First Affiliated Hospital of Guangzhou Medical University
Guandong, Guangzhou, 510230, China
The First Affiliated Hospital of Jinan University
Guandong, Guangzhou, 510630, China
Nanfang Hospital of Southern Medical University
Guangdong, Guangzhou, 510420, China
The Third Affiliated Hospital Of Sun Yat-Sen University (ZSSY)
Guangdong, Guangzhou, 510630, China
Hainan General Hospital
Haikou, Hainan, 572000, China
Xiangya Hospital, Central South University
Changsha, Hunan, 410008, China
Liuzhou People's Hospital
Liuchow, Liuzhou, 530021, China
Ruijin Hospital
Shanghai, Shanghai Municipality, 200025, China
Huashan Hospital, Institute of Antibiotics
Shanghai, Shanghai Municipality, 200040, China
Shanghai 10th People's Hospital
Shanghai, Shanghai Municipality, 200072, China
West China Hospital, Sichuan University
Chengdu, Sichuan, 610041, China
Chinese Academy of Medical Sciences
Jinghai, Tianjin Municipality, 301617, China
Tianjin Medical University General Hospital
Xiaobailou, Tianjin Municipality, 300052, China
The First Hospital of Kunming
Kunming, Yunnan, 650034, China
The First Affiliated Hospital of Chongqing Medical University
Chongqing, Yuzhong, 400042, China
The first affiliated hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003, China
Zhejiang Provincal Hospital of Chinese Medicine
Hangzhou, Zhejiang, 310006, China
Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
Lishui People's Hospital
Lishui, Zhejiang, 323000, China
Victor Dupouy Hospital Center Argenteuil
Argenteuil, 95107, France
Nantes University Hospital Center
Nantes, 44093, France
Paris University Hospitals Center- Cochin Hospital
Paris, France
Saint-Louis Hospital
Paris, France
University Hospital Center of Poitiers
Poitiers, France
University Hospital Freiburg
Freiburg im Breisgau, Baden-Wurttemberg, Germany
Univeristy Hospital Jena
Jena, Thuringia, Germany
University Hospital Cologne
Cologne, 50937, Germany
Frankfurt University Clinic
Frankfurt, 60596, Germany
Municipal Hospital Munich GMbH/Hospital Neuperlach
Munich, Germany
Helios Clinic Wuppertal
Wuppertal, Germany
General Hospital of Athens "Evangelismos", 1st Department of Critical Care
Athens, Greece
General Hospital of Athens "Evangelismos"
Athens, Greece
LAIKO General Hospital
Athens, Greece
University General Hospital "Attikon"
Athens, Greece
General Hospital of Thessaloniki "Ippokratio"
Thessaloniki, Greece
Lady Davis Carmel Medical Center, Infectious Diseases Unit
Haifa, Israel
Rambam Health Care Campus, Institute of Infectious Diseases
Haifa, Israel
The Tel Aviv Sourasky Medical Center
Tel Aviv, 64239, Israel
Chaim Sheba Medical Center
Tel Litwinsky, Israel
IRCCS- University Hospital San Martino-IST
Genoa, Liguria, 16132, Italy
Big Metropolitan Hospital Niguarda Regional Health Authority
Milan, 20162, Italy
University Polyclinic Hospital of Modena
Modena, 41124, Italy
Central Friuli University Healthcare Company
Udine, Italy
Lakeview Hospital
Benoni, Gauteng, 1500, South Africa
Netcare Jakaranda Hospital
Pretoria, Gauteng, 0002, South Africa
Zuid-Afrikaans Hospital
Pretoria, Gauteng, 0002, South Africa
Life Groenkloof Hospital
Pretoria, Gauteng, 0181, South Africa
FCRN Clinical Trials Centre
Vereeniging, Gauteng, 1935, South Africa
Mediclinic Victoria
Tongaat, KwaZulu-Natal, 4400, South Africa
University of Pretoria and Steve Biko Academic Hospital
Pretoria, South Africa
Keimyung University - Dongsan Medical Center
Daegu, South Korea
CHA Bundang Medical Center, CHA University
Gyeonggi-do, South Korea
Gangnam Severance Hospital
Seoul, South Korea
Severance Hospital, Yonsei University Health System
Seoul, South Korea
Wonju Severance Christian Hospital
Wŏnju, South Korea
University Hospital Virgen Macarena
Seville, Andalusia, Spain
Hospital Clínic de Barcelona
Barcelona, Catalonia, 08036, Spain
Hospital del Mar Medical Research Institute (IMIM)
Barcelona, Catalonia, Spain
University Hospital Ramon y Cajal
Madrid, 28034, Spain
General University Hospital Gregorio Maranon
Madrid, Spain
University Hospital de La Princesa
Madrid, Spain
University Hospital Puerta de Hierro Majadahonda
Madrid, Spain
University and Polytechnic Hospital La Fe
Valencia, Spain
University Clinical Hospital of Valencia
Valencia, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
David Angulo, MD
Scynexis, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 3
- 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
December 16, 2021
First Posted
January 5, 2022
Study Start
August 3, 2022
Primary Completion
November 7, 2025
Study Completion
December 16, 2025
Last Updated
December 19, 2025
Record last verified: 2025-12