A Phase 3, Randomized, Double-blind Study for Patients With Invasive Candidiasis Treated With IV Echinocandin Followed by Either Oral Ibrexafungerp or Oral Fluconazole

Candidemia Clinical Trial

— MARIO  

Official title:

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)

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05178862
• Other study ID #: SCY-078-302
• Secondary ID: MSG-20
• Status: Suspended
• Phase: Phase 3
• Start date: August 3, 2022
• Est. completion date: August 2024

Study information

• Verified date: November 2023
• Source: Scynexis, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 220
• Est. completion date: August 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• 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).

Key Exclusion Criteria:

• 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.

• Baseline QTcF = 500 msec.

Related Conditions & MeSH terms

• Candidemia
• Candidiasis
• Candidiasis, Invasive

Intervention

Drug:
• SCY-078
Oral ibrexafungerp (SCY-078) as step-down therapy.
• Fluconazole
Oral fluconazole (SCY-078) as step-down therapy.
• Echinocandin
Intravenous echinocandin

Locations

Country	Name	City	State
Belgium	Saint Luc University Hospital	Brussels
Belgium	University Hospital Ghent	Ghent
Belgium	University Hospitals Leuven, Campus Gasthuisberg	Leuven
Bulgaria	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
Canada	McGill University Health Centre	Montréal	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	University Health Network- Toronto General Hospital	Toronto	Ontario
France	Victor Dupouy Hospital Center Argenteuil	Argenteuil
France	Nantes University Hospital Center	Nantes
France	Paris University Hospitals Center- Cochin Hospital	Paris
France	Saint-Louis Hospital	Paris
France	University Hospital Center of Poitiers	Poitiers
Germany	University Hospital Cologne	Cologne
Germany	Frankfurt University Clinic	Frankfurt
Germany	University Hospital Freiburg	Freiburg	Baden-Wuerttemberg
Germany	Univeristy Hospital Jena	Jena	Thuringia
Germany	Municipal Hospital Munich GMbH/Hospital Neuperlach	Munich
Germany	Helios Clinic Wuppertal	Wuppertal
Greece	General Hospital of Athens "Evangelismos"	Athens
Greece	General Hospital of Athens "Evangelismos", 1st Department of Critical Care	Athens
Greece	LAIKO General Hospital	Athens
Greece	University General Hospital "Attikon"	Athens
Greece	General Hospital of Thessaloniki "Ippokratio"	Thessaloníki
Israel	Lady Davis Carmel Medical Center, Infectious Diseases Unit	Haifa
Israel	Rambam Health Care Campus, Institute of Infectious Diseases	Haifa
Israel	Chaim Sheba Medical Center	Tel HaShomer
Italy	IRCCS- University Hospital San Martino-IST	Genoa	Liguria
Italy	Big Metropolitan Hospital Niguarda Regional Health Authority	Milan
Italy	University Polyclinic Hospital of Modena	Modena
Italy	Central Friuli University Healthcare Company	Udine
Korea, Republic of	Keimyung University - Dongsan Medical Center	Daegu
Korea, Republic of	CHA Bundang Medical Center, CHA University	Gyeonggi-do
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Wonju Severance Christian Hospital	Wonju
South Africa	Lakeview Hospital	Benoni	Gauteng
South Africa	Life Groenkloof Hospital	Pretoria	Gauteng
South Africa	Netcare Jakaranda Hospital	Pretoria	Gauteng
South Africa	University of Pretoria and Steve Biko Academic Hospital	Pretoria
South Africa	Zuid-Afrikaans Hospital	Pretoria	Gauteng
South Africa	Mediclinic Victoria	Tongaat	KwaZulu-Natal
South Africa	FCRN Clinical Trials Centre	Vereeniging	Gauteng
Spain	Hospital del Mar Medical Research Institute (IMIM)	Barcelona	Catalonia
Spain	General University Hospital Gregorio Maranon	Madrid
Spain	University Hospital de La Princesa	Madrid
Spain	University Hospital Puerta de Hierro Majadahonda	Madrid
Spain	University Hospital Virgen Macarena	Seville	Andalusia
Spain	University and Polytechnic Hospital La Fe	Valencia
Spain	University Clinical Hospital of Valencia	Valencia
United States	University of Michigan Hospital	Ann Arbor	Michigan
United States	Augusta University Medical Center	Augusta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	University of Alabama at Birmingham School of Medicine	Birmingham	Alabama
United States	Mercury Street Medical Group, PLLC	Butte	Montana
United States	University of Chicago	Chicago	Illinois
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	University of Pennsylvania School of Medicine	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	The Miriam Hospital	Providence	Rhode Island
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	UC Davis Medical Center	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	LSU Health Sciences Center	Shreveport	Louisiana
United States	Banner University Medical Center-Tucson	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Scynexis, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Canada,  France,  Germany,  Greece,  Israel,  Italy,  Korea, Republic of,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Global Response at Day 14	The percentage of subjects with Successful Global Response, as determined by the Data Review Committee	Day 14