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

• Sponsor: Scynexis, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05178862
• Collaborator: (none)
• Enrollment: 220
• Locations: 12
• Arms: 2
• Anticipated Duration (Months): 18
• Patients Per Site: 18.3
• Patients Per Site Per Month: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Candidiasis, Invasive; Candidemia	Drug: SCY-078; Drug: Fluconazole; Drug: Echinocandin	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 220 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Aug 3, 2022
• Anticipated Primary Completion Date: Jan 1, 2024
• Anticipated Study Completion Date: Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IV echinocandin followed by oral ibrexafungerp (SCY-078)	Drug: SCY-078; Oral ibrexafungerp (SCY-078) as step-down therapy.; Other Names: Ibrexafungerp ; Drug: Echinocandin; Intravenous echinocandin; Other Names: Caspofungin Micafungin Anidulafungin
Active Comparator: IV echinocandin followed by oral fluconazole	Drug: Fluconazole; Oral fluconazole (SCY-078) as step-down therapy.; Other Names: Diflucan ; Drug: Echinocandin; Intravenous echinocandin; Other Names: Caspofungin Micafungin Anidulafungin

Outcome Measures

Primary Outcome Measures

1. All-cause mortality [Day 30]

   Demonstrate IV echinocandin followed by oral ibrexafungerp is non-interior to IV echinocandin followed by fluconazole based on 30-day all-cause mortality.

Secondary Outcome Measures

1. Successful Global Response (clinical, radiological, and mycological response) [Day 14]

   Demonstrate IV echinocandin followed by oral ibrexafungerp is non-interior to IV echinocandin followed by fluconazole based on Global Response at Day 14

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
2	Mercury Street Medical Group, PLLC	Butte	Montana	United States	59701
3	SCYNEXIS, Inc.	Jersey City	New Jersey	United States	07302
4	Rhode Island Hospital	Providence	Rhode Island	United States	02903
5	The Miriam Hospital	Providence	Rhode Island	United States	02906
6	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030
7	Lakeview Hospital	Benoni	Gauteng	South Africa	1500
8	Netcare Jakaranda Hospital	Pretoria	Gauteng	South Africa	0002
9	Zuid-Afrikaans Hospital	Pretoria	Gauteng	South Africa	0002
10	Life Groenkloof Hospital	Pretoria	Gauteng	South Africa	0181
11	FCRN Clinical Trials Centre	Vereeniging	Gauteng	South Africa	1935
12	Mediclinic Victoria	Tongaat	KwaZulu-Natal	South Africa	4400

Sponsors and Collaborators

• Scynexis, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Scynexis, Inc.
• ClinicalTrials.gov Identifier: NCT05178862
• Other Study ID Numbers: SCY-078-302; MSG-20
• First Posted: Jan 5, 2022
• Last Update Posted: Aug 18, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Candidiasis; Candidemia; Candidiasis, Invasive; Fluconazole; Caspofungin; Micafungin; Anidulafungin; Ibrexafungerp; Echinocandins

Study Results

No Results Posted as of Aug 18, 2022