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)

• ClinicalTrials.gov Identifier: NCT05178862
• Recruitment Status: Suspended
• First Posted: January 5, 2022
• Last Update Posted: November 18, 2023
• Sponsor: Scynexis, Inc.
• Information provided by (Responsible Party): Scynexis, Inc.

Tracking Information

• First Submitted Date: December 16, 2021
• First Posted Date: January 5, 2022
• Last Update Posted Date: November 18, 2023
• Actual Study Start Date: August 3, 2022
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 14, 2023)

• All-cause mortality (US FDA Only) [ Time Frame: Day 30 ]
  The number and percentage of subjects in each treatment group who are alive and deceased in the ITT population.
• Global Response at End of Treatment (EU European Medicines Agency [EMA] Only) [ Time Frame: Up to 6 weeks ]
  The percentage of subjects with Successful Global Response, as determined by the Data Review Committee

Original Primary Outcome Measures (submitted: December 16, 2021)

All-cause mortality [ Time Frame: 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.

Current Secondary Outcome Measures (submitted: August 14, 2023)

Global Response at Day 14 [ Time Frame: Day 14 ]

The percentage of subjects with Successful Global Response, as determined by the Data Review Committee

Original Secondary Outcome Measures (submitted: December 16, 2021)

Successful Global Response [ Time Frame: 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 3, Randomized, Double-blind Study for Patients With Invasive Candidiasis Treated With IV Echinocandin Followed by Either Oral Ibrexafungerp or Oral Fluconazole
• 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Candidiasis, Invasive
• Candidemia

Intervention

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

  • Caspofungin
  • Micafungin
  • Anidulafungin

Study Arms

• Experimental: IV echinocandin followed by oral ibrexafungerp (SCY-078)
  Interventions:

  • Drug: SCY-078
  • Drug: Echinocandin
• Active Comparator: IV echinocandin followed by oral fluconazole
  Interventions:

  • Drug: Fluconazole
  • Drug: Echinocandin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Suspended
• Estimated Enrollment (submitted: December 16, 2021): 220
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2024
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Bulgaria, Canada, France, Germany, Greece, Israel, Italy, Korea, Republic of, South Africa, Spain, United States

Administrative Information

• NCT Number: NCT05178862
• Other Study ID Numbers: SCY-078-302; MSG-20 ( Other Identifier: Mycoses Study Group (MSGERC) )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Scynexis, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Scynexis, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: David Angulo, MD; Scynexis, Inc.

• PRS Account: Scynexis, Inc.
• Verification Date: November 2023