Clinical trial NCT05178862: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Candidiasis, Invasive
Candidemia
Lead sponsor: Scynexis, Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-05
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: All-cause mortality (US FDA Only)
timeFrame: Day 30
measure: Global Response at End of Treatment (EU European Medicines Agency [EMA] Only)
timeFrame: Up to 6 weeks
Secondary outcomes:
measure: Global Response at Day 14
timeFrame: Day 14
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham School of Medicine
state: Alabama
city: Tucson
country: United States
facility: Banner University Medical Center-Tucson
state: Arizona
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Shreveport
country: United States
facility: LSU Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Butte
country: United States
facility: Mercury Street Medical Group, PLLC
state: Montana
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania School of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Brussels
country: Belgium
facility: Saint Luc University Hospital
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Leuven
country: Belgium
facility: University Hospitals Leuven, Campus Gasthuisberg
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Eurohospital Plovdiv", Plovdiv, Department of Surgery
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Clinic of Purulent-Septic Surgery
city: Stara Zagora
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Prof. Dr. Stoyan Kirkovich"
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network- Toronto General Hospital
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Argenteuil
country: France
facility: Victor Dupouy Hospital Center Argenteuil
city: Nantes
country: France
facility: Nantes University Hospital Center
city: Paris
country: France
facility: Paris University Hospitals Center- Cochin Hospital
city: Paris
country: France
facility: Saint-Louis Hospital
city: Poitiers
country: France
facility: University Hospital Center of Poitiers
city: Freiburg
country: Germany
facility: University Hospital Freiburg
state: Baden-Wuerttemberg
city: Jena
country: Germany
facility: Univeristy Hospital Jena
state: Thuringia
city: Cologne
country: Germany
facility: University Hospital Cologne
city: Frankfurt
country: Germany
facility: Frankfurt University Clinic
city: Munich
country: Germany
facility: Municipal Hospital Munich GMbH/Hospital Neuperlach
city: Wuppertal
country: Germany
facility: Helios Clinic Wuppertal
city: Athens
country: Greece
facility: General Hospital of Athens "Evangelismos", 1st Department of Critical Care
city: Athens
country: Greece
facility: General Hospital of Athens "Evangelismos"
city: Athens
country: Greece
facility: LAIKO General Hospital
city: Athens
country: Greece
facility: University General Hospital "Attikon"
city: Thessaloníki
country: Greece
facility: General Hospital of Thessaloniki "Ippokratio"
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center, Infectious Diseases Unit
city: Haifa
country: Israel
facility: Rambam Health Care Campus, Institute of Infectious Diseases
city: Tel HaShomer
country: Israel
facility: Chaim Sheba Medical Center
city: Genoa
country: Italy
facility: IRCCS- University Hospital San Martino-IST
state: Liguria
city: Milan
country: Italy
facility: Big Metropolitan Hospital Niguarda Regional Health Authority
city: Modena
country: Italy
facility: University Polyclinic Hospital of Modena
city: Udine
country: Italy
facility: Central Friuli University Healthcare Company
city: Daegu
country: Korea, Republic of
facility: Keimyung University - Dongsan Medical Center
city: Gyeonggi-do
country: Korea, Republic of
facility: CHA Bundang Medical Center, CHA University
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Wŏnju
country: Korea, Republic of
facility: Wonju Severance Christian Hospital
city: Benoni
country: South Africa
facility: Lakeview Hospital
state: Gauteng
city: Pretoria
country: South Africa
facility: Netcare Jakaranda Hospital
state: Gauteng
city: Pretoria
country: South Africa
facility: Zuid-Afrikaans Hospital
state: Gauteng
city: Pretoria
country: South Africa
facility: Life Groenkloof Hospital
state: Gauteng
city: Vereeniging
country: South Africa
facility: FCRN Clinical Trials Centre
state: Gauteng
city: Tongaat
country: South Africa
facility: Mediclinic Victoria
state: KwaZulu-Natal
city: Pretoria
country: South Africa
facility: University of Pretoria and Steve Biko Academic Hospital
city: Seville
country: Spain
facility: University Hospital Virgen Macarena
state: Andalusia
city: Barcelona
country: Spain
facility: Hospital del Mar Medical Research Institute (IMIM)
state: Catalonia
city: Madrid
country: Spain
facility: General University Hospital Gregorio Maranon
city: Madrid
country: Spain
facility: University Hospital de La Princesa
city: Madrid
country: Spain
facility: University Hospital Puerta de Hierro Majadahonda
city: Valencia
country: Spain
facility: University and Polytechnic Hospital La Fe
city: Valencia
country: Spain
facility: University Clinical Hospital of Valencia
Study officials:
affiliation: Scynexis, Inc.
name: David Angulo, MD
role: STUDY_DIRECTOR
References: