SCY-078 + Fluconazole or Echinocandin for Invasive Candidiasis

(MARIO Trial)

Not currently recruiting at 113 trial locations

Overseen By Misha Binder

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Scynexis, Inc.

Must be taking: Echinocandins

Must not be taking: Non-echinocandin antifungals

Disqualifiers: Prosthetic joint, Osteomyelitis, Endocarditis, Meningitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two treatment plans for invasive candidiasis, a serious yeast infection that can enter the bloodstream or tissues. Researchers compare treatments that begin with an intravenous medication called echinocandin, followed by either oral fluconazole or a new drug, ibrexafungerp (SCY-078, an experimental treatment). The goal is to determine which combination more effectively treats the infection. Individuals with a confirmed diagnosis of invasive candidiasis, exhibiting symptoms like fever or low blood pressure, may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have received more than 48 hours of non-echinocandin antifungal therapy recently, you may not be eligible.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ibrexafungerp was well-tolerated in past studies. In one study, patients with invasive candidiasis took 750 mg daily, and this dose was well-tolerated, meaning patients did not experience major side effects.

Fluconazole, already approved by the FDA for treating various fungal infections, has a well-known safety profile. Its widespread use has led to a thorough understanding of its side effects.

In both cases, research indicates that these treatments are generally safe for patients. While all medications can have side effects, these findings suggest that ibrexafungerp and fluconazole have a favorable safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ibrexafungerp (SCY-078) for invasive candidiasis because it offers a new oral treatment option that could complement or replace the standard intravenous echinocandin therapy. Unlike traditional treatments, ibrexafungerp is a triterpenoid antifungal, providing a novel mechanism of action that targets the fungal cell wall differently, potentially reducing resistance issues seen with other antifungals. Additionally, its oral formulation allows for more convenient dosing and could improve patient compliance compared to the more cumbersome IV treatments.

What evidence suggests that this trial's treatments could be effective for invasive candidiasis?

Research has shown that echinocandins effectively treat invasive candidiasis, a serious fungal infection. They prevent the fungus from building its protective outer layer, essential for growth and survival. In this trial, one group of participants will receive an IV echinocandin followed by oral fluconazole, while another group will receive an IV echinocandin followed by oral ibrexafungerp (SCY-078). Studies have found that ibrexafungerp, a newer antifungal pill, effectively combats Candida infections. In some lab studies, ibrexafungerp demonstrated strong action against different types of Candida. In earlier patient studies, those treated with ibrexafungerp showed positive results against invasive candidiasis. Both treatments in this trial aim to fight this infection, offering potential options for patients. ^{3 4 5 6 7}

Who Is on the Research Team?

David Angulo, MD

Principal Investigator

Scynexis, Inc.

Are You a Good Fit for This Trial?

This trial is for patients with invasive candidiasis, including candidemia, confirmed by a recent sterile site culture. Participants must show related symptoms like fever or hypotension. Excluded are those with certain types of infections (like endocarditis), unresolved urinary blockages, concurrent fungal infections other than Candida, previous antifungal treatment failure, severe liver issues, or an uncontrolled source of the infection.

Inclusion Criteria

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).

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. Exception: Receipt of antifungal therapy to which any Candida spp. isolated in qualifying culture is not susceptible., Baseline QTcF ≥ 500 msec.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous echinocandin followed by either oral ibrexafungerp or oral fluconazole

Up to 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Echinocandin
• Fluconazole
• Ibrexafungerp

Trial Overview The study compares two treatments after initial IV echinocandin: oral ibrexafungerp (SCY-078) versus oral fluconazole for invasive candidiasis and candidemia. It's a multicenter trial where participants are randomly assigned to one of the two drug regimens in a double-blind setup.

How Is the Trial Designed?

Group I: IV echinocandin followed by oral ibrexafungerp (SCY-078) Experimental Treatment 2 Interventions

Group II: IV echinocandin followed by oral fluconazole Active Control 2 Interventions

Who Is Running the Clinical Trial?

Scynexis, Inc.

Lead Sponsor

Trials

18

Recruited

2,500+

Citations

1. scynexis.com scynexis.com/wp-content/uploads/2022/12/2022-04-ECCMID-Outcomes-of-Oral-Ibrexafungerp.pdf

Outcomes of Oral Ibrexafungerp in the Treatment of 18 ... Outcome data from DRC assessments are reported here. ... Eighteen patients (mean age 58.3 years, 11 males and 7 females) were determined to have invasive ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9149255/

In Vitro Antifungal Activity of Ibrexafungerp (SCY-078) ... Summary of ibrexafungerp and comparators' in vitro antifungal activities against blood isolates from medically relevant species of Candida.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02244606

Oral Ibrexafungerp (SCY-078) vs Standard-of-Care ... The purpose of this study is to compare the safety, pharmacokinetics, and efficacy of oral SCY-078 vs. standard-of-care following initial intravenous ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31304536/

MSG-10: a Phase 2 study of oral ibrexafungerp (SCY-078) ... Conclusions: The oral ibrexafungerp dose estimated to achieve the target exposure in subjects with invasive candidiasis is 750 mg daily.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666517424000270

Ibrexafungerp: A narrative overview In vivo, IBX was found to be effective in murine models of invasive candidiasis (IC) and invasive pulmonary aspergillosis (IPA). It also showed promising ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03059992

NCT03059992 | Study to Evaluate the Efficacy and Safety ... This is a multicenter, open label, non-comparator, single arm study to evaluate the efficacy and safety of ibrexafungerp (SCY-078) in patients ≥ 18 years of age

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12447529/

Ibrexafungerp: Mechanism of Action, Clinical, and ... Key clinical trials have shown that ibrexafungerp is effective and safe for the indicated patient populations. Further research is needed to ...