Rezafungin for Prevention of Fungal Infections

(ReSPECT Trial)

Recruiting at 45 trial locations

Overseen By Head of Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cidara Therapeutics Inc.

Must not be taking: Antihistamines, Antibiotics, Antifungals, others

Disqualifiers: HIV, Heart failure, Lung function, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 13 weeks

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new drug, Rezafungin (an antifungal medication), is safe and effective in preventing serious fungal infections compared to usual antifungal medications. Participants will receive either Rezafungin through an IV or standard oral antifungal medications. Suitable candidates include those with certain blood-related conditions, such as leukemia or lymphoma, who are receiving a stem cell transplant from a donor. The goal is to enhance protection against infections during this critical period. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking medications that severely interact with the standard antimicrobial regimen, you may need to adjust them. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that Rezafungin for Injection is likely to be safe for humans?

Research has shown that rezafungin is generally safe for people. In studies with adults, it has treated serious fungal infections like candidemia and invasive candidiasis. Although these infections are difficult to treat, the medication was well-tolerated.

One study found that the safety of rezafungin was similar to that of another antifungal drug, caspofungin, meaning patients experienced comparable safety outcomes to existing treatments. Additionally, the FDA has approved rezafungin for treating certain fungal infections, indicating it has passed safety checks for those uses.

While no medication is completely without risk, current research suggests that rezafungin is a safe option for preventing fungal infections in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Rezafungin is unique because it offers a new approach to preventing fungal infections with a convenient once-weekly dosing regimen. Unlike current oral antifungal treatments like fluconazole and posaconazole, which require daily administration, rezafungin is delivered via injection just once a week, potentially improving adherence and outcomes. Researchers are excited about this treatment because it maintains consistent drug levels in the body, which may enhance its effectiveness and reduce the risk of missed doses. This new delivery method could be a game-changer for patients who struggle with daily medication routines.

What evidence suggests that Rezafungin might be an effective treatment for preventing fungal infections?

Research shows that rezafungin, which participants in this trial may receive, holds promise for preventing fungal infections. Studies found that patients treated with rezafungin once a week achieved a 76.1% overall cure rate. This treatment acts quickly to clear infections, demonstrated by high rates of infection removal and negative blood tests. These findings suggest that rezafungin could effectively prevent serious fungal diseases, especially in vulnerable patients like those undergoing bone marrow transplants. The evidence strongly supports rezafungin as an effective option for preventing serious fungal infections. ^{1 2 6 7 8}

Who Is on the Research Team?

Laura Cox, PhD

Principal Investigator

Mundipharma Research Limited

Are You a Good Fit for This Trial?

Adults over 18 with certain blood diseases like leukemia or lymphoma, undergoing bone marrow transplants, can join this trial. They must have good kidney and liver function, agree to birth control measures if applicable, and not have had recent fungal infections or other specific health issues.

Inclusion Criteria

Willing and able to provide written informed consent

I have been diagnosed with a specific blood-related disease.

I agree to use birth control as required by the study.

Exclusion Criteria

Pregnant or lactating females

My lymphoma has not responded to chemotherapy.

I have been diagnosed with heart failure that causes symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Rezafungin or standard antimicrobial regimen for prevention of invasive fungal diseases

13 weeks

Weekly visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Once weekly for outpatient, or twice weekly for inpatient

What Are the Treatments Tested in This Trial?

Interventions

• Rezafungin for Injection

Trial Overview The study is testing Rezafungin's effectiveness in preventing invasive fungal diseases during bone marrow transplantation compared to standard antifungal drugs like Posaconazole and Fluconazole.

How Is the Trial Designed?

Group I: Group 1: Rezafungin for Injection Experimental Treatment 3 Interventions

Subjects in Rezafungin treatment group will receive a 400 mg loading dose in Week 1, followed by 200 mg once weekly, for a total of 13 weeks. Subjects will receive oral placebo for standard antimicrobial regimen (SAR) azole prophylaxis and oral placebo for SAR anti-Pneumocystis pneumonia (PCP) prophylaxis in accordance with the respective SAR dosing regimens for each. For subjects who are switched to a SAR IV regimen, oral placebo for SAR azole prophylaxis will be changed to IV placebo. There is no IV option for SAR anti-PCP prophylaxis.

Group II: Group 2: Oral Antifungal Active Control 3 Interventions

Subjects randomized to the SAR will receive either fluconazole or posaconazole as the first-line SAR as per site's standard practice. Fluconazole will be administered orally at once daily doses of 400 mg for 13 weeks. Posaconazole will be administered orally as 300 mg twice daily on the first day and 300 mg once daily thereafter for 13 weeks. Azole-based antifungal therapy (fluconazole or posaconazole) can be switched from oral therapy to IV therapy if there is oral intolerance, at the discretion of the Investigator. Subjects who started on fluconazole SAR may be switched to posaconazole at the discretion of the Investigator if they develop acute clinically significant GVHD; In addition, subjects in the SAR group will receive anti PCP prophylaxis with oral TMP/SMX (80 mg TMP/ 400 mg SMX) once daily. There is no IV option for SAR anti-PCP prophylaxis.

Rezafungin for Injection is already approved in United States, European Union for the following indications:

Approved in United States as Rezzayo for:

• Candidemia and invasive candidiasis in adults with limited or no alternative treatment options

Approved in European Union as Rezzayo for:

• Treatment of invasive candidiasis in adults

Who Is Running the Clinical Trial?

Cidara Therapeutics Inc.

Lead Sponsor

Trials

12

Recruited

7,400+

Mundipharma Research Limited

Lead Sponsor

Trials

40

Recruited

830,000+

Published Research Related to This Trial

Rezafungin, a new echinocandin drug, shows strong potential as a first-line treatment for invasive fungal infections due to its unique chemical stability and prolonged pharmacokinetics, which allows for easier administration compared to other similar drugs.

In laboratory and animal studies, rezafungin has demonstrated potent activity against a wide range of fungal pathogens, supported by promising results from ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the Novel Echinocandin Antifungal Rezafungin: Animal Studies and Clinical Data. Zhao, Y., Perlin, DS.[2020]

Rezafungin demonstrated non-inferiority to caspofungin in terms of day 30 all-cause mortality rates in patients with candidaemia and invasive candidiasis, with both treatments showing a mortality rate of 19%.

Mycological eradication was achieved more quickly with rezafungin, as 73% of patients showed eradication by day 5 compared to 65% for caspofungin, suggesting a potential early treatment advantage for rezafungin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rezafungin and caspofungin in candidaemia and invasive candidiasis: pooled data from two prospective randomised controlled trials. Thompson, GR., Soriano, A., Honore, PM., et al.[2023]

Rezafungin showed strong in vitro activity against various Aspergillus species, including both wild-type and azole-resistant A. fumigatus isolates, with minimum effective concentrations (MECs) as low as 0.024 mg/L.

It was particularly effective against cryptic Aspergillus species, demonstrating greater potency than caspofungin against A. calidoustus, suggesting it could be a promising treatment option for infections caused by resistant fungal strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rezafungin (CD101) demonstrates potent in vitro activity against Aspergillus, including azole-resistant Aspergillus fumigatus isolates and cryptic species. Wiederhold, NP., Locke, JB., Daruwala, P., et al.[2019]

Rezafungin, a new echinocandin for treating fungal infections, was found to be safe and well-tolerated in a study of healthy adults, with no serious adverse events reported after a single subcutaneous dose.

The pharmacokinetic profile of rezafungin showed a long half-life of 193 hours and significant exposure, suggesting it could be effective for prolonged treatment, although injection site reactions were a concern that may require formulation adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I randomized, double-blind, single subcutaneous dose escalation study to determine the safety, tolerability, and pharmacokinetics of rezafungin in healthy adult subjects. Gu, K., Ruff, D., Key, C., et al.[2022]

Rezafungin shows broad in vitro activity against various Candida species, including C. auris, and has similar species-specific effectiveness compared to other echinocandins like anidulafungin and micafungin.

However, rezafungin was found to be less active overall than anidulafungin and micafungin on a milligram-per-liter basis, and a notable proportion of C. auris isolates exhibited mutations that conferred cross-resistance to echinocandins, indicating potential challenges in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rezafungin In Vitro Activity against Contemporary Nordic Clinical Candida Isolates and Candida auris Determined by the EUCAST Reference Method. Helleberg, M., Jørgensen, KM., Hare, RK., et al.[2021]

Rezafungin, a long-acting echinocandin, has shown broad-spectrum effectiveness against various Candida and Aspergillus species, including some drug-resistant strains, and is currently in phase III trials.

In a compassionate use case, rezafungin was successfully used for over a year to treat a patient with a multidrug-resistant Candida glabrata infection, indicating its potential safety and efficacy in challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded Access Use of Rezafungin for Salvage Therapy of Invasive Candida glabrata Infection: A Case Report. Adeel, A., Qu, MD., Siddiqui, E., et al.[2023]

Rezafungin demonstrated non-inferior efficacy compared to caspofungin in treating candidaemia and invasive candidiasis, with similar rates of global cure at day 14 and 30-day all-cause mortality in a phase 3 trial involving 199 patients.

The safety profile of rezafungin was comparable to caspofungin, with no concerning trends in treatment-emergent or serious adverse events, indicating it is a viable option for patients with invasive fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial. Thompson, GR., Soriano, A., Cornely, OA., et al.[2023]

Rezafungin acetate is a promising new antifungal treatment that can be administered once a week due to its long half-life, making it convenient for patients.

In studies using neutropenic mouse models, rezafungin showed effective treatment against serious fungal infections, including those caused by azole-resistant Candida albicans and aspergillosis, highlighting its potential for treating invasive fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rezafungin treatment in mouse models of invasive candidiasis and aspergillosis: Insights on the PK/PD pharmacometrics of rezafungin efficacy. Miesel, L., Lin, KY., Ong, V.[2023]

Rezafungin demonstrated strong in vitro activity against both common and rare Candida species, with MIC90 values indicating effectiveness at very low concentrations (0.06-2 mg/L) across various species.

It was particularly effective against azole-resistant strains of Candida, showing similar efficacy to other echinocandins, except for caspofungin, suggesting it could be a valuable treatment option for resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro activity of rezafungin against common and rare Candida species and Saccharomyces cerevisiae. Tóth, Z., Forgács, L., Locke, JB., et al.[2020]

Rezafungin, an intravenous echinocandin, has been approved in the USA for treating candidaemia and invasive candidiasis in adults who have limited treatment options, highlighting its efficacy in addressing serious fungal infections.

In addition to its approved use, rezafungin is being developed for preventing invasive fungal diseases in patients undergoing blood and marrow transplants, indicating its potential broader application in immunocompromised populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rezafungin: First Approval. Syed, YY.[2023]

Rezafungin is a new long-acting echinocandin that shows improved tissue penetration and pharmacokinetics compared to older echinocandins, allowing for potential once-weekly intravenous administration and better flexibility in dosing and storage.

It has a good safety profile with no evidence of toxic effects at higher doses, which may help prevent the development of resistant fungal strains, while maintaining similar efficacy and resistance patterns to existing echinocandins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rezafungin-Mechanisms of Action, Susceptibility and Resistance: Similarities and Differences with the Other Echinocandins. Garcia-Effron, G.[2020]

Rezafungin (CD101) demonstrated effective in vitro activity against various Candida species, with the lowest minimum inhibitory concentrations (MICs) observed for C. albicans, indicating its potential as a treatment for invasive candidiasis.

Significant interlaboratory variation was noted in the susceptibility results for C. albicans, suggesting the need for further investigation to standardize testing methods and ensure consistent results across different laboratories.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicentre determination of rezafungin (CD101) susceptibility of Candida species by the EUCAST method. Arendrup, MC., Meletiadis, J., Zaragoza, O., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11920862/

Long-term Safety and Effectiveness of Rezafungin Treatment ... In the phase 2 STRIVE trial, overall cure rates were 76.1% with once-weekly IV rezafungin (week 1: 400 mg; week 2 onwards: 200 mg) and 67.2% ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04368559

NCT04368559 | Study of Rezafungin Compared to ... The purpose of this pivotal study is to determine if intravenous Rezafungin is efficacious and safe in the prevention of invasive fungal diseases

3. cidara.com cidara.com/news/cidara-therapeutics-highlights-new-data-from-multiple-rezafungin-studies-presented-at-eccmid-2019/

Cidara Therapeutics Highlights New Data from Multiple ... Data featured in three oral and five poster presentations reinforce potential of novel antifungal for the treatment and prevention

4. thelancet.com thelancet.com/article/S1473-3099(23)00551-0/fulltext

Efficacy and safety of rezafungin and caspofungin in ... Mycological eradication rates and negative blood culture results suggest that rezafungin treatment could achieve rapid infection clearance.

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/217417Orig1s000IntegratedR.pdf

217417Orig1s000 - accessdata.fda.gov rezafungin or standard comparator for the prevention of invasive fungal diseases in the allogeneic blood/bone marrow transplant population ...

6. cormedix.com cormedix.com/cormedix-announces-completion-of-enrollment-in-phase-iii-respect-clinical-trial-for-rezzayo/

CORMEDIX ANNOUNCES COMPLETION OF ... REZZAYO is currently approved for the treatment of candidemia and invasive candidiasis in adults, with an ongoing Phase III study for the ...

7. academic.oup.com academic.oup.com/ofid/article/12/9/ofaf555/8253965

Rezafungin Versus Caspofungin for the Treatment of ... At Day 5, mycological eradication rates were 68.7% (79/115) and 63.2% (74/117) with rezafungin and caspofungin, respectively; corresponding ...

8. infectiousdiseaseadvisor.com infectiousdiseaseadvisor.com/news/rezafungin-is-safe-and-efficacious-for-candidemia-invasive-candidiasis/

Rezafungin Is Safe and Efficacious Against Adult ... At 30 days, all-cause mortality occurred among 19.1% and 19.7% of rezafungin and caspofungin recipients, respectively, indicating noninferiority ...