Posaconazole for Fungal Infection

Recruiting at 19 trial locations

Overseen By Toll Free Number

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Azole antifungals

Disqualifiers: Cystic fibrosis, Cardiac arrhythmia, others

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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 84 days

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called posaconazole, an antifungal drug, to treat serious fungal infections in young children. Researchers aim to understand how the medicine moves through the body when administered in different forms, such as an IV or a liquid. Participants must be under 2 years old, have a serious fungal infection (excluding candidiasis for certain parts of the trial), and already have or will receive a central line, a special type of tube for administering medicine. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that certain medications are prohibited before starting the study. It's best to discuss your current medications with the study team to see if any need to be adjusted.

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

Research has shown that posaconazole has been safely used by many people. The FDA has already approved it to treat certain fungal infections in adults. Earlier studies reported common side effects such as nausea, vomiting, and diarrhea, which were usually mild and temporary.

In one study, 428 patients with serious fungal infections received posaconazole. Long-term safety data from this study indicated that the treatment was generally well-tolerated. However, like other antifungal drugs, posaconazole might increase the risk of other fungal infections.

The safety of posaconazole in children under 18 is not fully known. Since this trial is in Phase 2, researchers are still learning about how the drug works in young children. This phase helps gather more safety information, so participants will be closely monitored. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Posaconazole is unique because it can be taken as an oral suspension after an initial intravenous (IV) phase, which makes it more convenient for patients transitioning from hospital to home care. Unlike many existing antifungal treatments that require prolonged hospitalization for IV administration, Posaconazole offers a seamless switch to an oral form without compromising effectiveness. Additionally, Posaconazole works by inhibiting the synthesis of ergosterol, an essential component of fungal cell membranes, which is effective against a wide range of fungal infections. Researchers are excited about its potential to simplify treatment regimens and reduce hospital stays, offering a more flexible and patient-friendly option for managing fungal infections.

What evidence suggests that posaconazole could be an effective treatment for invasive fungal infection?

Research has shown that posaconazole effectively treats serious fungal infections. In this trial, participants will receive posaconazole in different forms. One study found that 78.6% of people with a specific fungal infection linked to COVID-19 had positive results and survived when treated with posaconazole. Another study found that posaconazole helped prevent these infections and lowered the risk of death compared to other treatments. Additionally, a real-world review found that 56% of patients improved after using posaconazole for more than a week. These findings suggest posaconazole is a promising option for managing serious fungal infections. ^{6 7 8 9 10}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for children under 2 years old with invasive fungal infections. They must have symptoms of an acute IFI episode, weigh at least 500g, and have a central line in place. Kids can't join if they've had posaconazole recently, cystic fibrosis, certain metabolic disorders, active COVID-19, liver dysfunction or known severe reactions to similar antifungals.

Inclusion Criteria

I have a fungal infection that is not candidiasis, and it responds to POS medication.

The participant (or legally acceptable representative) has provided documented informed consent for the study

I have had symptoms of a fungal infection for less than 30 days.

Exclusion Criteria

Has QTc prolongation at screening >500 msec

I have or might have Gilbert's syndrome.

I have a hereditary sugar digestion problem.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive posaconazole IV and/or PFS formulations. In Panel A, a single dose of IV POS is administered. In Panel B, participants receive IV POS for a minimum of 7 days, then transition to PFS for up to 84 days.

Up to 84 days

Daily visits for IV administration initially, then weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Posaconazole

Trial Overview The study tests how the body processes two forms of posaconazole: intravenous (IV) and oral suspension (PFS), in young kids with fungal infections. It aims to understand the appropriate dosing by observing how the drug moves through their bodies.

How Is the Trial Designed?

Group I: Panel B: POS PFS Experimental Treatment 1 Intervention

Following a minimum of 7 days IV dosing, participants as clinically able will be transitioned from POS IV to POS PFS nominal 6 mg/kg body weight based on weight bands administered on Day 8, once daily to a maximum 84 days.

Group II: Panel B: POS IV Experimental Treatment 1 Intervention

Posaconazole 6 mg/kg body weight administered twice daily by IV infusion on Day 1, and then once daily from Day 2 to a maximum 84 days.

Group III: Panel A: POS IV Experimental Treatment 1 Intervention

Posaconazole 6 mg/kg body weight administered in a single dose by IV infusion on Day 1.

Posaconazole is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Noxafil for:

• Invasive Aspergillus infections
• Candidemia
• Oropharyngeal Candidiasis

Approved in United States as Noxafil for:

• Invasive Aspergillus infections
• Candidemia
• Oropharyngeal Candidiasis

Approved in Canada as Noxafil for:

• Invasive Aspergillus infections
• Candidemia
• Oropharyngeal Candidiasis

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a phase III study involving 330 patients, posaconazole (800 mg/day) showed significantly higher success rates in treating invasive fungal infections compared to external controls, particularly in aspergillosis (42% vs 26%).

Posaconazole was generally well tolerated, even in patients receiving treatment for over a year, indicating its safety profile in long-term use for various refractory fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posaconazole. Keating, GM.[2018]

Posaconazole demonstrated potent antifungal activity against a wide range of clinically important fungi, with MIC(50) and MIC(90) values of 0.063 microg/ml and 1 microg/ml, respectively, based on testing of approximately 19,000 strains across 45 laboratories.

It was particularly effective against resistant strains of Candida and Aspergillus spp., showing superior activity compared to other antifungal agents like itraconazole, fluconazole, and amphotericin B, making it a promising option for treating difficult fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. Sabatelli, F., Patel, R., Mann, PA., et al.[2022]

Posaconazole is an effective antifungal agent for preventing invasive fungal infections, particularly in high-risk patients, and has shown efficacy in treating azole-refractory infections, based on randomized trials and clinical reports.

It has a favorable safety profile, with gastrointestinal disturbances being the most common side effects, and is well tolerated even in long-term use, making it a promising option for managing serious fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posaconazole: when and how? The clinician's view. Katragkou, A., Tsikopoulou, F., Roilides, E., et al.[2013]

Posaconazole is a newly approved antifungal medication with a wide range of effectiveness against various yeasts and filamentous fungi, making it a valuable option for treating fungal infections.

While generally well tolerated, there are concerns about its gastrointestinal absorption, which can affect its efficacy in treating serious infections, particularly in immunosuppressed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of posaconazole in the treatment of oropharyngeal candidiasis. Ianas, V., Matthias, KR., Klotz, SA.[2021]

Posaconazole is an effective antifungal agent approved for preventing and treating invasive fungal infections, particularly in patients with weakened immune systems, such as those undergoing stem cell transplants.

The new gastro-resistant tablet formulation of posaconazole offers significant pharmacokinetic advantages over the oral suspension, including improved absorption, less variability between patients, and the convenience of once-daily dosing, making it the preferred choice for optimizing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posaconazole: a review of the gastro-resistant tablet and intravenous solution in invasive fungal infections. McKeage, K.[2018]

Posaconazole is an orally active triazole antifungal that is currently undergoing phase III clinical trials for treating serious opportunistic fungal infections, such as aspergillosis and candidiasis.

In addition to its primary indications, preclinical studies suggest that posaconazole may also be effective against Cryptococcus neoformans, which causes cryptococcosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posaconazole: SCH 56592. [2019]

A study using MRI on adult and juvenile Beagle dogs showed that the intravenous administration of posaconazole (Noxafil) did not affect brain ventricle volume over three months, indicating its safety regarding brain development in older dogs.

The research highlighted significant natural variability in brain ventricle sizes among dogs, which is important for accurately interpreting the effects of treatments like posaconazole and supports its potential use in children over two years of age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging assessment of the ventricular system in the brains of adult and juvenile beagle dogs treated with posaconazole IV Solution. Hines, CD., Song, X., Kuruvilla, S., et al.[2015]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40023451/

Posaconazole effectiveness in rare invasive fungal infections Positive clinical outcome was 78.6% and overall survival was 78.6% in 323 coronavirus disease-associated mucormycosis infection cases. Conclusions: Despite the ...

2. nature.com nature.com/articles/s41598-024-79512-x

The effectiveness and safety of posaconazole enteric ... This study compared the effectiveness and safety between posaconazole enteric-coated tablet and oral suspension, and provided a real world ...

3. journals.asm.org journals.asm.org/doi/10.1128/aac.00893-18

Clinical Outcomes of Oral Suspension versus Delayed ... A randomized controlled trial concluded that posaconazole more effectively prevented IFIs and was associated with lower all-cause mortality than ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8322488/

Real-world assessment of the effectiveness of posaconazole ... The overall effective remission rate was estimated to be 56.0% in patients who received continuous posaconazole treatment for >7 days, and ...

5. academic.oup.com academic.oup.com/ofid/article/7/Supplement_1/S607/6057623

1161. Effectiveness of Posaconazole in the Treatment of Rare ... Positive clinical outcomes with posaconazole therapy were observed in most patients with CBM (73.9%, 17/23), mycetoma (100%, 2/2), hyalo/phaeo ( ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2015/022003s018s020,0205053s002s004,0205596s001s003lbl.pdf

Noxafil (posaconazole) Label - accessdata.fda.gov Table 9 presents treatment-emergent adverse reactions observed at an incidence of at least 10% in the. OPC/rOPC studies. Prophylaxis of Aspergillus and Candida: ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/posaconazole-oral-route/description/drg-20069121

Posaconazole (oral route) - Side effects & dosage Safety and efficacy have been established. Appropriate studies ... May increase the risk for other fungal infections. Heart disease ...

8. fda.gov fda.gov/files/advisory%20committees/published/NOXAFIL--Safety-and-Drug-Utilization-Review.pdf

Noxafil (posaconazole) Safety and Drug Utilization Review Posaconazole is an azole antifungal initially approved on 15-Sep-2006 as an oral suspension. The oral delayed-release tablets and injection ...

9. ema.europa.eu ema.europa.eu/en/documents/product-information/noxafil-epar-product-information_en.pdf

Noxafil, INN-posaconazole - EMA Paediatric population. The safety and efficacy of posaconazole oral suspension have not been established in children and adolescents aged below 18 years.

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2740948/

Posaconazole (Noxafil), an Extended-Spectrum Oral ... Raad and associates collected the overall long-term safety data of posaconazole in 428 patients with IFIs and 66 patients with FN. ... posaconazole use in the ...