In short

  1. Antifungal clinical trials are complex due to the low incidence of disease, need for urgent patient screening, diversity of patient care settings, and intensive monitoring requirements. Overcoming these challenges requires a CRO with specialized operational expertise
  2. A leading biopharma company strategically selected PSI for its critical antifungal program, building on a highly successful prior antibiotic partnership, and a shared commitment to delivering innovative anti-infective therapies
  3. PSI assigned a dedicated, high-performing team already trusted by the sponsor, ensuring continued engagement to support recruitment in this slow-enrolling program
  4. To meet rapid evaluation of eligibility requirements, PSI’s CRAs provided 24/7 support, allowing quick patient identification and enrollment within hours of admission
  5. Building on the sponsor’s strong development foundation and prior program learnings, PSI partnered with sites to minimize patient loss to follow-up and preserve statistical power
  6. The program has met all trial milestones to date, reflecting strong sponsor oversight and effective collaboration

Clinical trials in fungal infections: Challenging complexity

To run a clinical trial in patients with fungal infections is not easy:

  • Fungal infections are relatively rare: This makes it challenging to enroll enough patients to achieve statistical power within a normal timeframe
  • Infections occur in patients in a range of settings: Fungal infections often occur in ICUs, cancer centers, and transplant units, making patient identification challenging – especially since comorbidities may make them unsuitable for clinical trials
    • Many antifungals have complex PK/PD profiles, making them unsuitable for critically ill patients [1], so in-trial PK/PD monitoring is essential
  • Diagnosis of fungal infections is difficult: Culture testing, though common, is slow and can delay timely enrollment and endpoint assessment
    • Endpoints can be subjective, and regulatory requirements are often strict
  • Fungal resistance, such as with C. auris, is rising [2]: Choosing comparators, inclusion criteria, and interpreting efficacy requires consideration of mutation and multidrug resistance
  • Clinical trials face logistical constraints: Placebo use is unethical in patients with life-threatening infections, especially where there is an established treatment or expectation of deterioration without treatment, limiting where and how placebo can be used. Additionally, country lab capabilities vary, and trials often overrepresent high-income countries

Treatment guidelines for invasive fungal infections rely on clinical trials [3], but the pipeline is relatively dry, with only four new antifungals approved in the last decade and just nine antifungals in clinical development [4]. Developing new antifungals is crucial, given concerns about the toxicity and resistance of currently available treatments [3].

The challenge

A leading biopharma company had partnered with PSI on its high-impact program of antibiotic trials, including a broad anti-infective portfolio spanning pneumonia, bloodstream infections, abSSSI, and pediatric indications.

Following this notable success, the company asked PSI to support its pivotal antifungal program in candidemia and invasive candidiasis, and invasive mold infections. Read on for some solutions being implemented to ensure on-time enrollment.

The solutions

An experienced and familiar team:

Building on the strong collaborative relationship established with the sponsor during a complex antibiotic program, we assigned the same key infectious disease specialists from that program to the antifungal trial. Both PSI and the sponsor were thrilled to reunite with dedicated, professional colleagues, building on an established partnership based on trust, performance, and shared expertise.

Keeping investigators engaged:

Enrollment in antifungal studies is unpredictable, so maintaining investigators’ interest, motivation, and readiness to act remained crucial for CRAs. Given the rarity of eligible patients, sites typically committed to limited annual enrollment, requiring strong sponsor-site alignment. Site burden was minimized through coordinated sponsor-CRO support, enabling investigators to focus on clinical decision-making and patient care.

Rapid lab work:

In antifungal trials, patients must be shown to have the correct fungal infection and fulfill entry criteria regarding prior or current treatment (such as not being over-treated with empiric treatment, which is difficult to accomplish when patients are severely ill). To ensure optimal patient identification, the sponsor and PSI implemented highly-responsive screening processes. The screening period is short; patients must be deemed eligible within hours, which means an extra burden on the CRAs. They, like the KOLs and PIs, need to be ready to act when patients are identified, including in the middle of the night, and liaise to ensure that the correct lab work is performed in a timely manner. Sites were also selected with this in mind.

Following the patients:

Loss to follow-up is a significant problem in trials for acute diseases, and it was no less of a challenge here. Once a patient was treated, they could be hard to follow, as there was no need for them to return to that particular investigator for that particular illness. The sponsor worked closely with PSI and investigators to maintain engagement throughout the trial, and ensure robust follow-up.

The outcome

The sponsor’s antifungal program has achieved all specified milestones to date, demonstrating strong execution and progression according to strategic development plans.

Invasive fungal infections have high mortality rates, so it is essential for physicians to start the standard-of-care treatment without any delays, even though decision about participation in a clinical trial requires time and input from the patient and family. The team identified highly effective approaches, including to run workshops on consenting process during training phase, as investigators, sponsors and PSI could exchange many efficient ideas that could be implemented by the sites to decrease burden and ensure smooth and effective informed consent discussion. It was evident that any tools that facilitating a rapid screening period are much awaited and appreciated by the sites, and we were happy to develop and implement these.

Anna Strokova, Director, Infectious Disease Project Management, PSI

Key takeaways

Strategic partnerships with specialized CROs create a competitive advantage for sponsors. With the right expertise, such partnerships enable the continuity of knowledge and experience, foster positive and productive working relationships, and create efficiencies in knowledge processes and infrastructure – all of which are critical to clinical trial success.

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Abbreviations

abSSSI, acute bacterial skin and skin structure infections;
CRA, Clinical Research Associate;
CRO, Contract Research Organization;
ICU, Intensive Care Unit;
KOL, Key Opinion Leader;
PI, Principal Investigator;
PK/PD, pharmacokinetics/pharmacodynamics.

References

1. Lewis, R., et al., Triazole antifungal drug interactions-practical considerations for excellent prescribing. J Antimicrob Chemother, 2024. 79(6): p. 1203–1217.
2. Mishra, S.K., M. Yasir, and M. Willcox, Candida auris: an emerging antimicrobial-resistant organism with the highest level of concern. The Lancet Microbe, 2023. 4(7): p. e482–e483. 
3. Pappas, P.G., Antifungal clinical trials and guidelines: what we know and do not know. Cold Spring Harb Perspect Med, 2014. 4(11): p. a019745. 
4. WHO, Antifungal preclinical and clinical pipeline review. 2025.Â