LAmB and Posaconazole for Histoplasmosis

Not yet recruiting at 1 trial location

Overseen By Nathan Bahr, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Minnesota

Must be taking: Antiretrovirals

Must not be taking: Rifampin

Disqualifiers: Pregnancy, Renal impairment, CNS involvement, 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: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for moderate to severe histoplasmosis, a fungal infection, particularly in individuals with HIV. Researchers aim to determine if a single high dose of the existing drug LAmB (liposomal amphotericin B) is more effective than the usual smaller daily doses. They are also evaluating whether a new pill, posaconazole, is safer and more effective than the standard pill, itraconazole, and if a shorter 6-month treatment is as effective as the usual year-long treatment. Ideal candidates for this trial are those hospitalized with suspected or confirmed histoplasmosis who do not have kidney problems or certain other health issues. 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 does not specify if you need to stop taking your current medications, but it mentions that significant drug interactions with itraconazole or posaconazole could exclude you from participating. It's best to discuss your current medications with the trial team.

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

Research has shown that a single high dose of liposomal amphotericin B (LAmB) is generally safe, causing fewer severe side effects than similar treatments, particularly for people with HIV and fungal infections. Studies also suggest that posaconazole is well-tolerated. Patients with fungal infections demonstrated improvement within a month of starting various dosing schedules. These findings indicate that both LAmB and posaconazole have a good safety record in previous studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for histoplasmosis because they offer potentially more effective and convenient options compared to the standard of care. The experimental arm uses a single high-dose of liposomal amphotericin B (LAmB) for induction therapy, which could potentially reduce treatment duration and improve patient compliance compared to the traditional daily dosing. Additionally, posaconazole is used in the experimental consolidation therapy, which may offer improved efficacy and a better side-effect profile compared to the standard itraconazole. These innovations could lead to more effective and patient-friendly treatments for those suffering from histoplasmosis.

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

Research has shown that high-dose liposomal amphotericin B (LAmB), which participants in this trial may receive as part of the induction therapy, effectively treats fungal infections like histoplasmosis, especially in people with HIV. Studies indicate that this treatment causes fewer kidney problems than other types of amphotericin B. Early findings suggest it is safe and reduces the risk of severe side effects compared to traditional doses.

Posaconazole, tested as an experimental consolidation therapy in this trial, has also shown promise in treating histoplasmosis. Patients have experienced significant improvement within the first month of treatment. In some cases, posaconazole has worked well as a backup option when other treatments didn't help. Overall, both LAmB and posaconazole have demonstrated good results in managing histoplasmosis. ^{1 2 3 4 6}

Who Is on the Research Team?

Nathan Bahr, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for adults over 18 hospitalized with suspected or confirmed histoplasmosis, a fungal infection. Participants must have tested positive for the disease and agreed to provide informed consent. It's not specified who cannot join.

Inclusion Criteria

I have given my consent or my surrogate has for me.

I have been diagnosed with histoplasmosis.

I am 18 years old or older.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive either a single high-dose intravenous LAmB (10mg/kg) or SOC daily dosing (3mg/kg) for induction therapy

10 weeks

Weekly visits for monitoring

Consolidation Therapy

Participants receive oral posaconazole or SOC oral itraconazole for consolidation therapy

6-12 months

Monthly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Itraconazole
• LAmB B
• Posaconazole

Trial Overview

The study tests high-dose intravenous LAmB against standard-of-care dosing for initial treatment, oral posaconazole versus itraconazole tablets for follow-up therapy, and compares 6 vs. 12 months of consolidation therapy in HIV-positive patients.

How Is the Trial Designed?

Group I: Total Consolidation - Experimental Experimental Treatment 2 Interventions

6 months total (e.g., 0 additional months) of itraconazole or posaconazole based on assignment from Aim 2.

Group II: Induction Therapy - Experimental Experimental Treatment 1 Intervention

Single high-dose (10mgkg) of LAmB B

Group III: Consolidation Therapy - Experimental Experimental Treatment 1 Intervention

posaconazole

Group IV: Induction Therapy - Standard of Care Active Control 1 Intervention

SOC daily standard dose (3mg/kg) LAmB

Group V: Consolidation Therapy - Standard of Care Active Control 1 Intervention

SOC itraconazole

Group VI: Total Consolidation - Standard of Care Active Control 2 Interventions

12 months total (e.g., 6 additional months) of itraconazole or posaconazole based on assignment from Aim 2

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Federal University of Health Science of Porto Alegre

Collaborator

Trials

125

Recruited

8,700+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10551850/

Safety of Single High-Dose Liposomal Amphotericin B for ...

Evidence for efficacy of single, high-dose liposomal amphotericin B (LAmB) in HIV-associated cryptococcal meningitis and histoplasmosis is growing.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04059770

Study Details | NCT04059770 | Randomized Trial of ...

Liposomal amphotericin B (L-AmB) is considered the therapy of choice for AIDS-associated histoplasmosis.However, many patients in Latin America are still ...

3.

cochranelibrary.com

cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013594/full

Treating progressive disseminated histoplasmosis in ...

Liposomal amphotericin B results in less kidney damage compared to deoxycholate amphotericin B when starting treatment.

4.

infectiousdiseaseadvisor.com

infectiousdiseaseadvisor.com/news/high-dose-liposomal-amphotericin-b-induction-therapy-safe-for-hiv-fungal-infections/

Single High-Dose Liposomal Amphotericin B Safe for HIV ...

The risk for severe AEs in HIV-associated fungal infections was significantly lower with the use of single high-dose LAmB vs traditional ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4856207/

Liposomal Amphotericin B (AmBisome®): A review of the ...

Collectively, these data demonstrate the potential efficacy of LAmB for preventing invasive infections caused by yeasts and molds, however the minimum ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37808894/

Safety of Single High-Dose Liposomal Amphotericin B for ...

Conclusions: Single, high-dose LAmB is associated with a lower risk of life-threatening AEs compared with other World Health Organization- ...