Histoplasmosis Induction and Consolidation Therapy Factorial Randomized Clinical Trial (Histo-FACT)

NCT07261150 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: IDIM-2025-33491
• Study Type: interventional
• Target: 664
• Locations: 2 countries
• Sites: 2

Brief Summary

The purpose of the study is threefold:

1. 1.Assess the safety and efficacy of a single high-dose intravenous (LAmB 10mg/kg) compared to the SOC daily dosing (3mg/kg) of the same medication for induction therapy in moderate to severe histoplasmosis.
2. 2.Assess the safety and efficacy of oral posaconazole 300mg delayed-release tablets three times daily for two days then once daily for consolidation therapy compared to SOC oral itraconazole 200 mg capsules three times daily for three days then twice daily in moderate to severe histoplasmosis
3. 3.Assess the safety and efficacy of 6 months of consolidation therapy compared to the SOC 12 months of consolidation therapy in persons with HIV on appropriate antiretroviral therapy.

Conditions

Histoplasmosis

Outcome Measures

Primary Outcomes (3)

• Mortality at 2 weeks

  Week 2

• Mortality at 26 weeks

  Week 26

• SAE-free survival between 26 and 52 weeks from induction therapy among those who survived 26 weeks

  Week 52

Secondary Outcomes (2)

• Aim 1: Hierarchical composite end point

  Week 56

• Aim 2: Hierarchical composite end point

  Week 56

Study Arms (6)

Induction Therapy - Experimental

EXPERIMENTAL

Single high-dose (10mgkg) of LAmB B

Drug: LAmB B

Induction Therapy - Standard of Care

ACTIVE COMPARATOR

SOC daily standard dose (3mg/kg) LAmB

Drug: World Health Organization (WHO)-recommended SOC

Consolidation Therapy - Experimental

EXPERIMENTAL

posaconazole

Drug: Posaconazole

Consolidation Therapy - Standard of Care

ACTIVE COMPARATOR

SOC itraconazole

Drug: WHO-recommended SOC Itraconazole

Total Consolidation - Experimental

EXPERIMENTAL

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

Drug: Posaconazole; Drug: WHO-recommended SOC Itraconazole

Total Consolidation - Standard of Care

ACTIVE COMPARATOR

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

Drug: Posaconazole; Drug: WHO-recommended SOC Itraconazole

Interventions

Posaconazole DRUG

Posaconazole delayed-release tabs, 300mg twice daily on day 1 then once daily

Consolidation Therapy - Experimental; Total Consolidation - Experimental; Total Consolidation - Standard of Care

WHO-recommended SOC Itraconazole DRUG

200mg capsules three times daily x 3 days then twice daily

Consolidation Therapy - Standard of Care; Total Consolidation - Experimental; Total Consolidation - Standard of Care

LAmB B DRUG

intravenous liposomal amphotericin B (10mg/kg)

Induction Therapy - Experimental

World Health Organization (WHO)-recommended SOC DRUG

daily intravenous liposomal amphotericin B 3mg/kg, for 2 weeks or at least 7 days if felt stable for discharge per the clinician

Induction Therapy - Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Hospitalized with suspected histoplasmosis b
• Diagnosis of confirmed or probable histoplasmosis (via positive Histoplasma antigen test, culture, histopathology or microscopy)
• Provision of Informed Consent by participant or surrogate c

You may not qualify if:

• Previous diagnosis of histoplasmosis
• Pregnant persons (all persons who could potentially be pregnant will have a pregnancy test prior to enrollment, and if negative, must agree to contraception for the duration of the study)
• Breastfeeding and unable to stop for the duration of the study
• Renal impairment (serum creatinine or blood urea nitrogen (BUN) \>2.0x upper limit of normal)
• Allergy or contraindication to a study medicine
• More than one dose of an amphotericin product in the prior 7 days
• Suspected central nervous system involvement of histoplasmosis
• Likely to die in the next 48 hours in the judgment of the investigator
• Unlikely to follow up for the duration of the study in the judgement of the investigator
• Significant drug-drug interaction with itraconazole or posaconazole (such as rifampin in persons with TB)
• Current diagnosis of cryptococcosis or leishmaniasis
• QTc interval consistently \>450 milliseconds
• Prisoners
• Unable to take oral medications

Sponsors & Collaborators

• University of Minnesota: lead
• Federal University of Health Science of Porto Alegre: collaborator

Study Sites (2)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Universidade Federal de Ciências da Saúde de Porto Alegre

Porto Alegre, Brazil

Location

MeSH Terms

Conditions

Histoplasmosis

Interventions

posaconazole; World Health Organization

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

United Nations; International Agencies; Organizations; Health Care Economics and Organizations

Study Officials

• Nathan Bahr, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nathan Bahr, MD

CONTACT

612-624-9996; bahrx026@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 3, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1); US (1)