PC945 Prophylaxis or Pre-emptive Therapy Against Pulmonary Aspergillosis in Lung Transplant Recipients

• ClinicalTrials.gov Identifier: NCT05037851
• Recruitment Status: Active, not recruiting
• First Posted: September 8, 2021
• Last Update Posted: July 27, 2023
• Sponsor: Pulmocide Ltd
• Information provided by (Responsible Party): Pulmocide Ltd

Study Description

Brief Summary:

A study to evaluate the safety and tolerability of PC945 for the prevention of fungal aspergillus infections in the lung in patients who have received a lung transplant.

Condition or disease	Intervention/treatment	Phase
Pulmonary Aspergillosis	Drug: PC945; Drug: Standard of Care	Phase 2

Detailed Description:

Part 1 of the study comprises a 12 week Prophylaxis or Pre-emptive Therapy Phase. Part 2 comprises a 4-week Safety Follow-Up Phase.

The study will screen single or double lung transplant recipients due to receive a mold-active antifungal: either as de novo prophylaxis or as pre-emptive therapy (for subjects with Aspergillus spp. colonization of the respiratory tract but no evidence of pulmonary fungal disease). Only subjects who fulfill all the inclusion and none of the exclusion criteria will be randomized.

The presence of post-randomization pulmonary fungal disease or colonization will be adjudicated in all subjects in a blinded fashion by an independent Data Review Committee (DRC) using the 2010 International Society for Heart and Lung Transplant criteria [Husain S et al., 2011]. Pulmonary fungal disease will be categorized by the DRC as bronchial anastomotic infection, tracheobronchitis, fungal pneumonia, or colonization, and will be further categorized as proven or probable.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Open-label, randomized, active-controlled, parallel-group multi-center study
• Masking: Single (Outcomes Assessor)
• Masking Description: The study will be an open-label study. For the purposes of the exploratory efficacy assessments, however, the Data Review Committee determining the presence of pulmonary fungal disease will be blinded as to treatment assignment. The Sponsor will limit knowledge of treatment assignment to as few sponsor personnel as possible to reduce bias.
• Primary Purpose: Prevention
• Official Title: A Randomized Controlled Open-label Study to Assess the Safety and Tolerability of Nebulized PC945 for Prophylaxis or Pre-emptive Therapy Against Pulmonary Aspergillosis in Lung Transplant Recipients
• Actual Study Start Date: November 19, 2021
• Estimated Primary Completion Date: November 2023
• Estimated Study Completion Date: November 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: PC945; 14.8 mg PC945 administered twice daily for 12 weeks	Drug: PC945; Nebulizer suspension; Other Name: Opelconazole
Active Comparator: Standard of Care (SoC); Mold-active SoC prophylaxis/pre-emptive therapy	Drug: Standard of Care; Standard of Care

Outcome Measures

Primary Outcome Measures :

1. Proportion of subjects who complete 12 weeks of therapy [ Time Frame: Baseline to 12 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subject is ≥18 years
2. Subject has received either a single or double lung transplant but did not receive any other organ transplant (e.g., heart, kidney, etc.) at the time of the lung transplantation. History of prior transplant (>1 year) is acceptable
3. Subject or Legally Authorized Representative has provided written or electronic informed consent in a manner approved by the applicable Institutional Review Board (IRB) or Ethics Committee
4. Subject is able to perform and willing to comply with the study visits, laboratory assessments, and other study-related procedures
5. Females of child-bearing potential must be non-lactating, must have a negative pregnancy test at screening, and must agree to be abstinent or to use contraception until 30 days after the last dose of PC945 or of SoC anti-mold prophylaxis or pre-emptive therapy

6a. Cohort 1 (de novo prophylaxis immediately post transplant): subject must be ready to be randomized and start anti-mold prophylaxis within 72 hours of returning to the intensive care unit (ICU) after the transplant surgery or

6b. In Cohort 2 (pre-emptive therapy): subject must meet all of the following:

• Aspergillus spp. colonization of the respiratory tract confirmed within 91 days (13 weeks) after a lung transplant. Colonization is defined according to the 2010 ISHLT Consensus Statement definition criteria for colonization
• Without evidence of pulmonary fungal disease
• Must be ready to start anti-mold medication within 96 hours after the positive culture(s), galactomannan or PCR result(s) were reported

Exclusion Criteria:

1. Subject who would normally receive nebulized amphotericin B as the only mold active antifungal agent as initial SoC prophylaxis or pre-emptive therapy
2. Subject with a fungal disease requiring systemic antifungal treatment at the time of transplant
3. Subject has received a mold active antifungal agent post transplant (Note: a subject who receives a mold active antifungal agent within 24 hours before, during, or after the transplant procedure will not be excluded if the mold active medication was stopped within 72 hours of returning to the ICU after the transplant surgery, or prior to randomization (whichever happens first)
4. Subject who has previously received PC945
5. Subject who is receiving, or who is due to receive at any time during the study, an investigational medicinal agent
6. Subject who is participating, or who is due to participate at any time during the study, in a therapeutic clinical trial. For any other trials (e.g. observational or using approved medication), consultation with Pulmocide and the medical monitor is required.
7. Subject has an endobronchial stent in situ
8. Subject with a known history of allergy, hypersensitivity, or any previous serious reaction to any component of the PC945 formulation, azoles, echinocandins, or amphotericin B
9. Subject with an elevated alanine transaminase (ALT) or, aspartate transaminase (AST) >5 x the upper limit of normal (ULN)
10. Subject with any known history or current evidence of alcohol or drug abuse that, in the Investigator's opinion, would exclude the subject from participation in the study
11. Subject with a concomitant medical condition or post-surgery complication that, in the opinion of the Investigator, may jeopardize adherence to the protocol requirements or impede the accurate measurement of efficacy or may be an unacceptable additional risk to the subject should he/she participate in the study
12. Subject's life expectancy is not expected to be sustained for the duration of the trial (16 weeks), in the opinion of the investigator
13. In Cohort 2 (pre-emptive therapy), subject colonized with a documented azole-, echinocandin-, or amphotericin B resistant Aspergillus organism or with any non Aspergillus mold

Contacts and Locations

Locations

United States, Arizona

Clinical Research Site

Phoenix, Arizona, United States, 85013

United States, California

Clinical Research Site

Los Angeles, California, United States, 90095

Clinical Research Site

San Diego, California, United States, 92610

United States, Florida

Clinical Research Site

Jacksonville, Florida, United States, 32224

Clinical Research Site

Tampa, Florida, United States, 33606

United States, Illinois

Clinical Research Site

Maywood, Illinois, United States, 60153

United States, Missouri

Research Site

Saint Louis, Missouri, United States, 63110

United States, New York

Clinical Research Site

Bronx, New York, United States, 10467

Clinical Research Site

New York, New York, United States, 10016

United States, Pennsylvania

Clinical Research Site

Philadelphia, Pennsylvania, United States, 19104

Clinical Research Site

Philadelphia, Pennsylvania, United States, 19140

Clinical Research Site

Pittsburgh, Pennsylvania, United States, 15213

United States, Tennessee

Clinical Research Site

Nashville, Tennessee, United States, 37232

United States, Texas

Clinical Research Site

Dallas, Texas, United States, 75246

Clinical Research Site

Houston, Texas, United States, 77030

Research Site

Houston, Texas, United States, 77030

Canada

Clinical Research Site

Edmonton, Canada, T6G 1Z1

Clinical Research SIte

Toronto, Canada, M5G 2N2

Sponsors and Collaborators

Pulmocide Ltd

Investigators

• Study Director: Vice President Clinical Development; Pulmocide Ltd

More Information

• Responsible Party: Pulmocide Ltd
• ClinicalTrials.gov Identifier: NCT05037851
• Other Study ID Numbers: PC_ASP_007
• First Posted: September 8, 2021
• Last Update Posted: July 27, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Aspergillosis; Pulmonary Aspergillosis; Mycoses; Bacterial Infections and Mycoses; Infections; Lung Diseases, Fungal; Lung Diseases; Respiratory Tract Diseases