A Safety Study of PC945 (Opelconazole) Prophylaxis or Pre-emptive Therapy Against Pulmonary Aspergillosis in Lung Transplant Recipients (OPERA-S Study)

• ClinicalTrials.gov Identifier: NCT05037851
• Recruitment Status: Completed
• First Posted: September 8, 2021
• Last Update Posted: January 12, 2024
• Sponsor: Pulmocide Ltd
• Information provided by (Responsible Party): Pulmocide Ltd

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Pulmonary Aspergillosis	Drug: Opelconazole; 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 participants with Aspergillus spp. colonization of the respiratory tract but no evidence of pulmonary fungal disease). Only participants who fulfill all the inclusion and none of the exclusion criteria will be randomized.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Open-label, randomized, active-controlled, parallel-group multi-center study
• Masking: None (Open Label)
• 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 (OPERA-S Study)
• Actual Study Start Date: November 19, 2021
• Actual Primary Completion Date: October 19, 2023
• Actual Study Completion Date: November 13, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Opelconazole; 14.8 mg opelconazole administered twice daily for 12 weeks	Drug: Opelconazole; Nebulizer suspension; Other Name: PC945
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. Number of participants 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

Key Inclusion Criteria:

2. Participant 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

6a. (De novo prophylaxis immediately post transplant): participant 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. (Pre-emptive therapy): participant 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 International Society for Heart Lung Transplantation (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 polymerase chain reaction (PCR) result(s) were reported

Key Exclusion Criteria:

1. Participant would normally receive nebulized amphotericin B as the only mold active antifungal agent as initial SoC prophylaxis or pre-emptive therapy
2. Fungal disease requiring systemic antifungal treatment at the time of transplant
3. Has received a mold active antifungal agent post-transplant (Note: a participant 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. Has previously received opelconazole
5. Is receiving, or who is due to receive at any time during the study, an investigational medicinal agent
6. 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. Has an endobronchial stent in situ
8. Known history of allergy, hypersensitivity, or any previous serious reaction to any component of the opelconazole formulation, azoles, echinocandins, or amphotericin B
9. Elevated alanine transaminase (ALT) or, aspartate transaminase (AST) > 5 x the upper limit of normal (ULN)
10. Any known history or current evidence of alcohol or drug abuse that, in the Investigator's opinion, would exclude the participant from participation in the study

12. Life expectancy is not expected to be sustained for the duration of the trial (16 weeks), in the opinion of the investigator

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

United States, Arizona

Clinical Research Site

Phoenix, Arizona, United States, 85013

United States, California

Clinical Research Site

La Jolla, California, United States, 92037

Clinical Research Site

Los Angeles, California, United States, 90095

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 1

Houston, Texas, United States, 77030

Clinical Research Site 2

Houston, Texas, United States, 77030

Clinical Research Site 3

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: January 12, 2024
• Last Verified: January 2024

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