Clinical trial NCT05037851: A Safety Study of PC945 (Opelconazole) Prophylaxis or Pre-emptive Therapy Against Pulmonary Aspergillosis in Lung Transplant Recipients (OPERA-S Study)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Aspergillosis
Lead sponsor: Pulmocide Ltd
Sponsor class: INDUSTRY
First posted: 2021-09-08
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, randomized, active-controlled, parallel-group multi-center study
Primary purpose: PREVENTION

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.

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.

Eligibility 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.

Primary outcomes:
measure: Number of participants who complete 12 weeks of therapy
timeFrame: Baseline to 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Clinical Research Site
state: Arizona
city: La Jolla
country: United States
facility: Clinical Research Site
state: California
city: Los Angeles
country: United States
facility: Clinical Research Site
state: California
city: Jacksonville
country: United States
facility: Clinical Research Site
state: Florida
city: Tampa
country: United States
facility: Clinical Research Site
state: Florida
city: Maywood
country: United States
facility: Clinical Research Site
state: Illinois
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Bronx
country: United States
facility: Clinical Research Site
state: New York
city: New York
country: United States
facility: Clinical Research Site
state: New York
city: Philadelphia
country: United States
facility: Clinical Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Clinical Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Clinical Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Clinical Research Site
state: Tennessee
city: Dallas
country: United States
facility: Clinical Research Site
state: Texas
city: Houston
country: United States
facility: Clinical Research Site 1
state: Texas
city: Houston
country: United States
facility: Clinical Research Site 2
state: Texas
city: Houston
country: United States
facility: Clinical Research Site 3
state: Texas
city: Edmonton
country: Canada
facility: Clinical Research Site
city: Toronto
country: Canada
facility: Clinical Research Site
Study officials:
affiliation: Pulmocide Ltd
name: Vice President Clinical Development
role: STUDY_DIRECTOR
References: