Pulmonary Aspergillosis
Conditions
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.
Interventions
DRUGOpelconazole
Nebulizer suspension
DRUGStandard of Care
Standard of Care
Sponsors
Pulmocide Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
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.
Intervention model description
Open-label, randomized, active-controlled, parallel-group multi-center study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Completed 12 Weeks of Therapy | Week 12 | Percentage of Participants Who Completed 12 Weeks of PC945 or Initial Standard of Care (SoC) |
Countries
Canada, United States
Contacts
STUDY_DIRECTORVice President Clinical Development
Pulmocide Ltd
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized 18 to <65 years | 57 Participants |
| Age, Customized 65 to <75 years | 41 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 80 Participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 69 | 2 / 33 |
| other Total, other adverse events | 59 / 65 | 27 / 33 |
| serious Total, serious adverse events | 27 / 65 | 12 / 33 |
Outcome results
None listed