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

Sponsor

Pulmocide Ltd (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05037851

Collaborator

(none)

100

Enrollment

Locations

Arms

7.4

Anticipated Duration (Months)

5.3

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

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

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Open-label, randomized, active-controlled, parallel-group multi-center studyOpen-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 :

Nov 19, 2021

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Jul 1, 2022

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: PC945

14.8 mg PC945 administered twice daily for 12 weeks

Drug: PC945

Nebulizer suspension

Other Names:

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

Proportion of subjects who complete 12 weeks of therapy [Baseline to 12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subject is ≥18 years
Subject has received either a single or double lung transplant
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
Subject is able to perform and willing to comply with the study visits, laboratory assessments, and other study-related procedures
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 48 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 72 hours after the positive culture(s), galactomannan or PCR result(s) were reported

Exclusion Criteria:

Subject who would normally receive nebulized amphotericin B as the only mold active antifungal agent as initial SoC prophylaxis or pre-emptive therapy
Subject with a fungal disease requiring systemic antifungal treatment at the time of transplant
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 48 hours of returning to the ICU after the transplant surgery, or prior to randomization (whichever happens first)
Subject who has previously received PC945
Subject who is receiving, or who is due to receive at any time during the study, an investigational medicinal agent
Subject who is participating, or who is due to participate at any time during the study, in a therapeutic or diagnostic clinical trial
Subject has an endobronchial stent in situ
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
Subject with an elevated alanine transaminase (ALT) or, aspartate transaminase (AST)

5 x the upper limit of normal (ULN)

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
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
Subject's life expectancy is not expected to be sustained for the duration of the trial (16 weeks), in the opinion of the investigator
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

	Site	City	State	Country	Postal Code
1	Clinical Research Site	Phoenix	Arizona	United States	85013
2	Clinical Research Site	San Diego	California	United States	92610
3	Clinical Research Site	Gainesville	Florida	United States	32610
4	Clinical Research Site	Tampa	Florida	United States	33606
5	Clinical Research Site	Chicago	Illinois	United States	60610
6	Clinical Research Site	Maywood	Illinois	United States	60153
7	Research Site	Saint Louis	Missouri	United States	63110
8	Clinical Research Site	Bronx	New York	United States	10467
9	Clinical Research Site	New York	New York	United States	10016
10	Clinical Research Site	Philadelphia	Pennsylvania	United States	19104
11	Clinical Research Site	Philadelphia	Pennsylvania	United States	19140
12	Clinical Research Site	Pittsburgh	Pennsylvania	United States	15213
13	Clinical Research Site	Dallas	Texas	United States	75246
14	Clinical Research Site	Houston	Texas	United States	77030
15	Research Site	Houston	Texas	United States	77030
16	Clinical Research Site	Houston	Texas	United States	77032
17	Clinical Research Site	Falls Church	Virginia	United States	22042
18	Clinical Research Site	Edmonton		Canada	T6G 1Z1
19	Clinical Research SIte	Toronto		Canada	M5G 2N2

Sponsors and Collaborators

Pulmocide Ltd

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Pulmocide Ltd

ClinicalTrials.gov Identifier:

NCT05037851

Other Study ID Numbers:

PC_ASP_007

First Posted:

Sep 8, 2021

Last Update Posted:

Jun 15, 2022

Last Verified:

Aug 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Aspergillosis

Pulmonary Aspergillosis

Study Results

No Results Posted as of Jun 15, 2022