Clinical Trial Results:
A double-blind, placebo-controlled study to assess the effects of inhaled PC945 in the treatment of culture-positive Aspergillus or Candida fungal bronchitis in subjects with moderate to severe asthma or other chronic respiratory diseases.
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Summary
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EudraCT number |
2018-000244-26 |
Trial protocol |
GB |
Global end of trial date |
01 Jun 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Aug 2021
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First version publication date |
07 Aug 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
PC-ASP-004
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03745196 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Pulmocide Ltd
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Sponsor organisation address |
44 Southampton Buildings, London, United Kingdom, WC2A 1AP
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Public contact |
Dr Lance Berman, Pulmocide Ltd, +34 660 745 200 , Lance@pulmocide.com
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Scientific contact |
Dr Lance Berman, Pulmocide Ltd, +34 660 745 200 , Lance@pulmocide.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 May 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Jan 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Jun 2020
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To investigate the antifungal effect of PC945 on A. fumigatus complex/A. niger complex or Candida spp. in sputum.
Due to the early termination of the trial due to the COVID-19 pandemic only 13 patients were randomised. As a result, a robust statistical analysis for the primary endpoint could not be conducted.
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practice and applicable regulatory requirements. Known instances of non-conformance were documented and are not considered to have had an impact on the overall conclusions of the study.
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Background therapy |
In addition to their study treatment subjects were treated according to their standard of care treatment | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Dec 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 13
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Worldwide total number of subjects |
13
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
3
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From 65 to 84 years |
10
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85 years and over |
0
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Recruitment
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Recruitment details |
Forty evaluable subjects were required to complete the study. Thirteen subjects participated in the study between 10 December 2018 and 15 January 2020. Eleven subjects completed the study; two subjects terminated the study early; four subjects ended treatment early but completed study visits. | ||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 38 subjects were screened for the study. Twenty-five subjects failed screening. Thirteen subjects met all of the eligibility criteria and were randomised to receive treatment. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Assessor | ||||||||||||||||||
Blinding implementation details |
Due to a difference in appearance of the active and placebo treatments, the investigational product was prepared and dosed by independent staff team members who did not undertake any other study duties.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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PC945 | ||||||||||||||||||
Arm description |
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Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
PC945
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nebuliser suspension
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Routes of administration |
Inhalation use
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Dosage and administration details |
PC945 5mg (emitted dose) administered once daily for 28 days
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Arm title
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Placebo | ||||||||||||||||||
Arm description |
- | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nebuliser solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
Placebo, once daily inhalation via nebuliser for 28 days
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Baseline characteristics reporting groups
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Reporting group title |
PC945
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
PC945
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
- | ||
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End point title |
Proportion of subjects in the ITT population with A. fumigatus complex/A. niger complex negative or Candida spp. reduced by 50% at Visit 5 [1] | |||||||||
End point description |
Analysis conducted on subjects with a positive Aspergillus value or a Candida spp. CFU count >200 at baseline and with an evaluable sputum sample at Visit 5.
Mean A. fumigatus complex/A. niger complex and Candida spp. CFUs declined similarly in both groups between baseline and the end of the study. However, the small sample size, imbalance at baseline between groups in fungal load, and the high variability of the fungal data throughout the study confounded the analyses.
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End point type |
Primary
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End point timeframe |
Baseline to Visit 5 i.e. 4-7 days post end of 28 days treatment
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to the early termination of the trial due to the COVID-19 outbreak and limited subject numbers on both treatment arms to enable a robust analysis, no statistical analysis was performed on these data. |
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| Notes [2] - low subject numbers confounded analysis [3] - low subject numbers confounded analysis |
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| No statistical analyses for this end point | ||||||||||
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End point title |
PC945 Cmax Day 1 [4] | ||||||||
End point description |
Maximum PC945 plasma concentration observed from time 0 to 2 hours post dose; summary statistics provided.
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End point type |
Secondary
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End point timeframe |
Day 1
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| Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Pharmacokinetic results are reported for those patients on PC945 treatment; not applicable for the placebo arm. |
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| No statistical analyses for this end point | |||||||||
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End point title |
PC945 Cmax Day 14 [5] | ||||||||
End point description |
Maximum PC945 plasma concentration observed from time 0 to 2 hours post dose; summary statistics provided.
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End point type |
Secondary
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End point timeframe |
Day 14
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| Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Pharmacokinetic results are reported for those patients on PC945 treatment; not applicable for the placebo arm. |
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| No statistical analyses for this end point | |||||||||
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End point title |
PC945 AUC 0-2h Day 1 [6] | ||||||||
End point description |
Area under the PC945 plasma concentration - time curve from 0 to 2 hour post dose; summary statistics provided.
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End point type |
Secondary
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End point timeframe |
Day 1
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| Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Pharmacokinetic results are reported for those patients on PC945 treatment; not applicable for the placebo arm. |
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| No statistical analyses for this end point | |||||||||
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End point title |
PC945 AUC 0-2h Day 14 [7] | ||||||||
End point description |
Area under the PC945 plasma concentration-time curve from 0 to 2 hour post dose; summary statistics provided.
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End point type |
Secondary
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End point timeframe |
Day 14
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| Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Pharmacokinetic results are reported for those patients on PC945 treatment; not applicable for the placebo arm. |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All AEs whether serious or non-serious, were reported from Visit 3 (baseline) until completion of the subject's last study-related procedure.
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Adverse event reporting additional description |
PC945 was well tolerated in this study and no systemic or pulmonary safety signals were detected with no evidence of drug-induced bronchospasm or any of the AEs known to be associated with the triazole class of antifungal medications.
Two SAEs were reported and were assessed as unrelated by the Sponsor.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.1
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Reporting groups
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Reporting group title |
PC945
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | ||||||||||
Date |
Amendment |
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17 Jul 2018 |
Amendment 1, included:
New phototoxicity data (removing the need for related study restrictions) and updated First In Human blinded safety data. It also included clarifications to the AE collection period and other minor changes and corrections. |
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11 Dec 2018 |
Amendment 2, included:
Revisions to the eligibility criteria including the addition of subjects on GINA step 5 treatment plans and exclusion of patients with clinically significant bacterial chest infection which is not adequately treated at the screening visit.
Addition of unblinded safety data from the First In Human study.
Clarification on period within which oral antifungal therapy, a prohibited medication, can be used prior to study visit.
Removal of the requirement for patients to fast prior to collection of samples for measurement of blood glucose levels.
Minor changes and corrections were made throughout the document. |
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07 Jun 2019 |
Amendment 3 included:
Revisions to the eligibility criteria including the addition of subjects with other chronic respiratory diseases as well as asthma.
Revisions to the eligibility criteria including the addition of subjects with Candida infection up to a maximum of 10.
Revisions to the eligibility criteria including the addition of subjects with Aspergillus niger infection as well as Aspergillus fumigatus.
Addition of background information about Candida infection and other chronic respiratory lung conditions.
Removal of unblinded safety data from the First In Human study as this data had been added to the IB.
Updates to the study objectives and endpoints to reflect the changes to the study population which included changes to the primary endpoint.
Change to dispensing procedures so that all study medication is dispensed at Day 1.
Update to the statistical section to reflect changes to the endpoints and study population. The sample size calculation had been re-evaluated.
Minor changes and corrections were made throughout the document (to ensure consistency with the new study population and objectives and endpoints). |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | ||||||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | ||||||||||
| Due to the early termination of the study due to the COVID-19 outbreak only a limited number of subjects were enrolled. As a result no formal analyses are presented for the primary endpoint and additional secondary endpoints. | ||||||||||
