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Safety and efficacy of PC945 in combination with other antifungal therapy for the treatment of refractory invasive pulmonary aspergillosis

Phase 3
Conditions
Health Condition 1: B440- Invasive pulmonary aspergillosis
Registration Number
CTRI/2023/11/059601
Lead Sponsor
PSI CRO Pharma Pvt Ltd
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Yet Recruiting
Sex
Not specified
Target Recruitment
0
Inclusion Criteria

Potential study subjects must satisfy all the following inclusion criteria to be eligible to enter the study:

1. Subject is = 18 years

2. Subject has provided written or electronic informed consent in a manner approved by the applicable Institutional Review Board (IRB) or Research Ethics Committee (REC), which includes permission to retrieve pre-specified data from their historic medical records.

3. Subject is able to perform and willing to comply with the study visits, laboratory assessments, and other study-related procedures

4. Female of child-bearing potential must be non-lactating and must have a negative pregnancy test at screening

5. Female subject of childbearing potential and male subject with female partner of childbearing potential must agree to either remain abstinent or use adequate and reliable contraception throughout the study and until 30 days after the last dose of study medication or of SOC mold-active treatment (Refer to Section 9.2 for acceptable forms of contraception)

6. Subject has proven or probable IPA according to the 2019 EORTC/MSGERC consensus definitions (see Table 5 and Table 6, Appendix 16.6.1). If the subject is a lung transplant recipient and the diagnosis of proven or probable IPA is not confirmed using the 2019 EORTC/MSGERC criteria, the diagnosis of proven or probable IPA can be confirmed using the 2010 ISHLT consensus statements for the definitions of infections in cardiothoracic transplant recipients (see Table 7, Table 8 and Table 9, Appendix 16.6.2)

7. Subject’s IPA has an unfavorable response to adequate antifungal therapy defined as follows:

a. Progression of disease after receiving at least seven days of adequate antifungal therapy for the treatment of IPA (see Table 11 in Appendix 16.6.4 for the definitions of adequate antifungal therapy).

In subjects with parenchymal disease progression of IPA is defined as:

8. worsening or new clinical symptoms or signs AND

9. worsening or new radiological features attributed to IPA AND

10. mycological evidence of persistent infection.

In patients with tracheobronchial or anastomotic disease, progression of IPA is defined as:

11. worsening or new clinical symptoms or signs OR

12. worsening or new abnormalities attributable to IPA visualized on bronchoscopy OR

13. worsening or new radiological features attributed to IPA AND

14. mycological evidence of persistent infection.

In either situation, mycological evidence of persistence can include any one of the following:

15. positive sputum or BAL sample culture for Aspergillus spp;

16. histological presence of invasive hyphae consistent with Aspergillus spp. in infected tracheobronchial or pulmonary sites;

17. GM ODI > 0.5 in blood or BAL fluid (using the Bio-Rad Platelia Aspergillus enzyme immunoassay or the IMMY s ?na Aspergillus Galactomannan Lateral Flow Assay with an automated cube reader);

18. Aspergillus PCR positive in blood, BAL fluid or sputum

OR:

b.Stability of disease after at least fourteen days of adequate antifungal therapy for the treatment of IPA (see Table 11 in Appendix 16.6.3 for the definitions of adequate antifungal therapy).

In subjects with parenchymal disease stability of IPA is defined as:

19. minor or no improvement in attributable clinical symptoms or signs AND

20. stabilizati

Exclusion Criteria

Potential study subjects must satisfy none of the Exclusion Criteria to be eligible to enter the study.

1.Subject with possible IPA

2.Subject with non-invasive pulmonary aspergillosis including simple tracheobronchitis, chronic pulmonary aspergillosis, aspergilloma or Allergic bronchopulmonary aspergillosis (ABPA)

3. Subject with extra-pulmonary aspergillus disease (with the exception of those with sinopulmonary aspergillosis only) or disseminated invasive aspergillosis with clinical or radiological manifestations in other organs

4. Subject has pulmonary Aspergillus disease infected with Aspergillus spp. known to be resistant to posaconazole, or to itraconazole, or to voriconazole

5. Subject has pulmonary fungal disease due to, or fungal co-infection with, a non-Aspergillus mold

6. Subject has a medical history of Coccidioidomycosis or positive Coccidioides immitis Immunoglobulin G at or before screening

7. Subject has medical history of Cryptococcosis or of Histoplasmosis requiring antifungal suppressive or prophylactic treatment

8.Subject has had a positive culture for Mycobacterium abscessus within 6 months before screening or is currently receiving treatment for Mycobacterium abscessus

9.Subject has an endobronchial stent in situ

10.Subject is in the ICU

11.Subject is diagnosed with the immune reconstitution inflammatory syndrome at screening, in the clinical judgment of the investigator

12.Subject has aplastic anemia

13.Subject with a Karnofsky score < 20

14.Subject is receiving palliative care or whose life expectancy is not expected to be sustained for the duration of the trial in the opinion of the investigator

15.Subject with a known or suspected 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

16.Subject who has previously received PC945

17.Subject with a known history of allergy, hypersensitivity, or any previous serious reaction to any component of the PC945 or placebo formulations

18.Subject who is due to receive at any time during the study, an investigational medicinal agent

19.Subject who is participating, or who is due to participate at any time during the study, in a therapeutic or diagnostic clinical trial

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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