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Interferon-gamma as Adjunctive Therapy in Chronic Pulmonary Aspergillosis: a Randomised Feasibility Study (INCAS)

Primary Purpose

Chronic Pulmonary Aspergillosis, Aspergillosis

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Interferon Gamma-1B 0.1 MG Per 0.5 ML Injection PLUS antifungals as standard of care
Antifungals as standard of care
Sponsored by
Manchester University NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Pulmonary Aspergillosis focused on measuring immunotherapy, interferon gamma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis of CPA Started antifungal treatment for CPA within the last 2 weeks and received no antifungals for CPA in the eight weeks prior Chest CT scan available within the 6 months prior to enrolment Individuals of child bearing potential agree to have pregnancy test an use highly effective contraception Exclusion Criteria: Moderate to severe liver dysfunction (Child-Pugh Class B or C) Renal failure (eGFR <30 mL/min) Clinically diagnosed active depression Active tuberculosis or non-tuberculous mycobacterial (NTM) lung disease Acute infection or other event within the preceding 4 weeks which, as assessed by the investigators, might interfere with the assessment of response to treatment Use of any interferon formulation within the preceding six months Active viral hepatitis infection Pregnancy or breastfeeding Immunosuppression (>15mg prednisolone/day for at least four weeks or equivalent) within the preceding six months Inability to self-administer subcutaneous medications AND lack of a carer who can administer Participants lacking capacity to consent

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    Antifungal

    Antifungal plus inteferon gamma

    Arm Description

    Any oral triazole antifungal as per routine care

    Any oral triazole antifungal as per routine care plus interferon-gamma three times weekly subcutaneously 50 micrograms/m2 for 3 months

    Outcomes

    Primary Outcome Measures

    Proportion of participants retained in the intervention arm
    Proportion of target sample achieved
    Change in maximum cavity wall thickness on CT scan

    Secondary Outcome Measures

    Change in St George's Respiratory Questionnaire (SGRQ) score
    The SGRQ ranges from 0-100 with higher scores indicating worse quality of life
    Number of exacerbations requiring antibiotics or steroids in the six months before and after starting treatment

    Full Information

    First Posted
    November 29, 2022
    Last Updated
    July 26, 2023
    Sponsor
    Manchester University NHS Foundation Trust
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05653193
    Brief Title
    Interferon-gamma as Adjunctive Therapy in Chronic Pulmonary Aspergillosis: a Randomised Feasibility Study
    Acronym
    INCAS
    Official Title
    Interferon-gamma as Adjunctive Therapy in Chronic Pulmonary Aspergillosis: a Randomised Feasibility Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 2023 (Anticipated)
    Primary Completion Date
    March 2025 (Anticipated)
    Study Completion Date
    September 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Manchester University NHS Foundation Trust

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This study explores the role of treatment with interferon-gamma to improve outcomes in chronic pulmonary aspergillosis (CPA). CPA is a progressive infection caused by the fungus Aspergillus affecting patients with chronic lung disease like Chronic Obstructive Lung Disease (COPD) or previously treated tuberculosis (TB). It causes gradual destruction of lung tissue by slowly enlarging cavities, frequent secondary infections and poor quality of life. Because of its indolent nature and nonspecific x-ray findings, it often remains unrecognised for years. Around 3600 people live with CPA in the United Kingdom. Mortality from CPA may be up to 40% in five years. Treatment for CPA relies on antifungals for prolonged periods, but only around 60% of patients improve. It is often long-term or lifelong as the response is slow and some patients experience relapses. In addition, only one class of oral antifungal drugs is licensed for CPA, and they are associated with side effects and high cost. Better treatments are needed for CPA. We do not know why many patients do not respond to treatment. Maybe CPA patients have a weakened immune system and are more susceptible to Aspergillus. Our data suggest that CPA patients produce lower amounts of ΙFNγ, a substance that facilitates the immune system's response against Aspergillus. We have also shown that, when given to patients with CPA who have failed to improve on antifungal treatment, interferon-gamma leads to improvement in important patient-centred outcomes like flares of lung disease or hospital admissions. Interferon-gamma is already in use in the National Health Service of the United Kingdom for other indications. Therefore, its use in CPA should be explored. However, CPA is a rare condition and the tolerability of interferon-gamma is not fully established in these patients. To understand whether a large-scale study is feasible in CPA, we first need preliminary data in smaller numbers of patients. We propose a randomised trial of interferon-gamma in addition to antifungals in CPA. Patients with CPA starting antifungal treatment will be eligible. Participants (25 per group) will be randomly assigned to interferon-gamma for 12 weeks (in addition to antifungals) or antifungals only. To test whether the treatment works, we will use measurements of the cavities on chest CT scan and scores on a quality-of-life questionnaire. We will assess for tolerability of treatment at intervals similar to clinical practice. Criteria for progression to the large-scale study will be set based on the proportion of patients willing to participate, and on the proportion who complete the treatment. Data collected on those parameters will allow us to determine the number needed for a definite study. If the large-scale study confirms our observations that interferon-gamma improves outcomes in CPA, then treatment duration can be shortened and relapses avoided. In addition, interferon-gamma can then be explored in other chronic lung disease.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Pulmonary Aspergillosis, Aspergillosis
    Keywords
    immunotherapy, interferon gamma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    50 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Antifungal
    Arm Type
    Active Comparator
    Arm Description
    Any oral triazole antifungal as per routine care
    Arm Title
    Antifungal plus inteferon gamma
    Arm Type
    Experimental
    Arm Description
    Any oral triazole antifungal as per routine care plus interferon-gamma three times weekly subcutaneously 50 micrograms/m2 for 3 months
    Intervention Type
    Drug
    Intervention Name(s)
    Interferon Gamma-1B 0.1 MG Per 0.5 ML Injection PLUS antifungals as standard of care
    Intervention Description
    Patients starting oral antifungal treatment for chronic pulmonary aspergillosis will be randomised 1:1 to additional interferon-gamma for 3 months or no additional treatment.
    Intervention Type
    Drug
    Intervention Name(s)
    Antifungals as standard of care
    Intervention Description
    Patients starting oral antifungal treatment for chronic pulmonary aspergillosis will be randomised 1:1 to additional interferon-gamma for 3 months or no additional treatment.
    Primary Outcome Measure Information:
    Title
    Proportion of participants retained in the intervention arm
    Time Frame
    6 months
    Title
    Proportion of target sample achieved
    Time Frame
    3 years
    Title
    Change in maximum cavity wall thickness on CT scan
    Time Frame
    6 months
    Secondary Outcome Measure Information:
    Title
    Change in St George's Respiratory Questionnaire (SGRQ) score
    Description
    The SGRQ ranges from 0-100 with higher scores indicating worse quality of life
    Time Frame
    3 and 6 months
    Title
    Number of exacerbations requiring antibiotics or steroids in the six months before and after starting treatment
    Time Frame
    1 year

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Diagnosis of CPA Started antifungal treatment for CPA within the last 2 weeks and received no antifungals for CPA in the eight weeks prior Chest CT scan available within the 6 months prior to enrolment Individuals of child bearing potential agree to have pregnancy test an use highly effective contraception Exclusion Criteria: Moderate to severe liver dysfunction (Child-Pugh Class B or C) Renal failure (eGFR <30 mL/min) Clinically diagnosed active depression Active tuberculosis or non-tuberculous mycobacterial (NTM) lung disease Acute infection or other event within the preceding 4 weeks which, as assessed by the investigators, might interfere with the assessment of response to treatment Use of any interferon formulation within the preceding six months Active viral hepatitis infection Pregnancy or breastfeeding Immunosuppression (>15mg prednisolone/day for at least four weeks or equivalent) within the preceding six months Inability to self-administer subcutaneous medications AND lack of a carer who can administer Participants lacking capacity to consent
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Chris Kosmidis, MD
    Phone
    01612915875
    Email
    chris.kosmidis@manchester.ac.uk
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Chris Kosmidis, MD
    Organizational Affiliation
    Manchester University NHS Foundation Trust
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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