Senolytics Treatment of Interstitial Lung Disease in Common Variable Immunodeficiency

Study Overview
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Brief Summary
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The purpose of this study is to determine if the supplement, Fisetin, can be used as a treatment option for common variable immunodeficiency (CVID) by comparing its efficacy to placebo.

Official Title
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Senolytics as a Novel Treatment for Interstitial Lung Disease in Common Variable Immunodeficiency (CVID)

Conditions
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Common Variable Immunodeficiency, Interstitial Lung Disease Due to Systemic Disease

Intervention / Treatment
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* Drug: Fisetin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must have received a diagnosis of CVID according to the international consensus document (ICON) at least 30 days before enrollment. Physician diagnosis of possible GLILD associated with CVID. IgA results. Female patient is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile. (A negative pregnancy test for women whose menopausal status is determined by self-reported absence of menstrual periods in the past 12 months will be required within 72 hours prior to randomization). Patient must be able and willing to comply with the requirements of this study protocol. Exclusion Criteria: Unable or unwilling to give informed consent. Presence of any condition that the Investigator or the subject's attending physician believes would put the subject at risk or would preclude the patient from successfully completing the trial. Pregnant and/or lactating. Women of childbearing potential (WCBP) must have a negative pregnancy test within 72 hours prior to randomization. WCBP who are unwilling to abstain from sex or use an adequate method of contraception from the time of the first IP administration through 48 hours after the last IP administration. Men who are unwilling to abstain from sex with WCBP or use an adequate method of contraception from the time of the first IP administration through 48 hours after the last IP administration. Prisoners, institutionalized individuals, or others who may be considered vulnerable populations, such as individuals with dementia. Patient currently hospitalized or under immediate consideration for hospitalization. Current use of tobacco products or as per clinical judgement. Current excessive caffeine intake (400 mg or more per day).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fisetin Group<br>Subjects will receive the supplement, Fisetin, for 2 cycles of 2 consecutive days (first on days 0 & 1 and then repeated on days 28 & 29) | Drug: Fisetin<br>* 20 mg per kilogram (kg) of body weight supplied in 100 mg capsules and administered orally on days 0, 1, 28, and 29<br>|
| Placebo Comparator: Placebo Group<br>Subjects will receive placebo for 2 cycles of 2 consecutive days (first on days 0 & 1 and then repeated on days 28 & 29) | Drug: Placebo<br>* Looks exactly like the study drug, but it contains no active ingredient. Administered orally on days 0, 1, 28 and 29<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in immunophenotyping of peripheral T lymphocytes | Measured by percentage of activated CD4+25+ T cells | Baseline, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Forced Vital Capacity (FVC) | Measured by spirometry to determine the maximal amount of air that can be forcibly exhaled from the lungs after a full inhale, reported as liters (L) | Baseline, 6 months | 
| Change in radiologic imaging in subjects | Number of subjects to have a 10% improvement with the CT scoring system. Radiologist will score the CT scans at each time point and changes in score at each time point will be noted. | Baseline, 3 months, 6 months | 
| Use of MRI imaging for assessment of GLILD | Number of MRI images that were used to assess for GLILD compared to High-resolution Computed Tomography (HRCT) use | 6 months | 
| Infectious complications | Number of subjects to experience infectious complications | 6 months | 
| Adverse Events | Number of adverse events reported | 6 months | 
| Change in quality of life | Measured using the RAND 36-Short Form Survey Instrument (SF-36). The SF-36 Health Survey is a 36-item, participant-reported survey that measures patient health and disability. Possible scores range from 0 to 100, with 0 indicating maximum disability, and 100 indicating no disability | Baseline, 6 months | 
| Change in 6 minute walk test | Number of subjects to have a 10% improvement in 6 minute walk test. The 6 minute walk test measures the distance a person is able to walk in 6 minutes. | Baseline, 6 months |