Photo-Protection Trial (NB-UVB vs. Placebo) in High-risk Hospitalized COVID-19 Patients

Study Overview
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Brief Summary
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The purpose of this study to evaluate the translational application of the safe and effective treatment of Narrow-Band Ultraviolet light B-band (NB-UVB) to high-risk COVID-19 patients in an effort to improve their immune and hemostatic imbalance to increase survival and improve outcomes.

Detailed Description
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Study Design This is a multi-center, double blind, randomized control trial designed to assess the safety and efficacy of daily NB-UVB light for patients presenting to site hospitals over the age of 50 with a positive COVID-19 panel and at least one comorbidity. This trial provides adjunctive therapy and no in-hospital treatments need to be modified in any way. The sponsor and the centers acknowledge standards of care are actively evolving and this trial is not intended to interfere in any form. Double Blind: Patient and Health care provider will be blinded to the treatment vs. placebo by use of a non-NB-UVB light card. All dosing and times for treatment and placebo will be calculated the same methods. Arm A: Control: Will receive non-NB-UVB light during the Treatment Period. Arm B: Treatment: Will receive NB-UVB light during the Treatment Period. Treatment Phase (Days 1-8): Treatment Schedule will be identical for arm A and B. Follow Up Phase (Days 9-28 or discharge): Follow-up will be identical for arms A and B. Blood Draw Schedule: Blood draws are to be performed after enrollment, before the first treatment day 1 and on days 3, 5, 8, 14 and day of discharge (if prior to day 14 unless blood draw has already occurred within one day of discharge).

Official Title
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Adaptive Photo-Protection Trial: To Demonstrate the Safety and Efficacy of NB-UVB Light Therapy to Improve Outcomes in Hospitalized High-risk Patients With COVID-19

Conditions
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Covid19, Corona Virus Infection, Autoimmune Diseases, Coagulation Disorder, Blood

Intervention / Treatment
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* Device: Narrow Band ultraviolet B-Band Light
* Device: non Narrow Band ultraviolet B-Band Light


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - To be eligible to enroll in the study, subjects must be: In-Hospital 50 years of age or older Hospitalized for COVID-I9 symptoms At least one comorbidity. They have taken a COVID-19 diagnostic test. Peripheral 02 saturation below 94 on room air, nasal cannula or non-rebreather Patients may remain enrolled as long as they remain hospitalized for COVID-19 symptoms and receive a positive test panel for COVID-19 during the treatment phase Be able to provide consent. Exclusion Criteria: - To be eligible to enroll in the study, subjects must not: Require ventilatory support at the time of enrollment. Concurrent pulmonary bacterial infection Taking Light Sensitive Medications Have Lupus Diagnosis Enrolled in an existing Covid-19 Trial Taking In-patient Vitamin oral Supplementation Severe mental or medical disability History of melanoma or dysplastic nevus syndrome Prisoner Active tuberculosis or Cystic Fibrosis, Severe Chronic Obstructive Pulmonary Disease (COPD) or Pulmonary Fibrosis requiring home supplemental oxygen Pre-existing pulmonary hypertension INR > 2, LFT 6 times greater than baseline Stage 3b CKD or ESRD diagnosis before COVID-19 onset Evidence of cirrhosis Evidence of pre-existing vascular disorder or coagulopathy Irreversible bleeding disorder Patients who are not full code Taking oral light sensitizing medications (See Appendix) or using light sensitizing topical medication in the phototherapy treatment zones Taking in patient or at home Vitamin D supplementation Have any photosensitive skin disorder such as Systemic Lupus Erythematosus, Porphyria or Pseudoporphyria, Polymorphous Light Eruption Xeroderma Pigmentosa, Chronic actinic dermatitis, Hydroa vacciniforme, Dermatomyositis Bloom Syndrome, Rothmund Thomas syndrome, Cockayne Syndrome Requiring oxygen supplementation via CPAP/BiPAP, ventilator support, High Flow Nasal Prong therapy (HFNP) Concurrent pulmonary bacterial infection at the time of enrollment Previous hospital admission for COVID-19 symptoms

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 110 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
Interventional Model Description: 1:1 Randomized Placebo Control Trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phototherapy of narrow band ultraviolet Light B-Band NB-UVB<br>Daavlin Series 1 Phototherapy Unit that emits UVB light between 280nm and 320nm. | Device: Narrow Band ultraviolet B-Band Light<br>* Daily doses of NB-UVB for 8 consecutive days.<br>* Other names: Phototherapy;|
| Placebo Comparator: Placebo - Light<br>Daavlin Series 1 Phototherapy Unit that does not emit UVB light between 280nm and 320 nm. | Device: non Narrow Band ultraviolet B-Band Light<br>* Daily doses of non-NB-UVB for 8 consecutive days.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality Rate | % Patient Mortality | 14 days | 
| Mortality Rate | % Patient Mortality | 28 days | 
| WHO Ordinal Scale for Clinical Improvement | Improvement in WHO Ordinal Scale | 14 days | 
| WHO Ordinal Scale for Clinical Improvement | Improvement in WHO Ordinal Scale | 28 days | 
| Length of Hospital Stay | Days from Treatment to Discharge | 28 days | 
| Rate of Escalation to the ICU | % of Patients Escalating to the ICU | day 14 | 
| Rate of Ventilator Support (intubation) requirement | % of Patients Requiring Ventilator Support (intubation) | day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Improved Immune Regulation as measured by (Any 3 of These): | Increased ratio of CD8 perforin to Monocyte IL6, Increased ratio ofNK perforin to Monocyte IL6 Increased ratio of CD4 lFNg to Monocyte IL6 Increased ratio of CD8 perforin to Monocyte TNF Increased ratio ofNK perforin to Monocyte TNF, and Increased ratio of CD4 IFNg to Monocyte TNF | 28 days | 
| Rate of Stabilization of the Immune Dysregulation (all 3 of These) | Decreased Th l and Th 17; Increased Th2; Increased circulating regulatory T Cells | 28 days | 
| Average Reduction in Inflammatory Markers: | HS-CRP (mg/L) | 28 days | 
| Average Reduction in Inflammatory Markers: | LDH (units per liter (U/L)) | 28 days | 
| Average Reduction in Inflammatory Markers: | Ferritin (micrograms/L) | 28 days | 
| Improved Hemostatic Regulation by D-dimer Reduction | D-dimer (ng/mL) | 28 days | 
| Improved Hemostatic Regulation by reduce PTT | Partial Thromboplastin Time (PTT) Test | 28 days | 
| Average Reduced Viral Load. | Reduced viral load (copies/mL) | 28 days | 
| Average and Categorical Increase in Vitamin D: | 25(OH)D hydroxyvitamin D 1. % of Patients Improving from Critical Deficiency (min. of 20ng/ml); ii. % of Patients Improving from Insufficiency (at min. of 30ng/ml); Active 1,25-dihydroxyvitamin D and i. % of Patients with Improvement from Insufficient (at min. of 18pg/ml); | 28 days | 
| % of Patients with a Change in oxygen requirement | Non-invasive positive pressure support (BiPAP & CPAP) Discharge from the ICU Removal from Ventilator Support | 28 days | 
| Average Temperature | (Average for each day) - Hospital Staff (Highest Record of the day) - Hospital Staff | 28 days | 
| Average Length of Hospitalization | Days in the ICU Days to Discharge Need for Rehospitalization Need for COVID Related Rehospitalization | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Narrow Band Ultraviolet Light B-Band, NB-UVB, Immune Dysregulation, Vitamin D