Development and Validation of Ready-to-Use Inhalable Forms of Hydroxychloroquine for Treatment of COVID-19

Study Overview
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Brief Summary
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In this project, we aimed at developing new Ready-to-Use inhalable forms of HCQ that can be used directly through nebulization or using dry powder inhalers (DPIs). These inhaled forms would allow a simple and direct delivery of the drug (HCQ) specifically towards the throat and the lung which are the main sites for the COVID-19 viral infection. Hence, the drug can be available at higher concentrations in the throat and lungs as compared with the currently used treatment protocols, while minimizing the drug systemic concentrations and its presence in other body organs, and thus enhancing the drug efficacy with significantly limiting its side effects. Besides, using inhalable forms can be more convenient to patients suffering from gastrointestinal complications from the disease that can limit the absorption of oral forms. Moreover, the proposed inhalable forms are designed in such a way to hide the drug from the immune system (confer stealth characteristics) using FDA-approved excipients to minimize/avoid any immune response towards the drug as was noted towards it in its oral form that's used in the treatment protocol of COVID-19. In addition, the inhaled formulations will be designed to maintain the overall simplicity and scalability of the preparation which is critical during this urgent pandemic situation. The cost of the final formulation is also taken into consideration since the drug is intended for treatment of thousands or probably millions of patients around the world including countries with limited economic capabilities.

Official Title
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Development and Validation of Ready-to-Use Inhalable Forms of Hydroxychloroquine for Treatment of COVID-19

Conditions
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Covid19, Hydroxychloroquine Adverse Reaction

Intervention / Treatment
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* Drug: inhalable hydroxychloroquine (HCQ)
* Drug: supportive and symptomatic treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 year Laboratory (RT-PCR) positive of SARS-COV-2 (Moderate cases) Chest CT with pneumonia. SaO2/SPO2 ratio > 93% or PaO2/FIO2 ratio > 300 mmHg under the condition in the hospital room. Welling to participate and able to give fully informed consent Exclusion Criteria: Severe and critical illness. Retinopathy and other retinal diseases. Arrhythmias. QT ≥ 400 msec Receiving cardiac drugs Severe liver disease. Pregnancy or lactation. Previous treatment of COVID-19.

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: Crossover Assignment
Interventional Model Description: The first 20 consecutive patients (group A) will be treated by oral antibiotics, supportive treatment and inhalable hydroxychloroquine (HCQ). (In day 1, an inhaled hydroxychloroquine sulfate dose of 12 mg will be taken via nebulization three times/day (TID) as a loading dose. Then, starting from day 2, same dose of 12 mg of inhaled hydroxychloroquine will be taken twice/day (BID) as maintenance dose for 5 days. The subsequent 20 consecutive patients (group B) will receive the same treatment of group A but without inhalable hydroxychloroquine (HCQ). At day 7, all patients of both groups will be evaluated by clinical, laboratory and chest CT parameters. Patients of group B who still show no clinical, laboratory or radiological improvement will continue treatment by adding inhalable hydroxychloroquine (HCQ). for another 7 days and re-evaluated at day 14. Patients of group A who still show no significant improvement at day 7 only will be re-checked at day 14.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: inhalable hydroxychloroquine (HCQ).<br>supportive and symptomatic treatment and inhalable hydroxychloroquine (HCQ). | Drug: inhalable hydroxychloroquine (HCQ)<br>* inhalable hydroxychloroquine (HCQ) plus supportive and symptomatic treatment<br>|
| Placebo Comparator: Placebo<br>supportive and symptomatic treatment | Drug: supportive and symptomatic treatment<br>* supportive and symptomatic treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical recovery defined as 3 days afebrile with improved cough and other clinical signs | Time is measured in hours | 15 days | 
| Time to achieve viral clearance state determined by two successive negative PCR results for two oropharyngeal swabs separated by 48 hours. | Time is measured in hours | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | measuring and monitoring the complication between groups | 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid19, Hydroxychloroquine