Clinical trial NCT05113810: The Potential Use of Nebulized Hydroxychloroquine for the Treatment of COVID-19
Official title: A Pilot, Randomized, Open-label Trial to Determine the Feasibility, Safety, Efficacy, and Pharmacokinetics of Nebulized HCQ01for the Treatment of Patients With COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: 2019 Novel Coronavirus
Keywords: COVID-19
Inhaled/nebulized Hydroxychloroquine
Lead sponsor: Ministry of Health Jordan
Sponsor class: OTHER_GOV
Collaborators: name: King Hussein Cancer Center
name: ACDIMA Biocenter
name: Amman Pharmaceutical Industries
name: Sana Pharmaceutical Industry
First posted: 2021-11-09
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a pilot, randomized, single-center, parallel group, open-label controlled study to evaluate the feasibility, safety, efficacy, and pharmacokinetics of nebulized HCQ01 plus Standard of Care (SOC) versus SOC alone in hospitalized COVID-19 patients. The Jordanian Ministry of Health (MOH) is the study sponsor, and the study will be conducted at MOH COVID-19 hospitals.

Approximately 110 patients, ≥18 years of age with a confirmed SARS-CoV-2 infection, will be enrolled and randomized 1:1 to the treatment and control arms where they will receive ten doses of Hydroxychloroquine solution via nebulizer in addition to SOC or the control arm where treatment will follow the MOH SOC.


Eligibility criteria: Inclusion Criteria:

1. Pregnant (positive β-human chorionic gonadotropin test, β-HCG) or lactating female at screening.
2. Patients with a history of retinopathy, sickle cell disease or trait, psoriasis, porphyria, history of splenectomy, mental illness or uncontrolled seizures disorder, known active tuberculosis or history of incompletely treated tuberculosis, patients on chronic immunosuppression for other medical conditions such as rheumatological disorders, inflammatory bowel disease, or in patients with organ transplants.
3. Patients admitted in ICU.
4. Taking medications which may lead to interactions with hydroxychloroquine, including penicillamine, telbivudine, botulinum toxin, fluconazole, digoxin, propafenone , cimetidine, statins, warfarin, and cyclosporine within 2 weeks of dosing start, and during the duration of the study.
5. History of Glucose-6-phosphate dehydrogenase deficiency.
6. Pre-treatment corrected QT interval (QTc) ≥450 milliseconds.

Exclusion Criteria:

1. Pregnant (positive β-human chorionic gonadotropin test, β-HCG) or lactating female at screening.
2. Patients with a history of retinopathy, sickle cell disease or trait, psoriasis, porphyria, history of splenectomy, mental illness or uncontrolled seizures disorder, known active tuberculosis or history of incompletely treated tuberculosis, patients on chronic immunosuppression for other medical conditions such as rheumatological disorders, inflammatory bowel disease, or in patients with organ transplants.
3. Patients admitted in ICU.
4. Taking medications which may lead to interactions with hydroxychloroquine, including penicillamine, telbivudine, botulinum toxin, fluconazole, digoxin, propafenone , cimetidine, statins, warfarin, and cyclosporine within 2 weeks of dosing start, and during the duration of the study.
5. History of Glucose-6-phosphate dehydrogenase deficiency.
6. Pre-treatment corrected QT interval (QTc) ≥450 milliseconds.
7. Acute or chronic kidney disease (stage-4 or -5 renal impairment; eGFR\<30 mL/min/1.73 m2 or hemodialysis).
8. Liver Child-Pugh grade C.
9. Patients with Hypokalemia (\<3.5mmol/L), Hypocalcemia (\<2.2mmol/L), Hypomagnesemia (\<0.66mmol/L). Will be included after correction.
10. Need for mechanical ventilation.
11. History of hypersensitivity to hydroxychloroquine.
12. History of Chronic Hepatitis B or hepatitis C infections.
13. History of Human Immunodeficiency Virus (HIV) infection.
14. Concurrent serious illness including, but not limited to, any of the following:

    * Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, myocardial infarction, or unstable angina).
    * New York Heart Association class II-IV congestive heart failure.
    * Serious cardiac arrhythmia requiring medication. -Peripheral vascular disease ≥ grade 2 within the past year. -
    * Psychiatric illness/social situation that would limit compliance with study requirements. -COPD, Lung cancer, and moderate to severe asthma.
15. Any other significant finding based on the judgment of the PI would increase the risk of having an adverse outcome from participating in this study.
16. Any other concomitant treatment based on the judgment of the PI would increase the risk of having an adverse outcome from participating in this study.
17. Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 80 days of signing the informed consent/assent for this current trial.

Primary outcomes:
measure: WHO Ordinal Scale for for Clinical Improvement
timeFrame: [ Day -1 (screening) to Days 3,6, and 14 ]
Secondary outcomes:
measure: Proportion of participants who improve by at least one level lower on the 11-point WHO-OSCI
timeFrame: Day 28
measure: All-cause mortality
timeFrame: Day 28
measure: HCQ concentration in plasma versus time profiles
timeFrame: Day 1 pre-dose (within 1-hour prior dosing) and +2, +5, +10, +15, +20, +25, and +30 minutes after dose, and also +1, +2, +3, +4 and +6 hours post-dose completion
measure: Change from Baseline Oxygenation as determined by the SpO2/FiO2 ratio
timeFrame: Days 3 & 6
measure: Rate of Transfer to the Intensive Care Unit
timeFrame: Up to day 28
measure: Time to Hospital Discharge or NEWS2 (National Early Warning Score 2) of ≤ 2
timeFrame: Up to day 28
measure: Treatment-related adverse events of HCQ
timeFrame: Up to day 28
measure: Cardiac Arrhythmia - Polymorphic Ventricular Tachycardia [Time Frame
timeFrame: Up to day 6
measure: Cardiac Arrhythmia - Ventricular Tachycardia
timeFrame: Up to day 6
measure: Cardiac Arrhythmia - Lengthening QTc
timeFrame: Up to day 6
Other outcomes:
Locations:
city: Amman
country: Jordan
facility: Prince Hamza Hospital/ Amman Field Hospital
Study officials:
affiliation: The Jordanian Ministry of Health
name: Feras Hawari, MD
role: PRINCIPAL_INVESTIGATOR
References: