The Potential Use of Nebulized Hydroxychloroquine for the Treatment of COVID-19

2019 Novel Coronavirus Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05113810
• Other study ID #: 1093-2021
• Status: Recruiting
• Phase: Phase 2
• Start date: March 20, 2022
• Est. completion date: July 20, 2022

Study information

• Verified date: March 2022
• Source: Ministry of Health Jordan
• Contact: Yasmeen Dodin, MSc
• Phone: 00962798950958
• Email: YD.14502[@]KHCC.JO
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: July 20, 2022
• Est. primary completion date: July 20, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Pregnant (positive ß-human chorionic gonadotropin test, ß-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 ß-human chorionic gonadotropin test, ß-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.

Related Conditions & MeSH terms

• 2019 Novel Coronavirus
• COVID-19

Intervention

Drug:
• HCQ01
HCQ01 is a sterile, clear and colorless, ready-to-use aqueous nebulizer solution. Hydroxychloroquine sulfate administered via nebulization

Other:
• standard of care (SOC) for COVID-19
Standard of care (SOC) for COVID-19

Locations

Country	Name	City	State
Jordan	Prince Hamza Hospital/ Amman Field Hospital	Amman

Sponsors (5)

Lead Sponsor	Collaborator
Ministry of Health Jordan	ACDIMA Biocenter, Amman Pharmaceutical Industries, King Hussein Cancer Center, Sana Pharmaceutical Industry

Country where clinical trial is conducted

Jordan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	WHO Ordinal Scale for for Clinical Improvement	Change in condition measured using the Ordinal Scale for Clinical Improvement. Patients are scored on a scale of 0-10 with 0 being uninfected and 10 being dead	[ Day -1 (screening) to Days 3,6, and 14 ]
Secondary	Proportion of participants who improve by at least one level lower on the 11-point WHO-OSCI		Day 28
Secondary	All-cause mortality		Day 28
Secondary	HCQ concentration in plasma versus time profiles		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
Secondary	Change from Baseline Oxygenation as determined by the SpO2/FiO2 ratio		Days 3 & 6
Secondary	Rate of Transfer to the Intensive Care Unit		Up to day 28
Secondary	Time to Hospital Discharge or NEWS2 (National Early Warning Score 2) of = 2		Up to day 28
Secondary	Treatment-related adverse events of HCQ		Up to day 28
Secondary	Cardiac Arrhythmia - Polymorphic Ventricular Tachycardia [Time Frame	Cardiologist Diagnostic Documentation	Up to day 6
Secondary	Cardiac Arrhythmia - Ventricular Tachycardia	Cardiologist Diagnostic Documentation	Up to day 6
Secondary	Cardiac Arrhythmia - Lengthening QTc	Cardiologist Diagnostic Documentation	Up to day 6