The Potential Use of Inhaled Hydroxychloroquine for the Treatment of COVID-19 in Cancer Patients

NCT04731051 | Withdrawn Phase 1

• 1 other identifier: HYDR0121/CCO
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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 cancer patients with COVID-19. King Hussein Cancer Center (KHCC) is the study sponsor, and the study will be conducted at KHCC COVID-19 wards. Approximately 28 cancer 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 KHCC SOC.

Conditions

2019 Novel Coronavirus

Outcome Measures

Primary Outcomes (1)

• Proportion of participants who improve by at least one level lower on the 11-point World Health Organization Ordinal Scale for Clinical Improvement (WHO-OSCI), where patients are scored on a scale of 0-10 with 0 being uninfected and 10 being dead .

  Time Frame: Day 14

Secondary Outcomes (20)

• Proportion of participants who improve by at least one level lower on the 11-point WHO-OSCI

  Days 5, 28

• Change in condition measured using the 11-point WHO-OSCI

  Days 5, 14, 28

• All-cause mortality

  Day 28

• Hydroxychloroquine (HCQ) concentration in plasma versus time profiles

  Day 1 pre-dose (time 0) and +2, +5, +10, +15, +20, +25, and +30 minutes after dose, and also +1, +2, +3, +4 and +6 hours post-dose completion

• Change from Baseline Oxygenation as determined by the SpO2 / FiO2 ratio

  Day 5 of treatment

Study Arms (2)

First Arm (Hydroxychloroquine sulfate, 5 days)

EXPERIMENTAL

Participants will receive continued standard of care therapy (SOC) for COVID-19 together with 2 ml HCQ01 (12.5 mg/ml) twice a day for 5 consecutive days.

Drug: HCQ01; Drug: standard of care (SOC) for COVID-19

Second Arm (Continued Standard of Care (SOC) Therapy)

ACTIVE COMPARATOR

Participants will receive continued standard of care therapy for COVID-19

Drug: standard of care (SOC) for COVID-19

Interventions

HCQ01 DRUG

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

First Arm (Hydroxychloroquine sulfate, 5 days)

standard of care (SOC) for COVID-19 DRUG

Standard of care (SOC) for COVID-19

First Arm (Hydroxychloroquine sulfate, 5 days); Second Arm (Continued Standard of Care (SOC) Therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the patient and/or legally authorized representative. Assent, when appropriate, will be obtained per institutional guidelines.
• Male or female ≥18 years of age at time of enrolment.
• History of/ or active histologically or cytologically confirmed diagnosis of hematological or solid tumor (any type, any stage and any localization).
• Eastern Cooperative Oncology Group (ECOG) Status \< or = 3 (Appendix I).
• Patients must have an active cancer treatment or have completed therapy within 12 months of initiation of protocol specified therapy. This includes:
• Patients with a new cancer diagnosis who have not yet initiated cancer therapy.
• Patients on active or have recently completed cancer-directed therapy including chemotherapy, targeted therapy, radiation therapy, immunotherapy or hormonal therapy amongst others which would not increase the risk of having an adverse outcome from participating in this study.
• Currently hospitalized with laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) collected within one week prior to randomization.
• Initial COVID-19 severity status on the WHO 11-point Ordinal Scale for Clinical Improvement = 4 ("Hospitalized; no oxygen therapy "), = 5 ("Hospitalized; oxygen by mask or nasal prongs "), or 6 ("Hospitalized; oxygen by NIV or high flow ") (Appendix II).
• COVID-19-induced pneumonia evidenced by chest X-ray, computed tomography scan (CT scan) or magnetic resonance scan (MR scan).
• Estimated life expectancy of at least 6 months at hospital admission for COVID-19.
• Patients must be receiving standard of care for SARS-CoV-2.
• Patients must have an assessment of adequate organ function within 28 days prior to enrolment, evidenced by:
• Hemoglobin ≥ 9.0 g / dL.
• Leukometry\> 2,000 / mm3 (\> 2 10E3/ ul).

You may not qualify if:

• Pregnant (positive β-human chorionic gonadotropin test, β-HCG) or lactating female at screening.
• 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.
• Patients admitted in ICU.
• 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.
• History of Glucose-6-phosphate dehydrogenase deficiency.
• Pre-treatment corrected QT interval (QTc) ≥450 milliseconds.
• Acute or chronic kidney disease (stage-4 or -5 renal impairment; eGFR\<30 mL/min/1.73 m2 or hemodialysis).
• Liver Child-Pugh grade C.
• Patients with Hypokalemia (\<3.6 mg/dl), Hypocalcemia (\<8.8 mg/dl), Hypomagnesemia (\<1.7 mg/dl). Will be included after correction.
• Need for mechanical ventilation.
• History of hypersensitivity to hydroxychloroquine.
• History of Chronic Hepatitis B or hepatitis C infections.
• History of Human Immunodeficiency Virus (HIV) infection.
• 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).

Sponsors & Collaborators

• King Hussein Cancer Center: lead
• Amman Pharmaceutical Industries (API): collaborator
• Sana Pharmaceutical Industry: collaborator
• ACDIMA Biocenter: collaborator

Study Sites (1)

King Hussein Cancer Center

Amman, 11941, Jordan

Location

MeSH Terms

Interventions

Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Feras Hawari, MD

  King Hussein Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant in Pulmonary and Critical Care

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: January 29, 2021
• Study Start: October 1, 2022
• Primary Completion: November 1, 2022
• Study Completion: December 1, 2022
• Last Updated: April 7, 2023

Record last verified: 2023-04

Locations

JO (1)