Hydroxychloroquine Monotherapy and in Combination With Azithromycin in Patients With Moderate and Severe COVID-19 Disease

A Multi-center, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Efficacy of Hydroxychloroquine Monotherapy and in Combination With Azithromycin in Patients With Moderate and Severe COVID-19 Disease

Two recent studies have suggested that in patients with Covid19, treatment with hydroxychloroquine may shorten the duration of symptoms and improve viral clearance, an effect that appears most pronounced when combined with azithromycin. Hydroxychloroquine treatment may inhibit viral nucleic acid-mediated activation of various innate immune pathways, as well as blockade of lysosomal functions in cell types relevant for viral entry and antigen presentation.

The purpose of the study was to determine if oral hydroxychloroquine monotherapy, or in combination with azithromycin results in clinical benefit in patients hospitalized with COVID19 pneumonia.

Study Overview

• Status: Completed
• Conditions: Covid-19
• Intervention / Treatment: Drug: Placebo; Drug: HCQ; Drug: HCQ+AZT

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Fullerton, California, United States, 92835
      • Novartis Investigative Site
    • Los Angeles, California, United States, 90095-1793
      • Novartis Investigative Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Novartis Investigative Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Novartis Investigative Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Novartis Investigative Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Novartis Investigative Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Informed consent must be obtained prior to participation in the study
2. Adult patient ≥ 18 years old
3. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test from respiratory tract specimen (e.g nasopharyngeal swab)
4. Onset of signs and symptoms of COVID19 illness ≤ 7 days prior to randomization (including but not limited to fever, cough, myalgias, fatigue, abnormal chest imaging)
5. Currently hospitalized or requiring hospitalization due to COVID-19 disease

Exclusion Criteria:

1. Use of other investigational drugs or newly approved COVID-19 treatments within 5-half lives or 30 days of enrolment
2. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
3. Participation in any other clinical trial of an experimental treatment for COVID-19
4. Expectation of concurrent treatment with any other agents or potential direct acting antiviral activity against SARS-Co V-2 during study drug dosing
5. Requires, in the judgement of the investigator, admission to the intensive care unit (ICU) or mechanical ventilatory support (invasive or non-invasive) prior to first dose of study drug (There might be a patient who cannot be admitted to the ICU, even if the patient's condition is severe enough, due to administrative reasons under the current circumstances. This case is also considered under admission to the ICU judged by the investigator)
6. Evidence of cytokine storm syndrome or multi-organ system failure
7. Confirmed co-infection with influenza
8. Creatinine clearance < 45 mL/min or requiring acute renal replacement therapy
9. History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants participating in the study
10. Any other condition which in the opinion of the investigator, would put the safety of the participant at risk, impede compliance or hinder completion of the study
11. Pregnant or nursing (lactating) women
12. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they agree to use basic methods of contraception during dosing of study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: hydroxychloroquine + aithromycin placebo; Hydroxychloroquine 600mg o.d. as loading dose (Day 1) +followed by 200mg t.i.d was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin (AZT) placebo o.d.	Drug: HCQ; Hydroxychloroquine Monotherapy; Other Names: JWT629
Experimental: Arm 2: hydroxychloroquine + azithromycin; Hydroxychloroquine 600 mg o.d. as a loading dose (Day 1) followed by 200 mg t.i.d. was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin: 500 mg as a loading dose (Day 1) followed by 250 mg o.d. Day 2 - Day 5	Drug: HCQ+AZT; Hydroxychloroquine with azithromycin; Other Names: JWT629 + AZT
Placebo Comparator: Arm 3: hydroxychloroquine placebo + azithromycin placebo; Hydroxychloroquine placebo o.d. (day 1) followed by hydroxychloroquine placebo t.i.d Azythromycin placebo o.d.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieved Clinical Response by Day 15	Clinical response was defined as a) discharged alive; or b) No need for mechanical ventilation in any participants and no need for supplemental oxygen requirement (SpO2) in participants without pre-morbid O2 requirement.	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieved Viral Clearance	Number and percentage of participants with negative or below LLOQ SARS-COV-2 based on polymerase chain reaction (PCR) test	6 days and 10 Days
Number of Participants Discharged or Ready for Discharge	Number of participants who received hydrochloroquine plus azithromycin relative to placebo who were discharged from hospital	15 days
Time to Return to Pre-morbid Supplemental Oxygen Requirement in Participants Receiving Hydrochloroquine or Hydrochloroquine Plus Azithromycin Relative to Placebo	Number of participants requiring supplemental oxygen at the time of randomization who returned to pre-morbid supplemental oxygen	15 days

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Actual): July 27, 2020
• Study Completion (Actual): July 27, 2020

Study Registration Dates

• First Submitted: April 8, 2020
• First Submitted That Met QC Criteria: April 20, 2020
• First Posted (Actual): April 22, 2020

Study Record Updates

• Last Update Posted (Actual): October 11, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; adult; covid19; coronavirus; covid 19; covid-19; novel coronavirus; SARS-CoV; JWT629; acute respiratory syndrome coronavirus
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: CJWT629A12301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No