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

NCT04358081 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: CJWT629A12301
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Covid-19

Keywords

covid19; covid 19; covid-19; coronavirus; SARS-CoV; SARS-CoV-2; novel coronavirus; adult; JWT629; acute respiratory syndrome coronavirus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Number of Participants Who Achieved Viral Clearance

  6 days and 10 Days

• Number of Participants Discharged or Ready for Discharge

  15 days

• Time to Return to Pre-morbid Supplemental Oxygen Requirement in Participants Receiving Hydrochloroquine or Hydrochloroquine Plus Azithromycin Relative to Placebo

  15 days

Study Arms (3)

Arm 1: hydroxychloroquine + aithromycin placebo

EXPERIMENTAL

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

Arm 2: hydroxychloroquine + azithromycin

EXPERIMENTAL

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

Arm 3: hydroxychloroquine placebo + azithromycin placebo

PLACEBO COMPARATOR

Hydroxychloroquine placebo o.d. (day 1) followed by hydroxychloroquine placebo t.i.d Azythromycin placebo o.d.

Drug: Placebo

Interventions

HCQ DRUG

Hydroxychloroquine Monotherapy

Also known as: JWT629

Arm 1: hydroxychloroquine + aithromycin placebo

HCQ+AZT DRUG

Hydroxychloroquine with azithromycin

Also known as: JWT629 + AZT

Arm 2: hydroxychloroquine + azithromycin

Placebo DRUG

Placebo

Arm 3: hydroxychloroquine placebo + azithromycin placebo

Eligibility Criteria

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

You may qualify if:

• Informed consent must be obtained prior to participation in the study
• Adult patient ≥ 18 years old
• Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test from respiratory tract specimen (e.g nasopharyngeal swab)
• 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)
• Currently hospitalized or requiring hospitalization due to COVID-19 disease

You may not qualify if:

• Use of other investigational drugs or newly approved COVID-19 treatments within 5-half lives or 30 days of enrolment
• History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
• Participation in any other clinical trial of an experimental treatment for COVID-19
• Expectation of concurrent treatment with any other agents or potential direct acting antiviral activity against SARS-Co V-2 during study drug dosing
• 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)
• Evidence of cytokine storm syndrome or multi-organ system failure
• Confirmed co-infection with influenza
• Creatinine clearance \< 45 mL/min or requiring acute renal replacement therapy
• History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants participating in the study
• 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
• Pregnant or nursing (lactating) women
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

Novartis Investigative Site

Fullerton, California, 92835, United States

Location

Novartis Investigative Site

Los Angeles, California, 90095-1793, United States

Location

Novartis Investigative Site

Chicago, Illinois, 60612, United States

Location

Novartis Investigative Site

Baton Rouge, Louisiana, 70809, United States

Location

Novartis Investigative Site

Baltimore, Maryland, 21287, United States

Location

Novartis Investigative Site

Chapel Hill, North Carolina, 27599, United States

Location

Novartis Investigative Site

Seattle, Washington, 98104, United States

Location

Related Links

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

MeSH Terms

Conditions

COVID-19; Coronavirus Infections; Severe Acute Respiratory Syndrome

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Only 20 participants of the initially planned 444 were randomized; and one of those was mis-randomized (so total of 19 participants). Due to this limited number of participants, study objectives could not be evaluated as planned. Results for select efficacy and for safety were summarized based in the information collected up to the eCRF database lock on 13-Aug-2020.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+1 (862) 778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2020
• First Posted: April 22, 2020
• Study Start: May 1, 2020
• Primary Completion: July 27, 2020
• Study Completion: July 27, 2020
• Last Updated: October 11, 2021
• Results First Posted: March 17, 2021

Record last verified: 2021-10

Locations

US (7)