Azithromycin Plus Hydroxychloroquine for COVID-19 Infection

• ClinicalTrials.gov Identifier: NCT05026801
• Recruitment Status: Withdrawn
• First Posted: August 30, 2021
• Last Update Posted: October 28, 2021
• Sponsor: Iterum Therapeutics, International Limited
• Collaborator: Waterbury Hospital
• Information provided by (Responsible Party): Iterum Therapeutics, International Limited

Tracking Information

• First Submitted Date: February 8, 2021
• First Posted Date: August 30, 2021
• Last Update Posted Date: October 28, 2021
• Actual Study Start Date: February 8, 2021
• Actual Primary Completion Date: August 26, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 26, 2021)

Microbiologic response [ Time Frame: Day 3 (+/- 1 day) ]

Presence or absence of SARS-CoV-2 by PCR on nasopharyngeal specimen

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 26, 2021)

Combined clinical and microbiologic response [ Time Frame: Day 3 (+/- 1 day) ]

Presence or absence of SARS-CoV-2 by PCR on nasopharyngeal specimen and improvement in at least two of the signs and symptoms of RTI

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Azithromycin Plus Hydroxychloroquine for COVID-19 Infection
• Official Title: A Randomized, Double-blinded Phase 3 Multi-center Study of the Clinical and Microbiologic Efficacy of a Combination of Azithromycin and Hydroxychloroquine for Treatment of COVID-19 Infection

Brief Summary

This is a randomized, double-blinded, Phase 3, multi-center trial of the clinical and microbiologic response of patients with a respiratory tract infection (RTI) due to coronavirus treated with a combination of azithromycin and hydroxychloroquine.

Approximately 200 patients with symptoms of an RTI who test positive for SARS-CoV-2 by polymerase chain reaction (PCR) will receive a combination of azithromycin 500 mg and hydroxychloroquine 600 mg or matching placebos for six consecutive days. There will be two treatment regimens into which patients are randomized so that all patients will receive some active therapy.

• Detailed Description: As of March 22, 2020, a total of 311,988 people worldwide have been diagnosed with a respiratory infection caused by SARS-CoV-2 of whom 13,407 have died. In the United States 26,747 patients have tested positive of whom 340 have died. There is at present no established therapy for this infection. After the SARS epidemic in 2002, investigations identified chloroquine as a possible inhibitor of replication of this coronavirus. When the SARS-CoV-2 epidemic started in December of 2019, clinicians began to use chloroquine in an attempt to control the infection in newly diagnosed patients. Investigators from China reported chloroquine phosphate has apparent efficacy in treatment of pneumonia due to SARS-CoV-2. Following this report, investigators in France initiated an open label study of hydroxychloroquine, with the addition of azithromycin, in a small number of subjects with SARS-CoV-2 infection. Relative to no treatment the investigators identified a significant reduction in viral isolation by PCR in the nasal swabs of treated patients, with an additional effect seen when patients were also given azithromycin. Azithromycin, like chloroquine, is a weak base that concentrates in endosomes and lysosomes and raises the pH in those vesicles. It is possible that azithromycin and chloroquine's effect on endosomal processing reduces the inflammatory response by affecting TLR4 signaling through the endosomes.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Approximately 200 patients with symptoms of a RTI who test positive for SARS-CoV-2 by polymerase chain reaction (PCR) will receive a combination of azithromycin 500 mg and chloroquine 500 mg or matching placebos for six consecutive days. There will be two treatment regimens into which patients are randomized so that all patients will receive some active therapy. A sequential probability ratio test will be employed in which comparisons between each regimen will be made with every Day 3 PCR endpoint; if the p value crosses a p=0.001 threshold for any pairwise comparison, the less efficacious arm will be closed to further enrollment and superiority will be declared.

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

Double-blinded

Primary Purpose: Treatment

• Condition: Respiratory Tract Infection Viral

Intervention

Drug: Azithromycin plus hydroxychloroquine

All patients will receive active comparator. One group will receive placebo on D1-3 followed by active comparator D4-9, while the other group will receive active comparator D1-6 followed by placebo D7-9.

Other Name: Placebo

Study Arms

• Active Comparator: Azithromycin plus hydroxychloroquine
  Azithromycin 500 mg plus hydroxychloroquine 600 mg by mouth daily for six consecutive days
  Intervention: Drug: Azithromycin plus hydroxychloroquine
• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Azithromycin plus hydroxychloroquine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: August 26, 2021): 0
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: August 26, 2021
• Actual Primary Completion Date: August 26, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Adults ≥18 years of age

2. History of a respiratory tract infection (RTI) for more than one but less than six days including two or more of the following signs and symptoms of an RTI:

   • Fever (T ≥ 38.0 C, 100.5 F), cough, sputum production, arthralgia/myalgia, anosmia/ageusia or difficulty breathing.

3. A nasal or throat swab or nasal wash positive by PCR for SARS-CoV-2.
4. Has given written informed consent to participate in the study. Due to the public health issues related to this viral infection, witnessed informed consent may be obtained remotely.

Exclusion Criteria:

Exclusion Criteria:

1. Patients likely, in the opinion of the investigator, to require hospitalization within 48 hours of randomization into the study.
2. Concurrent use of non-study antibacterial drug therapy that would have a potential effect on outcome evaluations in patients with an RTI
3. Concurrent use of any other medications for the purpose of treating a viral infection such as influenza antivirals
4. Inability to swallow oral medication in tablet form
5. Patient has severe chronic kidney disease, or is receiving hemodialysis, or peritoneal dialysis or had a renal transplant
6. Patient is known to have severe neutropenia
7. Patients with a known prolongation of the QT interval or are taking medications which could prolong the QT interval
8. Patient is known to be pregnant
9. Patients with a known history of myasthenia gravis
10. Patients with a history of allergy to azithromycin, hydroxychloroquine or chloroquine
11. Patient is considered unlikely to survive the study period or has a rapidly progressive or terminal illness, including septic shock, associated with a high risk of mortality

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05026801
• Other Study ID Numbers: IT005-501
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Deidentified individual participant data for all primary and secondary outcome measures will be made available.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: Data will be available within 30 days of study completion.
• Access Criteria: Data access requests will be reviewed on a case by case basis. Requestors will be required to sign a Data Access Agreement.
• URL: http://www.iterumtx.com

• Current Responsible Party: Iterum Therapeutics, International Limited
• Original Responsible Party: Same as current
• Current Study Sponsor: Iterum Therapeutics, International Limited
• Original Study Sponsor: Same as current
• Collaborators: Waterbury Hospital

Investigators

• Principal Investigator: Michael Dunne, MD; Iterum Therapeutics

• PRS Account: Iterum Therapeutics, International Limited
• Verification Date: October 2021