A Study of Combination Therapies to Treat COVID-19 Infection

A Phase IIa Randomized, Controlled Study of Combination Therapies to Treat COVID-19 Infection

This study seeks to determine whether dual or quadruple therapy is more effective in treating COVID-19.

Study Overview

• Status: Withdrawn
• Conditions: COVID-19; Coronavirus Infection; SARS-CoV 2; COVID; Corona Virus Infection; SARS Pneumonia; Coronavirus-19; Coronavirus Sars-Associated as Cause of Disease Classified Elsewhere
• Intervention / Treatment: Drug: hydroxychloroquine; Drug: Azithromycin; Drug: Ritonavir; Drug: Lopinavir

Detailed Description

In this study, patients will be administered either dual or quadruple therapy and have PCR tests run daily to determine efficacy as indicated by time to non-infectivity

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Ventura, California, United States, 93003
      • ProgenaBiome

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent, demonstrating that the subject understands the procedures required for the study and the purpose of the study
2. Healthy, ambulant male or female subjects 18 years of age to 65 years of age
3. Positive test for COVID-19 by RT-PCR at screening
4. Subjects must agree to practice at least one highly effective method of birth control for the duration of the study. This includes condoms with spermicide, oral birth control pills, contraceptive implants, intra-uterine devices, or diaphragms. Subjects not of reproductive potential will be exempt (e.g. post-menopausal, surgically sterilized)
5. Subjects must agree they will do their best to attend the treatment facility daily for 10 days

Exclusion Criteria:

1. Refusal to sign informed consent form
2. Negative test for COVID-19 by RT-PCR at screening
3. Severe disease symptomatically including pneumonia, respiratory distress, tachypnea, shortness of breath, temperature > 38 degrees; pleuritic pain, or frequent cough.
4. Known drug allergy to any of the investigational medications
5. Currently taking medication with known drug interactions with investigational medications (listed in appendix)
6. Prescription or other antiviral medications
7. Any comorbidities which constitute health risk for the subject
8. Pregnant or lactating females;
9. weight < 110lb;
10. porphyria
11. established retinal disease
12. Inability to attend daily for 10 days

13. Any contraindications for treatment with hydroxychloroquine

    1. Hypoglycemia
    2. Known G6PD deficiency
    3. Porphyria
    4. Anemia
    5. Neutropenia
    6. Alcoholism
    7. Myasthenia gravis
    8. Skeletal muscle disorders
    9. Maculopathy
    10. Changes in visual field
    11. Liver disease
    12. Psoriasis
    13. History of QT >500msec
    14. History of torsades de pointes
14. Anemia from pyruvate kinase and G6PD deficiencies
15. Abnormal EKG with QT prolongation acquired or from birth
16. History of jaundice or high fevers prior to developing COVID-19
17. Treatment with any of the medications listed in Appendix II
18. Treatment with any anti-epileptic medication
19. Treatment with any other drug not listed that affects the QT interval

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dual Therapy; Dual Therapy utilizing hydroxychloroquine and azithromycin.	Drug: hydroxychloroquine; Treatment with the drug hydroxychloroquine; Other Names: Plaquenil; Drug: Azithromycin; Treatment with the drug azithromycin; Other Names: Zithromax
Experimental: Quadruple Therapy; Quadruple therapy utilizing hydroxychloroquine, lopinavir, ritonavir, and azithromycin	Drug: hydroxychloroquine; Treatment with the drug hydroxychloroquine; Other Names: Plaquenil; Drug: Azithromycin; Treatment with the drug azithromycin; Other Names: Zithromax; Drug: Ritonavir; Treatment with the drug ritonavir; Other Names: norvir; Drug: Lopinavir; Treatment with the drug lopinavir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of Treatment by Reduced Symptoms NEWS (National Early Warning System) scores	Time to reduced symptoms in each treatment group as indicated by NEWS scores, which rate patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.	6 months
Efficacy of Treatment by Time to Non-Infectivity	Time to non-infectivity as measured by PCR testing	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Dual Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) sores	Patient symptoms will be recorded using the NEWS system, which rates patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.	6 months
Safety of Quadruple Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) scores.	Patient symptoms will be recorded using the NEWS system, which rates patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.	6 months
Safety of Dual Therapy as Measured by Complete Blood Count	Changes in blood parameters measured in a Complete Blood Count (CBC).	6 months
Safety of Quadruple Therapy as Measured by Complete Blood Count	Changes in blood parameters measured in a Complete Metabolic Panel.	6 months
Safety of Dual Therapy as Measured by Metabolic Panel -Albumin	Changes in serum albumin levels	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - Albumin	Changes in serum albumin levels	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - A/G Ratio	Changes in serum albumin/globulin ratio	6 months
Safety of Dual Therapy as Measured by Metabolic Panel A/G Ratio	Changes in serum albumin/globulin ratio	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - Alkaline Phosphatase	Changes in serum alkaline phosphatase levels	6 months
Safety of Dual Therapy as Measured by Metabolic Panel Alkaline Phosphatase	Changes in serum alkaline phosphatase levels	6 months
Safety of Dual Therapy as Measured by Metabolic Panel - AST	Changes in serum AST levels	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - AST	Changes in serum AST levels	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - ALT	Changes in serum ALT levels	6 months
Safety of Dual Therapy as Measured by Metabolic Panel ALT	Changes in serum ALT levels	6 months
Safety of Dual Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio	Changes in serum BUN/Creatinine Ratio	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio	Changes in serum BUN/Creatinine Ratio	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - BUN	Changes in serum Blood Urea Nitrogen levels	6 months
Safety of Dual Therapy as Measured by Metabolic Panel - BUN	Changes in serum Blood Urea Nitrogen levels	6 months
Safety of Dual Therapy as Measured by Metabolic Panel - Calcium	Changes in serum calcium levels	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - Calcium	Changes in serum calcium levels	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - Carbon Dioxide	Changes in serum carbon dioxide levels	6 months
Safety of Dual Therapy as Measured by Metabolic Panel - Carbon Dioxide	Changes in serum carbon dioxide levels	6 months
Safety of Dual Therapy as Measured by Metabolic Panel - Chloride	Changes in serum chloride levels	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - Chloride	Changes in serum chloride levels	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - Creatinine	Changes in serum creatinine levels	6 months
Safety of Dual Therapy as Measured by Metabolic Panel - Creatinine	Changes in serum creatinine levels	6 months
Safety of Dual Therapy as Measured by Metabolic Panel - Globulin	Changes in serum globulin levels	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - Globulin	Changes in serum globulin levels	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - Glucose	Changes in blood glucose levels	6 months
Safety of Dual Therapy as Measured by Metabolic Panel - Glucose	Changes in blood glucose levels	6 months
Safety of Dual Therapy as Measured by Metabolic Panel - Potassium	Changes in blood potassium levels	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - Potassium	Changes in blood potassium levels	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Bilirubin	Changes in serum total bilirubin levels	6 months
Safety of Dual Therapy as Measured by Metabolic Panel - Total Bilirubin	Changes in serum total bilirubin levels	6 months
Safety of Dual Therapy as Measured by Metabolic Panel - Total Protein	Changes in serum total protein levels	6 months
Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Protein	Changes in serum total protein levels	6 months
Safety of Dual Therapy as Measured by Treatment Related SAE	Presence or absence of treatment related serious adverse events Grade III or higher	6 months
Safety of Quadruple Therapy as Measured by Treatment Related SAE	Presence or absence of treatment related serious adverse events Grade III or higher	6 months

Collaborators and Investigators

• Sponsor: ProgenaBiome
• Collaborators: Big Corona Ltd.
• Investigators: Principal Investigator: Thomas Borody, MD, PhD,, Big Corona Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2020
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: June 25, 2020
• First Submitted That Met QC Criteria: July 4, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Coronavirus Infections; Infections; Communicable Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antirheumatic Agents; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; HIV Protease Inhibitors; Viral Protease Inhibitors; Antimalarials; Ritonavir; Lopinavir; Azithromycin; Hydroxychloroquine
• Other Study ID Numbers: PRG-043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No