Trial of Combination Therapy to Treat COVID-19 Infection

A Phase I Double-Blind Randomized Placebo-Controlled Trial of Combination Therapy to Treat COVID-19 Infection

In this trial patients will be treated with either a combination of therapies to treat COVID-19 or a placebo. Treatment will last 10 days, and patients will be followed for 6 months.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronavirus Infection; Covid-19; COVID; Corona Virus Infection; SARS-CoV Infection; SARS-CoV2; Coronavirus-19
• Intervention / Treatment: Drug: Ivermectin; Drug: Doxycycline Hcl; Dietary supplement: Zinc; Dietary supplement: Vitamin D3; Dietary supplement: Vitamin C

Detailed Description

Patients in this trial will undergo treatment for 10 days with either a combination of therapies or placebo. They will then be followed for an additional 20 days.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (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 male or female subjects at least 18 years of age
3. Diabetic and obese (BMI > 30) patients will be included in the Trial but randomization will be stratified.
4. Positive test for COVID-19 by RT-PCR or rapid antigen test at screening
5. Subjects must agree to practice at least two highly effective methods of birth control for the duration of the study. One of these must be a barrier method. Exceptions for females and partners of females that are not of childbearing potential. (e.g. surgically sterilized, post-menopausal)
6. Subjects must agree they will attend the treatment facility daily for 10d in the event of failure to attend, the patient will be visited at their home to collect the nasal swab and review data.

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 > 104.0 degrees F, 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, found in Appendix II
6. Prescription or other antiviral medications
7. Any comorbidities which constitute health risk for the subject including known cardiac arrhythmias - but will be limited to those on hydroxychloroquine
8. Inability to attend daily for 10 days

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: Active Arm; Patients will be treated with a combination of Ivermectin, Doxycycline, Zinc, Vitamin D3 and Vitamin C	Drug: Ivermectin; Treatment days 1, 4, and 8; Other Names: Soolantra, Stromectol, Sklice; Drug: Doxycycline Hcl; 10 day treatment; Other Names: Doxy-100, Monodox, Oracea, Targadox, Acticlate, Morgidox, Avidoxy, Doryx MPC, Mondoxyne NL, Dory; Dietary supplement: Zinc; 10 Day treatment; Other Names: Zinc sulphate; Dietary supplement: Vitamin D3; 10 day treatment; Other Names: cholecalciferol-D3; Dietary supplement: Vitamin C; 10 day treatment; Other Names: L-ascorbic acid
Placebo Comparator: Placebo; Placebo and Vitamin D3, Vitamin C, and Zinc	Dietary supplement: Zinc; 10 Day treatment; Other Names: Zinc sulphate; Dietary supplement: Vitamin D3; 10 day treatment; Other Names: cholecalciferol-D3; Dietary supplement: Vitamin C; 10 day treatment; Other Names: L-ascorbic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Non-Infectivity by RT-PCR	Time to negative RT-PRC result indicating that patient is no longer infective	6 months
Time to Symptom progression in days as measured by NEWS scoring system (National Early Warning Score)	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
Time to Symptom improvement as measured by NEWS scoring system (National Early Warning Score)	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 as measured by Titer	Patients will have serum stored for titer testing to compare antibody levels over time	6 months
Efficacy of Treatment as measured by RT-PCR	Number of patients testing negative for SARS-CoV-2 by RT-PCR after 10 days of treatment	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Treatment as Measured by D-Dimer	Blood D-Dimer levels	6 Months
Safety of Treatment as Measured by Pro-Calcitonin	Blood Pro-Calcitonin levels	6 Months
Safety of Treatment as Measured by C-Reactive Protein	Blood CRP levels	6 Months
Safety of Treatment as Measured by Ferritin	Blood ferritin levels	6 Months
Safety of Treatment as Measured by Liver Enzymes	Blood enzyme levels	6 Months
Safety of Treatment as Measured by Complete Blood Count	CBC	6 Months
Safety of Treatment as Measured by Electrolyte Levels	Blood electrolytes	6 Months
Safety of Treatment as Measured by Treatment Related Adverse Events	Presence or absence of Grade 3 or high treatment related adverse events	6 months

Collaborators and Investigators

• Sponsor: ProgenaBiome
• Collaborators: Topelia Therapeutics
• Investigators: Study Director: Thomas Borody, MD, Topelia Therpeutics

Publications and helpful links

General Publications

• Hazan S, Dave S, Gunaratne AW, Dolai S, Clancy RL, McCullough PA, Borody TJ. Effectiveness of ivermectin-based multidrug therapy in severely hypoxic, ambulatory COVID-19 patients. Future Microbiol. 2022 Mar;17:339-350. doi: 10.2217/fmb-2022-0014. Epub 2022 Feb 9. Erratum In: Future Microbiol. 2022 Sep;17:1091.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2020
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: July 21, 2020
• First Submitted That Met QC Criteria: July 21, 2020
• First Posted (Actual): July 22, 2020

Study Record Updates

• Last Update Posted (Actual): November 2, 2021
• Last Update Submitted That Met QC Criteria: October 26, 2021
• Last Verified: October 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; Severe Acute Respiratory Syndrome; COVID-19; Coronavirus Infections; Infections; Communicable Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Protective Agents; Dermatologic Agents; Trace Elements; Micronutrients; Anti-Bacterial Agents; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antiprotozoal Agents; Antiparasitic Agents; Antioxidants; Antimalarials; Astringents; Vitamin D; Cholecalciferol; Doxycycline; Vitamins; Ascorbic Acid; Ivermectin; Zinc; Zinc Sulfate
• Other Study ID Numbers: PRG-049

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