Novel Agents for Treatment of High-risk COVID-19 Positive Patients

NCT04374019 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: MCC-20-COVID-01-PMC
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-arm, phase II trial for rapid efficacy and toxicity assessment of multiple therapies immediately after COVID19 positive testing in high-risk individuals. Therapies include stand-alone or combination treatment with hydroxychloroquine, azithromycin, ivermectin, or camostat mesilate, artemesia annua. The hypothesis of this study is that the addition of agents that inhibit viral entry or replication of SARS-CoV-2 virus replication in will be devoid of additional moderate to severe toxicities, will prevent clinical deterioration, and will improve viral clearance in high risk individuals.

Conditions

COVID; Sars-CoV2

Keywords

high-risk

Outcome Measures

Primary Outcomes (1)

• Clinical Deterioration

  Number of patients experiencing clinical deterioration. Clinical deterioration is defined as a less than a 2-point change from the initial COVID 7-Point Ordinal Outcomes Scale within 14 days from the study start. This scale ranges from 1-7. Lower scores indicate worse outcomes (death); higher scores indicate fewer symptoms and better outcomes.

  14 days

Secondary Outcomes (12)

• Change in Viral Load

  40 days

• Rate of Organ Failure

  28 days

• Progression to ICU Care or Ventilation

  28 days

• Number of Participants Who Had a Change in Clinical Status Measured by Decrease in COVID 7-point Ordinal Scale

  14 days

• Mortality

  14 days

Study Arms (4)

Arm C: Ivermectin

EXPERIMENTAL

Ivermectin

Drug: Ivermectin

Arm D: Camostat Mesilate

EXPERIMENTAL

Camostat Mesilate

Drug: Camostat Mesilate

Arm E: Artemesia annua

EXPERIMENTAL

Artemesia annua tea or coffee

Dietary Supplement: Artemesia annua

Arm F: Artesunate

EXPERIMENTAL

Artesunate

Drug: Artesunate

Interventions

Ivermectin DRUG

Ivermectin: Days 1-2: Weight \< 75kg: 4 tabs (12 mg total daily dose) Days 1-2: Weight \> 75kg: 5 tabs (15 mg total daily dose)

Arm C: Ivermectin

Camostat Mesilate DRUG

Days 1-14: 2 tab TID after a meal (600 mg total daily dose)

Arm D: Camostat Mesilate

Artemesia annua DIETARY_SUPPLEMENT

Days 1-14: tea or coffee pod TID (1350 mg total daily dose)

Arm E: Artemesia annua

Artesunate DRUG

Days 1-14:

Arm F: Artesunate

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Laboratory-confirmed SARS-CoV-2 infection within the past 7 days or the presence of symptoms or physical examination signs providing high probability of COVID-19 disease
• Patients must have adequate organ and marrow function measured within the last 6 months
• Subjects must have at least one of the following high-risk features for clinical deterioration:
• Hypertension
• Diabetes Mellitus
• Moderate to severe Chronic Obstructive Pulmonary Disease, Emphysema, Cystic Fibrosis, or Asthma
• Cancer patients who have received any immunosuppressive drugs within a year from enrollment
• Sickle Cell disease or thalessemia
• Age \> or = 50
• BMI \> or = 30
• Living in a nursing home or long-term facility
• Underlying serious heart condition as determined by the treating physician
• Immunocompromised subject as defined by the treating physician or COVID-19 Telehealth Treatment Team

You may not qualify if:

• Severe or life threating COVID
• Weight less than 45 kg.
• Pregnant or breast-feeding females
• Subjects on dialysis or with creatinine clearance \< 45 ml/min
• Existing DMID Toxicity Scale for Determining Severity of Adverse Events grade 3 or greater hepatic failure
• Previously documented moderate or severe retinopathy or macular degeneration
• Uncontrolled Seizure disorder
• Prolonged QT, defined as QTc ≥470 milliseconds for men and as QTc ≥480 for women using Bazett's formula
• Known allergy to artesunate, artemisia annua, hydroxychloroquine, macrolides, 4-aminoquinolines, camostat mesilate, or other agents to be used in the trial.
• Currently receiving any study medications for other indications
• Concurrent use of medication that would cause drug-drug interactions
• Patients with psychiatric illness/social situations that would limit compliance

Sponsors & Collaborators

• Susanne Arnold: lead

Study Sites (1)

University of Kentucky Markey Cancer Center

Lexington, Kentucky, 40532, United States

Location

MeSH Terms

Interventions

Ivermectin; camostat; Artesunate

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons

Limitations and Caveats

Thsi study was closed to accrual due to slow accrual rate. No conclusions on efficacy can be made due to a lack of statistical power in each arm.

Results Point of Contact

• Title: Susanne Arnold MD
• Organization: University of Kentucky

smarno0@uky.edu

8592579568

Study Officials

• Susanne Arnold, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 1, 2020
• First Posted: May 5, 2020
• Study Start: May 1, 2020
• Primary Completion: December 21, 2020
• Study Completion: January 12, 2022
• Last Updated: January 20, 2022
• Results First Posted: January 20, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)