Study of ZnAg Liquid Solution to Treat COVID-19 Symptomatic Participants

Phase 2

Completed

• Conditions: Covid19
• Interventions: Drug: CNM-ZnAg; Drug: Placebo

• Registration Number: NCT04610138
• Lead Sponsor: Clene Nanomedicine

Brief Summary

This is a multi-site, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of ZnAg liquid solution in symptomatic participants with acute COVID-19 that are not hospitalized at the time of enrollment.

Detailed Description

This is a multi-site, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of ZnAg liquid solution in symptomatic participants with acute COVID-19 (PCR documented SARS-CoV-2 infection) that are not hospitalized at the time of enrollment (e.g., present to an emergency room without being admitted to the hospital or diagnosed in an outpatient clinic setting).

Participants must have presented with two or more symptoms of acute COVID-19 (within 96 hours prior to the Baseline visit) self-reported as moderate or severe at the Baseline visit, including fever, myalgia, fatigue, chest tightness, chills, cough, diarrhea, gastrointestinal distress, headache, sore throat, congestion or runny nose, ageusia, anosmia, nausea, tingling or numbness in the extremities, or shortness of breath. SARS-CoV-2 infection must be confirmed by polymerase chain reaction (PCR) testing within 96 hours prior to the Baseline visit.

Participants who meet all inclusion criteria and none of the exclusion criteria and who formally consent to participate will be randomized 1:1:2 to receive ZnAg (low dose) : ZnAg (high dose) placebo in a double-blind fashion in addition to standard supportive care. Within the active treatment arm, participants will be randomized to receive either low or high dose ZnAg.

* Active treatment with 60 ml low-dose ZnAg (Zn 6 ug/ml and Ag 10 ug/ml; equivalent to 0.6 mg Ag, 0.36 mg Zn), po q12 hours or;

* Active treatment with 60 ml high-dose ZnAg (Zn 12 ug/ml and Ag 20 ug/ml; equivalent to 1.2 mg Ag, 0.72 mg Zn), po q12 hours;

* 60 ml matching placebo, po q12 hours

Participants who become clinically unstable during the course of the study (e.g., requiring high-flow supplemental oxygen or mechanical ventilatory support) per the judgement of the site investigator will be admitted to a hospital and their clinical status (e.g., vital status, hospitalization status, respiratory status, COVID-19 ordinal scale) will continue to be tracked per protocol.

Study Timeline

• Study First Submitted: 2020-10-28
• Study First Submitted QC: 2020-10-28
• Study First Posted: 2020-10-30
• Study Start: 2021-06-01
• Primary Completion: 2022-05-28
• Study Completion: 2022-10-20
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-30
• Last Update Posted: 2023-04-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 296

Inclusion Criteria

1. Adults, aged 40 - 90 years (inclusive)
2. Acute onset (within 96 hours of the Baseline visit) of two or more COVID-19 symptoms self-rated as moderate-to-severe, including fever, myalgia, fatigue, chest tightness, chills, cough, diarrhea, gastrointestinal distress, headache, sore throat, congestion, or runny nose, ageusia, anosmia, nausea, tingling or numbness in the extremities, or shortness of breath.
3. Laboratory-confirmed SARS-CoV-2 infection as determined by positive PCR in a sample collected ≤ 96 hours prior to the Baseline visit.
4. PGI-Severity and CGI-Severity assessments of 'Mild', 'Moderate, or 'Severe' at the Screening visit (e.g., cannot be 'Normal').
5. Participant (or legally authorized representatives) provides informed consent prior to the initiation of any study procedures.
6. Participant is willing and able to follow all study procedures and assessments according to the study protocol.
7. Participant is able to consume 60 ml of fluid orally twice daily.
8. Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception, not including hormonal contraception from the time of screening through the end of study.

Read More

Exclusion Criteria

1. Unable or unwilling to take ZnAg liquid solution or matching placebo as directed.
2. Hospitalized prior to Baseline for COVID-19 management.
3. Need for hospitalization and/or ventilatory support at Baseline.
4. The emergence of any disease during study, other than COVID-19 that could better explain the participants' signs and symptoms.
5. Severe disease: respiratory distress, or requiring supplemental oxygen, or SpO2 ≤ 93% on room air, or tachypnea (respiratory rate ≥ 30 breaths/min) at Baseline.
6. History or presence of serious or acute heart disease such as uncontrolled cardiac dysrhythmia or arrhythmia, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure (NYHA class 3 or 4).
7. Legal incapacity or limited legal capacity.
8. Women of childbearing potential who do not agree to use either abstinence or at least one primary form of contraception, not including hormonal contraception from the time of screening through the end of the study.
9. Pregnant or breastfeeding.
10. Participation in another clinical study with an investigational product within the prior 12 months (per Resolution 251/1997).

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active treatment with 60 ml high-dose ZnAg	CNM-ZnAg	(Zn 12 ug/ml and Ag 20 ug/ml; equivalent to 1.2 mg Ag, 0.72 mg Zn), po q12 hours;
Active treatment with 60 ml low-dose ZnAg	CNM-ZnAg	(Zn 6 ug/ml and Ag 10 ug/ml; equivalent to 0.6 mg Ag, 0.36 mg Zn), po q12 hours
60 ml matching placebo	Placebo	60 ml matching placebo, po q12 hours

Primary Outcome Measures

Name	Time	Method
Time to substantial alleviation of COVID-19 symptoms.	Up to 28 days.	Time to substantial alleviation of COVID-19 symptoms up to 28-days, over a continuous period ≥ 48 hours (confirmed symptom resolution), defined as PGI-Severity of 'Normal' in Participants whose Baseline PGI-Severity value was 'Mild'; or, a PGI-Severity of 'Normal' or 'Mild' in participants whose Baseline PGI-Severity value was 'Moderate' or 'Severe'.

Secondary Outcome Measures

Name	Time	Method
Proportion of participants who are hospitalized, requires hospitalization or are deceased.	Up to 28 days	Proportion of participants who are hospitalized, require hospitalization, or are deceased from Baseline to Day 28. Hospitalization will be determined by Investigator's clinical judgement. Where applicable, Investigators should follow local recommendations for hospitalization of patients with COVID-19 within their institution.
Time to complete alleviation of COVID-19 symptoms.	Up to 28 days.	Time to complete alleviation of COVID-19 symptoms up to 28- days, over a continuous period ≥ 48 hours (confirmed symptom resolution).

Trial Locations

Locations (5)

IBPClin; 🇧🇷 Gloria, Rio De Janeiro, Brazil

Projeto Praca Onze; 🇧🇷 Centro, Rio De Janeiro, Brazil

PROCAPE; 🇧🇷 Santo Amaro, Recife, Brazil

IPECC; 🇧🇷 Sao Paulo, State Of Sau Paulo, Brazil

Casa de Saúde; 🇧🇷 Campinas, Sau Paulo, Brazil