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

Covid19 Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of ZnAg Liquid Solution to Treat COVID-19 in Acutely Symptomatic Non-Hospitalized Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04610138
• Other study ID #: CNMZnAg.202
• Status: Completed
• Phase: Phase 2
• Start date: June 1, 2021
• Est. completion date: October 20, 2022

Study information

• Verified date: March 2023
• Source: Clene Nanomedicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 296
• Est. completion date: October 20, 2022
• Est. primary completion date: May 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 90 Years

Eligibility

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.

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).

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Drug:
• CNM-ZnAg
ZnAg liquid solution
• Placebo
Water

Locations

Country	Name	City	State
Brazil	Casa de Saúde	Campinas	Sau Paulo
Brazil	Projeto Praca Onze	Centro	Rio De Janeiro
Brazil	IBPClin	Gloria	Rio De Janeiro
Brazil	PROCAPE	Santo Amaro	Recife
Brazil	IPECC	Sao Paulo	State Of Sau Paulo

Sponsors (3)

Lead Sponsor	Collaborator
Clene Nanomedicine	Azidus Brazil, ICL Pharma

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of alive hospital free days at Day 28.	Days from baseline participant remains alive.	28 days
Other	Mean change from Baseline to Day 8, Day 14, Day 21, and Day 28 in SARS-CoV-2 viral load.	Mean change from Baseline to Day 8, Day 14, Day 21, and Day 28 in SARS-CoV-2 viral load (Cycle Thresholds, Ct) , and time to non-detectable virus levels assessed by RT-qPCR.	Up to 28 days
Other	Change from Baseline to Day 8, Day 14, Day 21, and 28 in the slope of oxygen saturation levels (SpO2) assessed per protocol.	Oxygen saturation will be obtained after the participant has been resting for 5 minutes.	up to 28 days
Other	Clinical Global Impression (CGI) Severity and Change measures from Baseline to Day 8, Day 14, Day 21, and 28.	Measured by changes in participant rated Clinical Global Impression.	Up to 28 days
Other	Patient Global Impression (PGI) Severity and Change measures from Baseline to Day 8, Day 14, Day 21, and 28.	Measured by changes in participant rated Patient Global Impression.	Up to 28 days
Other	Change in the area under the curve for Net Symptom Burden from Baseline to Day 8, Day 14, Day 21, and 28.	Summary measure integrating semi-daily serial assessments of a subject's symptom count and severity over the duration of the study.	Up to 28 days
Other	Change in clinical status from Baseline to Day 8, Day 14, Day 21, and Day 28.	Assessed by the Clinical Status Ordinal Scale established in the remdesivir ACTT study. Scale is 1-8, with 1 being the least severe and 8 being the most severe (death).	Up to 28 days
Other	All-cause mortality rate at Day 28.	Rate of deceased participants at day 28.	28 days
Other	Proportion of subjects who have not returned to "normal" at the day 21 and day 28 visits.	Proportion of subjects who do not have a PGI-Severity or CGI-Severity assessment of "normal" at the day 21 and day 28 visits.	28 days
Primary	Time to substantial alleviation of COVID-19 symptoms.	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'.	Up to 28 days.
Secondary	Time to complete alleviation of COVID-19 symptoms.	Time to complete alleviation of COVID-19 symptoms up to 28- days, over a continuous period = 48 hours (confirmed symptom resolution).	Up to 28 days.
Secondary	Proportion of participants who are hospitalized, requires hospitalization or are deceased.	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.	Up to 28 days