Clinical trial NCT04610138: Study of ZnAg Liquid Solution to Treat COVID-19 Symptomatic Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Keywords: SARS-CoV-2
COVID
COVID-19
Corona Virus
Lead sponsor: Clene Nanomedicine
Sponsor class: INDUSTRY
Collaborators: name: ICL Pharma
name: Azidus Brazil
First posted: 2020-10-30
Enrollment: 296
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Time to substantial alleviation of COVID-19 symptoms.
timeFrame: Up to 28 days.
Secondary outcomes:
measure: Time to complete alleviation of COVID-19 symptoms.
timeFrame: Up to 28 days.
measure: Proportion of participants who are hospitalized, requires hospitalization or are deceased.
timeFrame: Up to 28 days
Other outcomes:
measure: Number of alive hospital free days at Day 28.
timeFrame: 28 days
measure: Mean change from Baseline to Day 8, Day 14, Day 21, and Day 28 in SARS-CoV-2 viral load.
timeFrame: Up to 28 days
measure: Change from Baseline to Day 8, Day 14, Day 21, and 28 in the slope of oxygen saturation levels (SpO2) assessed per protocol.
timeFrame: up to 28 days
measure: Clinical Global Impression (CGI) Severity and Change measures from Baseline to Day 8, Day 14, Day 21, and 28.
timeFrame: Up to 28 days
measure: Patient Global Impression (PGI) Severity and Change measures from Baseline to Day 8, Day 14, Day 21, and 28.
timeFrame: Up to 28 days
measure: Change in the area under the curve for Net Symptom Burden from Baseline to Day 8, Day 14, Day 21, and 28.
timeFrame: Up to 28 days
measure: Change in clinical status from Baseline to Day 8, Day 14, Day 21, and Day 28.
timeFrame: Up to 28 days
measure: All-cause mortality rate at Day 28.
timeFrame: 28 days
measure: Proportion of subjects who have not returned to "normal" at the day 21 and day 28 visits.
timeFrame: 28 days
Locations:
city: Santo Amaro
country: Brazil
facility: PROCAPE
state: Recife
city: Centro
country: Brazil
facility: Projeto Praca Onze
state: Rio De Janeiro
city: Gloria
country: Brazil
facility: IBPClin
state: Rio De Janeiro
city: Campinas
country: Brazil
facility: Casa de Saúde
state: Sau Paulo
city: Sao Paulo
country: Brazil
facility: IPECC
state: State Of Sau Paulo
Study officials:
References: