Safety, Tolerability and Efficacy of Amorphous Calcium Carbonate (ACC) Compared to Placebo and Best Available Care (BAT), for the Treatment of Moderate to Severe COVID-19 Patients.

Study Overview
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Brief Summary
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This is a phase I/II study with Amorphous Calcium Carbonate (ACC) administered sublingual and in Inhalation concomitantly with BAT (Best Available Care) as Compared to Placebo and BAT for the treatment of Moderate to Severe COVID-19 patients. The purpose of this study is to assess the Safety, Tolerability and Efficacy of Amorphous Calcium Carbonate (ACC).

Detailed Description
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This study includes two parts: Part 1 - A training period of a single arm active treatment open label, to assess the optimal method of study drug administration, as well as the safety of the combined administration, on 5 patients. Following DSMB review of the data collected in part 1 and the DSMB approval to proceed to next part, part 2 will be initiated. Part 2 - A randomized (1:1) placebo controlled 2 arms study. Additional 95 patients will be recruited to this arm. Patients who are hospitalized due to moderate or severe COVID-19 will be recruited to this study. The following elements are the main elements that will be assessed: Confirmation SARS-CoV-2 infection Respiratory Function (breathing rate, SpO2 Oxygen Saturation Vital Signs (BP, HR), Temperature Blood Tests Disease Severity Scale (8 points ordinal scale) The whole study period per patient will be 22 days (21 treatment days) or until the patient has recovered and/or is discharged from the hospital, whichever comes first.

Official Title
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A Phase 1/2 Prospective Randomized Placebo Controlled Study to Assess the Safety, Tolerability and Efficacy of Amorphous Calcium Carbonate (ACC) Administered Sublingual and in Inhalation Concomitantly With BAT (Best Available Care) as Compared to Placebo and BAT for the Treatment of Moderate to Severe COVID-19 Patients.

Conditions
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Covid19

Intervention / Treatment
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* Drug: AMOR 18 Powder & Inhalation
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females of age ≥ 18 years and ≤ 80 years Signed an Informed Consent Agree to undergo blood tests as per protocol Diagnosed with COVID-19 Evidence of lung involvement (by chest X rays or lung US) May or may not need for Supplemental Oxygen at enrollment Hospitalized Exclusion Criteria: Pregnant or breast-feeding females Patients with non-COVID19 related Pneumonia Any pulmonary disease not related to COVID19 Tracheostomy High flow oxygen or non-invasive ventilation (Bipap) or Mechanical ventilation Hypercalcemia defined as calcium or corrected calcium > 10.5mg/dL Hyperphosphatemia defined as > 4.5mg/dL Urine calcium to creatinine ratio >0.14 Participating in another clinical study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMOR 18 Powder & Inhalation<br>AMOR_inhaled Double Pack- Each kit contains two tubes that after mixing result with 1.14 % ACC in 10 ml suspension. AMOR_powder- ACC in a dry powder (up to 2000mg Calcium/day sublingually). | Drug: AMOR 18 Powder & Inhalation<br>* AMOR Inhalation x 3 times a day, via Circulaire® II AMOR Powder x 4 times a day, sublingual<br>|
| Placebo Comparator: Placebo<br>Placebo_Inhaled Double Pack - Each kit contains two tubes of saline at different volumes (similar to investigational product) after mixing the results remains saline at a final volume of 10ml. Placebo_Powder: Each sachet contains powder at the same particle size and weight as the powder of the investigational product. | Drug: Placebo<br>* Placebo Inhalation x 3 times a day, via Circulaire® II Placebo Powder x 4 times a day, sublingual<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Severity rating of Disease using an 8-point ordinal scale on days 7, 14, 21, measured as improvement greater than or equal to 1 point from baseline score. | Ordinal 8 points scale: Not hospitalized and no limitations of activities. Not hospitalized, with limitation of activities, home oxygen requirement, or both. Hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care (used if hospitalization was extended for infection-control or other nonmedical reasons). Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (related to Covid-19 or to other medical conditions). Hospitalized, requiring any supplemental oxygen. Hospitalized, requiring noninvasive ventilation or use of high-flow oxygen devices. Hospitalized, receiving invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). Death. | Treatment Day 1 to Day 21 or discharge from hospital, the earliest. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Hospital stay | Time to discharge from hospital | Date of hospitalization to treatment day 21 or discharge, whichever comes first. | 
| Duration of ICU stay | Time patient is hospitalized in ICU, if applicable. | Treatment Day 1 to treatment day 21 or discharge, whichever comes first. | 
| Duration of Mechanical Ventilation Use | Time the patient requires Mechanical Ventilation (if needed) | Treatment Day 1 to treatment day 21 or discharge, whichever comes first. | 
| Duration of Oxygen Supplementation | Time the patient requires Oxygen Supplementation (if needed) | Treatment Day 1 to treatment day 21 or discharge, whichever comes first. | 
| Duration of No Oxygen use | Time the patient does not require Oxygen Supplementation | Treatment Day 1 to treatment day 21 or discharge, whichever comes first. | 
| % of patients to meet ordinal scale of 3 or less | Proportion of subjects hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care (used if hospitalization was extended for infection-control or other nonmedical reasons). | Treatment Day 1 to treatment day 21 or discharge, whichever comes first. | 
| % of death | Proportion of subjects died during the study, if any. | Treatment Day 1 to treatment day 21 or discharge, whichever comes first. | 
| Frequency and severity of adverse events |  | Screening to End of treatment day 21 or discharge, whichever comes first. | 
| Number and percent of patients with hypercalcemia |  | Treatment days 4, 7, 11, 17 and 21. |