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.

• ClinicalTrials.gov Identifier: NCT04900337
• Recruitment Status: Completed
• First Posted: May 25, 2021
• Last Update Posted: February 28, 2024
• Sponsor: Amorphical Ltd.
• Information provided by (Responsible Party): Amorphical Ltd.

Tracking Information

• First Submitted Date: May 19, 2021
• First Posted Date: May 25, 2021
• Last Update Posted Date: February 28, 2024
• Actual Study Start Date: February 9, 2021
• Actual Primary Completion Date: June 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 23, 2021)

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. [ Time Frame: Treatment Day 1 to Day 21 or discharge from hospital, the earliest. ]

Ordinal 8 points scale:

1. Not hospitalized and no limitations of activities.
2. Not hospitalized, with limitation of activities, home oxygen requirement, or both.
3. Hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care (used if hospitalization was extended for infection-control or other nonmedical reasons).
4. Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (related to Covid-19 or to other medical conditions).
5. Hospitalized, requiring any supplemental oxygen.
6. Hospitalized, requiring noninvasive ventilation or use of high-flow oxygen devices.
7. Hospitalized, receiving invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO).
8. Death.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 23, 2021)

• Duration of Hospital stay [ Time Frame: Date of hospitalization to treatment day 21 or discharge, whichever comes first. ]
  Time to discharge from hospital
• Duration of ICU stay [ Time Frame: Treatment Day 1 to treatment day 21 or discharge, whichever comes first. ]
  Time patient is hospitalized in ICU, if applicable.
• Duration of Mechanical Ventilation Use [ Time Frame: Treatment Day 1 to treatment day 21 or discharge, whichever comes first. ]
  Time the patient requires Mechanical Ventilation (if needed)
• Duration of Oxygen Supplementation [ Time Frame: Treatment Day 1 to treatment day 21 or discharge, whichever comes first. ]
  Time the patient requires Oxygen Supplementation (if needed)
• Duration of No Oxygen use [ Time Frame: Treatment Day 1 to treatment day 21 or discharge, whichever comes first. ]
  Time the patient does not require Oxygen Supplementation
• % of patients to meet ordinal scale of 3 or less [ Time Frame: Treatment Day 1 to treatment day 21 or discharge, whichever comes first. ]
  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).
• % of death [ Time Frame: Treatment Day 1 to treatment day 21 or discharge, whichever comes first. ]
  Proportion of subjects died during the study, if any.
• Frequency and severity of adverse events [ Time Frame: Screening to End of treatment day 21 or discharge, whichever comes first. ]
• Number and percent of patients with hypercalcemia [ Time Frame: Treatment days 4, 7, 11, 17 and 21. ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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.
• Official Title: 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.
• Brief Summary: 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

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:

1. Confirmation SARS-CoV-2 infection
2. Respiratory Function (breathing rate, SpO2 Oxygen Saturation
3. Vital Signs (BP, HR), Temperature
4. Blood Tests
5. 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Covid19

Intervention

• Drug: AMOR 18 Powder & Inhalation
  AMOR Inhalation x 3 times a day, via Circulaire® II AMOR Powder x 4 times a day, sublingual
• Drug: Placebo
  Placebo Inhalation x 3 times a day, via Circulaire® II Placebo Powder x 4 times a day, sublingual

Study Arms

• Experimental: AMOR 18 Powder & Inhalation

  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).

  Intervention: Drug: AMOR 18 Powder & Inhalation
• Placebo Comparator: Placebo

  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.

  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 25, 2024): 66
• Original Estimated Enrollment (submitted: May 23, 2021): 100
• Actual Study Completion Date: June 30, 2023
• Actual Primary Completion Date: June 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Males and females of age ≥ 18 years and ≤ 80 years
2. Signed an Informed Consent
3. Agree to undergo blood tests as per protocol
4. Diagnosed with COVID-19
5. Evidence of lung involvement (by chest X rays or lung US)
6. May or may not need for Supplemental Oxygen at enrollment
7. Hospitalized

Exclusion Criteria:

1. Pregnant or breast-feeding females
2. Patients with non-COVID19 related Pneumonia
3. Any pulmonary disease not related to COVID19
4. Tracheostomy
5. High flow oxygen or non-invasive ventilation (Bipap) or Mechanical ventilation
6. Hypercalcemia defined as calcium or corrected calcium > 10.5mg/dL
7. Hyperphosphatemia defined as > 4.5mg/dL
8. Urine calcium to creatinine ratio >0.14
9. Participating in another clinical study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel

Administrative Information

• NCT Number: NCT04900337
• Other Study ID Numbers: AMCS-COVID-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Amorphical Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Amorphical Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Amorphical Ltd.
• Verification Date: February 2024