Corona Virus Infection, Covid19, SARS-CoV Infection
Conditions
Keywords
corona, covid19, covid, coronavirus, corona virus infection, sars-cov-2
Brief summary
A preparation of CimertrA, comprising Artemisinin, Curcumin, and Boswellia, and Vitamin C in a nanoparticular formulation, is proposed as a treatment for the disease associated with the novel coronavirus SARS-CoV-2. This initiative is presented under the urgent circumstances of the fulminant pandemic caused by this lethal disease, which is known as COVID-19 and has spread across the globe causing death and disrupting the normal function of modern society. The grounds for the proposal are rooted in existing knowledge on the components and pharmacological features of this formulation and their relevance to the current understanding of the disease process being addressed. The severe acute respiratory syndrome-associated coronavirus disease 2019 (COVID-19) illness results from the immediate response to the viral infection as well as from a subsequent host inflammatory response. Systemic proinflammatory cytokines and biomarkers are elevated as the disease progresses towards its advanced stages, and correlate with worse chances of survival. Serum cytokine levels that are elevated in patients with Covid-19-associated cytokine storm include interleukin-1β, interleukin-6, IP-10, TNF, interferon-γ, macrophage inflammatory protein (MIP) 1α and 1β, and VEGF. Higher interleukin-6 levels are strongly associated with shorter survival. The relative frequencies of circulating activated CD4+ and CD8+ T cells and plasmablasts are increased in Covid-19. In addition to the elevated systemic cytokine levels and activated immune cells, several clinical and laboratory abnormalities, such as elevated CRP and d-dimer levels, hypoalbuminemia, renal dysfunction, and effusions, are also observed in Covid-19. Laboratory test results reflecting hyper inflammation and tissue damage were found to predict worsening outcomes in Covid-19. CimetrA, comprising Artemisinin, Curcumin, Boswellia, and Vitamin C in a nanoparticular formulation, has been studied on patients with COVID-19 in a randomized double-blind control Phase II study (MGC-006 - under a previous product name - ArtemiC). The study product demonstrated excellent safety and efficacy profiles. Experiments performed in vitro with CimetrA demonstrated the ability to reduce cytokine elevation in response to stimulation of human PBMC preparations. The currently proposed Multi-center multinational-controlled study is designed to include 252 adult patients who suffer from moderate COVID-19 infection. Safety will be assessed through collection and analysis of adverse events, blood and urine laboratory assessments, and vital signs. After the screening visit, the study drug will be administrated twice a day morning and evening (every 12 hours) during (day 1 and day 2) The patients will be randomized in 1:1:1 ratio to study drug (CimetrA) in addition to Standard of Care (Arm 1 (CimetrA-1) or Arm 2 (CimetrA-2)) or Placebo in addition to Standard of Care (Arm 3).
Detailed description
The study will take place during the patient's hospitalization due to a COVID-19 infection. The study will last up to 4 weeks, until the conclusion on day 28. In case of hospital discharge within the study period, follow-up will continue per protocol until day 28 wherever the subject will be located, performed via phone call or in-clinic, depending on the status of the patient and study schedule. 252 adult patients who suffer from COVID-19 infection and do not participate in any other clinical trial. The patient must not agree to participate in any new clinical study during the study duration. The study will take place during the patient's hospitalization due to a COVID-19 infection. The study will last up to 4 weeks, until the conclusion on day 28. In case of hospital discharge within the study period, follow-up will continue per protocol until day 28 wherever the subject will be located, performed via phone call or in-clinic, depending on the status of the patient and study schedule. Day 1 Prior to engaging in any study procedures, the subject must meet the inclusion/exclusion criteria by history (which includes a signed declination), and review and sign an ICF. Following procedures will be performed during the visit - * Inclusion/Exclusion criteria evaluation * Informed Consent * Medical History * Concomitant Medications * Physical Examination * Vital Signs * Hematology blood test (local, mandatory even if there are available results from the day before) * Biochemistry blood test (local, mandatory even if there are available results from the day before) * NEWS score * PK test (brazil only, central)\* * Blood test for inflammatory markers (IL-6, IL-1β, IL-12, TNF α, IFN-γ) (local) * D-Dimer test (local) * VAS scale * Urine pregnancy test for women of childbearing potential * ECG * COVID-19-Impact on Quality of Life Questionnaire (will be completed by the staff based on the patient answer) * Randomization in 1:1:1 ratio to study drug (CimetrA) in addition to Standard of Care (Arm 1 (CimetrA-1) or Arm 2 (CimetrA-2)) or Placebo in addition to Standard of Care (Arm 3) * Treatment administration (twice a day, morning and evening) * Test for detection COVID-19 (within 5 days from admission to hospital) Day 2 * Concomitant Medications * AE Assessment * Physical Examination * Vital Signs * Hematology blood test (local, mandatory even if there are available results from the day before) * Biochemistry blood test (local, mandatory even if there are available results from the day before) * NEWS score * Blood test for inflammatory markers (IL-6, IL-1β, IL-12, TNF α, IFN-γ) (local) * D-Dimer test (local) * VAS scale * Treatment administration (twice a day, morning and evening) Days 3-6 * Concomitant Medications * AE assessment * Physical Examination * Vital Signs * Hematology blood test \*\* * Biochemistry blood test \*\* * News score \*\* * Blood test for inflammatory markers (IL-6, IL-1β, IL-12, TNF α, IFN-γ) (local) * VAS scale Day 7 * Concomitant Medications * AE assessment * Physical Examination * Vital Signs * Hematology blood test (local, mandatory even if there are available results from the day before) * Biochemistry blood test (local, mandatory even if there are available results from the day before) * News score * Blood test for inflammatory markers (IL-6, IL-1β, IL-12, TNF α, IFN-γ) (local) * D-Dimer test (local) * VAS scale * COVID-19-Impact on Quality of Life Questionnaire (will be completed by the staff based on the patient answer) Days 8-13 * Concomitant Medications * AE assessment * Physical Examination * Vital Signs * Hematology blood test \*\* * Biochemistry blood test \*\* * News score \*\* * VAS scale Day 14 * Concomitant Medications * AE assessment * Physical Examination * Vital Signs * Hematology blood test (local, mandatory even if there are available results from the day before) * Biochemistry blood test (local, mandatory even if there are available results from the day before) * News score * Blood test for inflammatory markers (IL-6, IL-1β, IL-12, TNF α, IFN-γ) (local) * D-Dimer test (local) * VAS scale * Test for detection COVID-19 * COVID-19-Impact on Quality of Life Questionnaire (will be completed by the staff based on the patient answer) Day 21 (phone visit) * Concomitant Medications * AE assessment * VAS scale * COVID-19-Impact on Quality of Life Questionnaire (will be completed by the staff based on the patient answer) Day 28 - Follow Up (clinic visit) * Concomitant Medications * AE assessment * Physical Examination * Vital Signs * Hematology blood test (local, mandatory even if there are available results from the day before) * Biochemistry blood test (local, mandatory even if there are available results from the day before) * News score * Blood test for inflammatory markers (IL-6, IL-1β, IL-12, TNF α, IFN-γ) (local) * D-Dimer test (local) * VAS scale * Test for detection COVID-19 * Urine pregnancy test for women of childbearing potential * ECG * COVID-19-Impact on Quality of Life Questionnaire (will be completed by the staff based on the patient answer)
Interventions
DRUGPlacebo administration
patients will receive the placebo treatment in addition to Standard of Care
DIAGNOSTIC_TESTConfirm SARS-CoV-2 infection
patients will be tested for SARS-CoV-2 on days 1, 14 and 28
PROCEDUREPhysical Examination
patients will undergo a physical examination on days 1-14 and day 28
PROCEDUREVital Signs
patient's vital signs will be measured on days 1-14 and day 28
DIAGNOSTIC_TESTHematology blood test
patients will provide a blood sample for a hematology blood test on days 1-14 and day 28
DIAGNOSTIC_TESTBiochemistry blood test
patients will provide a blood sample for a biochemistry blood test on days 1-14 and day 28
OTHERNEWS score
patient's NEWS score will be evaluated on days 1-14 and day 28
DIAGNOSTIC_TESTPK test
PK test will be performed on day 1 only (only in Brazil sites)
DIAGNOSTIC_TESTblood test for inflammatory markers
patients will provide a blood sample for an inflammatory markers blood test (IL-6, IL-1β, IL-12, TNF α, IFN-γ) on days 1-7, day 14, and day 28
DIAGNOSTIC_TESTD-dimer test
patients will provide a blood sample for D-dimer blood test on days 1, day 2, day 7, day 14, and day 28
OTHERVAS scale
patient's VAS scale will be evaluated on days 1-14, day 21, and day 28
DIAGNOSTIC_TESTUrine pregnancy test for women of childbearing potential
patients will provide a urine sample for a urine pregnancy test on days 1, and day 28
PROCEDUREECG
patients will undergo an ECG examination on days 1, and day 28
OTHERCOVID-19-Impact on Quality of Life Questionnaire
patients will answer the COVID-19-Impact on Quality of Life Questionnaire on days 1, 7,14,21 and 28
DRUGCimetrA-1
patients will receive the study treatment, CimetrA-1 treatment in addition to Standard of Care
DRUGCimetrA-2
patients will receive the study treatment, CimetrA-2 treatment in addition to Standard of Care
Sponsors
MGC Pharmaceuticals d.o.o
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Patients will be randomized in 1:1:1 ratio to one of the three arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Confirmed SARS-CoV-2 infection (according to nationally authorized laboratory criteria) 2. Hospitalized patient with COVID-19 of moderate stable or worsening severity not requiring ICU admission. 3. Age: 18 years old and above. 4. Subjects must be under observation or admitted to a controlled facility or hospital (home quarantine is not sufficient). 5. Ability to receive treatment by spray into the oral cavity
Exclusion criteria
1. Tube feeding or parenteral nutrition. 2. Patients with scores 5 or above per the Ordinal Scale for Clinical Improvement published by the WHO. (i.e., who need oxygen supply beyond use of nozzles or simple mask) 3. Need for admission to ICU during the present hospitalization at any time prior to completion of the recruitment to the study. 4. Any condition which, in the opinion of the Principal Investigator, would prevent full participation in this trial or would interfere with the evaluation of the trial endpoints.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| clinical improvement in treatment groups | up to 28 days | Time to sustained clinical improvement, defined as a national Early Warning Score 2 (NEWS2) of 2 Maintained for 24 Hours in comparison to routine treatment (measured on days 7, 14, 28) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic profile | up to 28 days | Pharmacokinetic profile of the study drug-AUC(mmol/L·h) |
| evaluation of drug related adverse events | up to 28 days | Percentage of participants with definite or probable drug related adverse events |
| Long term adverse events of COVID-19 | up to 28 days | Long term adverse events of COVID-19 on Day 28 |
| Quality of life of patients | up to 28 days | Quality of life of patients on Days 0, 14 and 28. COVID-19 - Impact on Quality of Life (COV19-QoL) scale questionnaire. The scale was made in order to serve as a tool for controlling the impact of the situation with the COVID19 pandemic in general on findings of various research on mental health.The higher score, the greater impact on quality of life and related domains subjectively perceived by the participants. Scores could be displayed and analyzed for each item separately. recommend the following way of calculating the total score for each participant: summing the scores on all of the items and dividing that result by the number of items (i.e. 6). Hence, the total score will be the average of all the items. The average score is measured between 1-5 scale. |
| oxygen dependency | up to 28 days | Number of participants with depending on oxygen supplementation through day 28 since onset of symptoms |
| change in inflammatory marker levels | up to day 28 | Change in inflammatory marker levels - IL-6, IL-1β, IL-12, TNF α, IFN-γ, CRP, NLR (Neutrophil / Lymphocyte ratio) at days 1, 2, 4, 7, 14, 28 |
| effective dose determination | up to 28 days | Definition of the active dose of CimetrA |
| Incidence of mechanical ventilation | up to 28 days | Incidence of mechanical ventilation |
| Incidence of Intensive Care Unit (ICU) stay during COVID-19 complication | up to 28 days | Incidence of Intensive Care Unit (ICU) stay during COVID-19 complication |
Other
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of secondary infections | up to 28 days | — |
| Course of change in D Dimer levels compared to baseline | up to 28 days | — |
| Duration of mechanical ventilation | up to day 28 | Duration of mechanical ventilation |
Countries
Israel
Outcome results
None listed