A preparation of CimertrA, comprising Artemisinin, Curcumin, and Boswellia, and Vitamin Cin a nanoparticular formulation, is proposed as a treatment for the disease associatedwith the novel coronavirus SARS-CoV-2. This initiative is presented under the urgentcircumstances of the fulminant pandemic caused by this lethal disease, which is known asCOVID-19 and has spread across the globe causing death and disrupting the normal functionof modern society. The grounds for the proposal are rooted in existing knowledge on thecomponents and pharmacological features of this formulation and their relevance to thecurrent 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 asubsequent host inflammatory response. Systemic proinflammatory cytokines and biomarkersare elevated as the disease progresses towards its advanced stages, and correlate withworse chances of survival.Serum cytokine levels that are elevated in patients with Covid-19-associated cytokinestorm include interleukin-1β, interleukin-6, IP-10, TNF, interferon-γ, macrophageinflammatory protein (MIP) 1α and 1β, and VEGF. Higher interleukin-6 levels are stronglyassociated 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 elevatedsystemic cytokine levels and activated immune cells, several clinical and laboratoryabnormalities, such as elevated CRP and d-dimer levels, hypoalbuminemia, renaldysfunction, and effusions, are also observed in Covid-19. Laboratory test resultsreflecting hyper inflammation and tissue damage were found to predict worsening outcomesin Covid-19.CimetrA, comprising Artemisinin, Curcumin, Boswellia, and Vitamin C in a nanoparticularformulation, has been studied on patients with COVID-19 in a randomized double-blindcontrol Phase II study (MGC-006 - under a previous product name - ArtemiC). The studyproduct demonstrated excellent safety and efficacy profiles.Experiments performed in vitro with CimetrA demonstrated the ability to reduce cytokineelevation in response to stimulation of human PBMC preparations.The currently proposed Multi-center multinational-controlled study is designed to include252 adult patients who suffer from moderate COVID-19 infection. Safety will be assessedthrough collection and analysis of adverse events, blood and urine laboratoryassessments, and vital signs.After the screening visit, the study drug will be administrated twice a day morning andevening (every 12 hours) during (day 1 and day 2) The patients will be randomized in1:1:1 ratio to study drug (CimetrA) in addition to Standard of Care (Arm 1 (CimetrA-1) orArm 2 (CimetrA-2)) or Placebo in addition to Standard of Care (Arm 3).
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)
Drug: Placebo administration
patients will receive the placebo treatment in addition to Standard of Care
Diagnostic Test: Confirm SARS-CoV-2 infection
patients will be tested for SARS-CoV-2 on days 1, 14 and 28
Other Name: Covid-19 test
Procedure: Physical Examination
patients will undergo a physical examination on days 1-14 and day 28
Procedure: Vital Signs
patient's vital signs will be measured on days 1-14 and day 28
Diagnostic Test: Hematology blood test
patients will provide a blood sample for a hematology blood test on days 1-14 and day 28
Other Name: blood tests
Diagnostic Test: Biochemistry blood test
patients will provide a blood sample for a biochemistry blood test on days 1-14 and day
28
Other Name: blood tests
Other: NEWS score
patient's NEWS score will be evaluated on days 1-14 and day 28
Other Name: scoring
Diagnostic Test: PK test
PK test will be performed on day 1 only (only in Brazil sites)
Other Name: pharmacokinetics
Diagnostic Test: blood 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
Other Name: blood tests
Diagnostic Test: D-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
Other Name: blood tests
Other: VAS scale
patient's VAS scale will be evaluated on days 1-14, day 21, and day 28
Other Name: scoring
Diagnostic Test: Urine pregnancy test for women of childbearing potential
patients will provide a urine sample for a urine pregnancy test on days 1, and day 28
Other Name: pregnancy test
Procedure: ECG
patients will undergo an ECG examination on days 1, and day 28
Other: COVID-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
Drug: CimetrA-1
patients will receive the study treatment, CimetrA-1 treatment in addition to Standard of
Care
Other Name: CimetrA-1 drug administration
Drug: CimetrA-2
patients will receive the study treatment, CimetrA-2 treatment in addition to Standard of
Care
Other Name: CimetrA- 2 drug administration
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.
Nazareth Hospital EMMS
Nazareth, North, Israel
Rambam Medical Center
Haifa, Israel
Not Provided