Clinical Study Designed to Evaluate the Effect of CimetrA in Patients Diagnosed With COVID-19
- Conditions
- Corona Virus InfectionCovid19SARS-CoV Infection
- Interventions
- Diagnostic Test: Confirm SARS-CoV-2 infectionDrug: Placebo administrationProcedure: Physical ExaminationProcedure: Vital SignsDiagnostic Test: Hematology blood testDiagnostic Test: Biochemistry blood testOther: NEWS scoreDiagnostic Test: PK testDiagnostic Test: blood test for inflammatory markersDiagnostic Test: D-dimer testOther: VAS scaleDiagnostic Test: Urine pregnancy test for women of childbearing potentialProcedure: ECGOther: COVID-19-Impact on Quality of Life Questionnaire
- Registration Number
- NCT04802382
- Lead Sponsor
- MGC Pharmaceuticals d.o.o
- 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)
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 252
- Confirmed SARS-CoV-2 infection (according to nationally authorized laboratory criteria)
- Hospitalized patient with COVID-19 of moderate stable or worsening severity not requiring ICU admission.
- Age: 18 years old and above.
- Subjects must be under observation or admitted to a controlled facility or hospital (home quarantine is not sufficient).
- Ability to receive treatment by spray into the oral cavity
- Tube feeding or parenteral nutrition.
- 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)
- Need for admission to ICU during the present hospitalization at any time prior to completion of the recruitment to the study.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 3 - Placebo Physical Examination composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 3 - Placebo Vital Signs composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 3 - Placebo Hematology blood test composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 3 - Placebo Biochemistry blood test composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 3 - Placebo NEWS score composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 3 - Placebo PK test composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 3 - Placebo blood test for inflammatory markers composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 3 - Placebo D-dimer test composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 3 - Placebo ECG composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 2 - CimetrA-2 PK test a total dose containing a combination of Artemisinin 8.4 mg, Curcumin 28 mg, Boswellia 21 mg, and Vitamin C 84 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 2 - CimetrA-2 blood test for inflammatory markers a total dose containing a combination of Artemisinin 8.4 mg, Curcumin 28 mg, Boswellia 21 mg, and Vitamin C 84 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 2 - CimetrA-2 D-dimer test a total dose containing a combination of Artemisinin 8.4 mg, Curcumin 28 mg, Boswellia 21 mg, and Vitamin C 84 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 3 - Placebo COVID-19-Impact on Quality of Life Questionnaire composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 1 - CimetrA-1 Confirm SARS-CoV-2 infection a total dose containing a combination of Artemisinin 12 mg, Curcumin 40 mg, Boswellia 30 mg, and Vitamin C 120 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 1 - CimetrA-1 Physical Examination a total dose containing a combination of Artemisinin 12 mg, Curcumin 40 mg, Boswellia 30 mg, and Vitamin C 120 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 1 - CimetrA-1 Vital Signs a total dose containing a combination of Artemisinin 12 mg, Curcumin 40 mg, Boswellia 30 mg, and Vitamin C 120 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 1 - CimetrA-1 Hematology blood test a total dose containing a combination of Artemisinin 12 mg, Curcumin 40 mg, Boswellia 30 mg, and Vitamin C 120 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 1 - CimetrA-1 PK test a total dose containing a combination of Artemisinin 12 mg, Curcumin 40 mg, Boswellia 30 mg, and Vitamin C 120 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 1 - CimetrA-1 Biochemistry blood test a total dose containing a combination of Artemisinin 12 mg, Curcumin 40 mg, Boswellia 30 mg, and Vitamin C 120 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 1 - CimetrA-1 NEWS score a total dose containing a combination of Artemisinin 12 mg, Curcumin 40 mg, Boswellia 30 mg, and Vitamin C 120 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 2 - CimetrA-2 VAS scale a total dose containing a combination of Artemisinin 8.4 mg, Curcumin 28 mg, Boswellia 21 mg, and Vitamin C 84 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 1 - CimetrA-1 blood test for inflammatory markers a total dose containing a combination of Artemisinin 12 mg, Curcumin 40 mg, Boswellia 30 mg, and Vitamin C 120 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 1 - CimetrA-1 D-dimer test a total dose containing a combination of Artemisinin 12 mg, Curcumin 40 mg, Boswellia 30 mg, and Vitamin C 120 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 2 - CimetrA-2 Urine pregnancy test for women of childbearing potential a total dose containing a combination of Artemisinin 8.4 mg, Curcumin 28 mg, Boswellia 21 mg, and Vitamin C 84 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 3 - Placebo VAS scale composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 2 - CimetrA-2 ECG a total dose containing a combination of Artemisinin 8.4 mg, Curcumin 28 mg, Boswellia 21 mg, and Vitamin C 84 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 2 - CimetrA-2 COVID-19-Impact on Quality of Life Questionnaire a total dose containing a combination of Artemisinin 8.4 mg, Curcumin 28 mg, Boswellia 21 mg, and Vitamin C 84 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 1 - CimetrA-1 VAS scale a total dose containing a combination of Artemisinin 12 mg, Curcumin 40 mg, Boswellia 30 mg, and Vitamin C 120 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 1 - CimetrA-1 COVID-19-Impact on Quality of Life Questionnaire a total dose containing a combination of Artemisinin 12 mg, Curcumin 40 mg, Boswellia 30 mg, and Vitamin C 120 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 2 - CimetrA-2 Confirm SARS-CoV-2 infection a total dose containing a combination of Artemisinin 8.4 mg, Curcumin 28 mg, Boswellia 21 mg, and Vitamin C 84 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 2 - CimetrA-2 CimetrA-2 a total dose containing a combination of Artemisinin 8.4 mg, Curcumin 28 mg, Boswellia 21 mg, and Vitamin C 84 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 3 - Placebo Placebo administration composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 3 - Placebo Confirm SARS-CoV-2 infection composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 1 - CimetrA-1 Urine pregnancy test for women of childbearing potential a total dose containing a combination of Artemisinin 12 mg, Curcumin 40 mg, Boswellia 30 mg, and Vitamin C 120 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 1 - CimetrA-1 ECG a total dose containing a combination of Artemisinin 12 mg, Curcumin 40 mg, Boswellia 30 mg, and Vitamin C 120 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 3 - Placebo Urine pregnancy test for women of childbearing potential composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 2 - CimetrA-2 Physical Examination a total dose containing a combination of Artemisinin 8.4 mg, Curcumin 28 mg, Boswellia 21 mg, and Vitamin C 84 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 2 - CimetrA-2 Vital Signs a total dose containing a combination of Artemisinin 8.4 mg, Curcumin 28 mg, Boswellia 21 mg, and Vitamin C 84 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 2 - CimetrA-2 Hematology blood test a total dose containing a combination of Artemisinin 8.4 mg, Curcumin 28 mg, Boswellia 21 mg, and Vitamin C 84 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 2 - CimetrA-2 Biochemistry blood test a total dose containing a combination of Artemisinin 8.4 mg, Curcumin 28 mg, Boswellia 21 mg, and Vitamin C 84 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 2 - CimetrA-2 NEWS score a total dose containing a combination of Artemisinin 8.4 mg, Curcumin 28 mg, Boswellia 21 mg, and Vitamin C 84 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening). Arm 1 - CimetrA-1 CimetrA-1 a total dose containing a combination of Artemisinin 12 mg, Curcumin 40 mg, Boswellia 30 mg, and Vitamin C 120 mg in spray administration - divided into 4 separate doses given as an add on therapy, 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Incidence of mechanical ventilation up to 28 days Incidence of mechanical ventilation
effective dose determination up to 28 days Definition of the active dose of CimetrA
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
Pharmacokinetic profile up to 28 days Pharmacokinetic profile of the study drug-Cmax (mmol/L)
oxygen dependency up to 28 days Number of participants with depending on oxygen supplementation through day 28 since onset of symptoms
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
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.
Trial Locations
- Locations (2)
Nazareth Hospital EMMS
🇮🇱Nazareth, North, Israel
Rambam Medical Center
🇮🇱Haifa, Israel