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Clinical Study Designed to Evaluate the Effect of CimetrA in Patients Diagnosed With COVID-19 (CimetrA)

Primary Purpose

Corona Virus Infection, Covid19, SARS-CoV Infection

Status
Active
Phase
Phase 3
Locations
Israel
Study Type
Interventional
Intervention
Placebo administration
Confirm SARS-CoV-2 infection
Physical Examination
Vital Signs
Hematology blood test
Biochemistry blood test
NEWS score
PK test
blood test for inflammatory markers
D-dimer test
VAS scale
Urine pregnancy test for women of childbearing potential
ECG
COVID-19-Impact on Quality of Life Questionnaire
CimetrA-1
CimetrA-2
Sponsored by
MGC Pharmaceuticals d.o.o
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Corona Virus Infection focused on measuring corona, covid19, covid, coronavirus, corona virus infection, sars-cov-2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Nazareth Hospital EMMS
  • Rambam Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Arm 1 - CimetrA-1

Arm 2 - CimetrA-2

Arm 3 - Placebo

Arm Description

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).

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).

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).

Outcomes

Primary Outcome Measures

clinical improvement in treatment groups
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

oxygen dependency
Number of participants with depending on oxygen supplementation through day 28 since onset of symptoms
change in inflammatory marker levels
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
Definition of the active dose of CimetrA
Pharmacokinetic profile
Pharmacokinetic profile of the study drug-AUC(mmol/L·h)
Pharmacokinetic profile
Pharmacokinetic profile of the study drug-Tmax (Hour)
Pharmacokinetic profile
Pharmacokinetic profile of the study drug-Cmax (mmol/L)
Incidence of mechanical ventilation
Incidence of mechanical ventilation
Incidence of Intensive Care Unit (ICU) stay during COVID-19 complication
Incidence of Intensive Care Unit (ICU) stay during COVID-19 complication
evaluation of drug related adverse events
Percentage of participants with definite or probable drug related adverse events
Long term adverse events of COVID-19
Long term adverse events of COVID-19 on Day 28
Quality of life of patients
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.

Full Information

First Posted
March 10, 2021
Last Updated
August 23, 2022
Sponsor
MGC Pharmaceuticals d.o.o
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1. Study Identification

Unique Protocol Identification Number
NCT04802382
Brief Title
Clinical Study Designed to Evaluate the Effect of CimetrA in Patients Diagnosed With COVID-19
Acronym
CimetrA
Official Title
A Phase III, Double-blind , Controlled Clinical Study Designed to Evaluate the Effect of CimetrA in Patients Diagnosed With COVID-19
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 11, 2021 (Actual)
Primary Completion Date
February 2023 (Anticipated)
Study Completion Date
April 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MGC Pharmaceuticals d.o.o

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corona Virus Infection, Covid19, SARS-CoV Infection
Keywords
corona, covid19, covid, coronavirus, corona virus infection, sars-cov-2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Patients will be randomized in 1:1:1 ratio to one of the three arms.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
252 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1 - CimetrA-1
Arm Type
Experimental
Arm Description
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 Title
Arm 2 - CimetrA-2
Arm Type
Experimental
Arm Description
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 Title
Arm 3 - Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Placebo administration
Intervention Description
patients will receive the placebo treatment in addition to Standard of Care
Intervention Type
Diagnostic Test
Intervention Name(s)
Confirm SARS-CoV-2 infection
Other Intervention Name(s)
Covid-19 test
Intervention Description
patients will be tested for SARS-CoV-2 on days 1, 14 and 28
Intervention Type
Procedure
Intervention Name(s)
Physical Examination
Intervention Description
patients will undergo a physical examination on days 1-14 and day 28
Intervention Type
Procedure
Intervention Name(s)
Vital Signs
Intervention Description
patient's vital signs will be measured on days 1-14 and day 28
Intervention Type
Diagnostic Test
Intervention Name(s)
Hematology blood test
Other Intervention Name(s)
blood tests
Intervention Description
patients will provide a blood sample for a hematology blood test on days 1-14 and day 28
Intervention Type
Diagnostic Test
Intervention Name(s)
Biochemistry blood test
Other Intervention Name(s)
blood tests
Intervention Description
patients will provide a blood sample for a biochemistry blood test on days 1-14 and day 28
Intervention Type
Other
Intervention Name(s)
NEWS score
Other Intervention Name(s)
scoring
Intervention Description
patient's NEWS score will be evaluated on days 1-14 and day 28
Intervention Type
Diagnostic Test
Intervention Name(s)
PK test
Other Intervention Name(s)
pharmacokinetics
Intervention Description
PK test will be performed on day 1 only (only in Brazil sites)
Intervention Type
Diagnostic Test
Intervention Name(s)
blood test for inflammatory markers
Other Intervention Name(s)
blood tests
Intervention Description
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
Intervention Type
Diagnostic Test
Intervention Name(s)
D-dimer test
Other Intervention Name(s)
blood tests
Intervention Description
patients will provide a blood sample for D-dimer blood test on days 1, day 2, day 7, day 14, and day 28
Intervention Type
Other
Intervention Name(s)
VAS scale
Other Intervention Name(s)
scoring
Intervention Description
patient's VAS scale will be evaluated on days 1-14, day 21, and day 28
Intervention Type
Diagnostic Test
Intervention Name(s)
Urine pregnancy test for women of childbearing potential
Other Intervention Name(s)
pregnancy test
Intervention Description
patients will provide a urine sample for a urine pregnancy test on days 1, and day 28
Intervention Type
Procedure
Intervention Name(s)
ECG
Intervention Description
patients will undergo an ECG examination on days 1, and day 28
Intervention Type
Other
Intervention Name(s)
COVID-19-Impact on Quality of Life Questionnaire
Intervention Description
patients will answer the COVID-19-Impact on Quality of Life Questionnaire on days 1, 7,14,21 and 28
Intervention Type
Drug
Intervention Name(s)
CimetrA-1
Other Intervention Name(s)
CimetrA-1 drug administration
Intervention Description
patients will receive the study treatment, CimetrA-1 treatment in addition to Standard of Care
Intervention Type
Drug
Intervention Name(s)
CimetrA-2
Other Intervention Name(s)
CimetrA- 2 drug administration
Intervention Description
patients will receive the study treatment, CimetrA-2 treatment in addition to Standard of Care
Primary Outcome Measure Information:
Title
clinical improvement in treatment groups
Description
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)
Time Frame
up to 28 days
Secondary Outcome Measure Information:
Title
oxygen dependency
Description
Number of participants with depending on oxygen supplementation through day 28 since onset of symptoms
Time Frame
up to 28 days
Title
change in inflammatory marker levels
Description
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
Time Frame
up to day 28
Title
effective dose determination
Description
Definition of the active dose of CimetrA
Time Frame
up to 28 days
Title
Pharmacokinetic profile
Description
Pharmacokinetic profile of the study drug-AUC(mmol/L·h)
Time Frame
up to 28 days
Title
Pharmacokinetic profile
Description
Pharmacokinetic profile of the study drug-Tmax (Hour)
Time Frame
up to 28 days
Title
Pharmacokinetic profile
Description
Pharmacokinetic profile of the study drug-Cmax (mmol/L)
Time Frame
up to 28 days
Title
Incidence of mechanical ventilation
Description
Incidence of mechanical ventilation
Time Frame
up to 28 days
Title
Incidence of Intensive Care Unit (ICU) stay during COVID-19 complication
Description
Incidence of Intensive Care Unit (ICU) stay during COVID-19 complication
Time Frame
up to 28 days
Title
evaluation of drug related adverse events
Description
Percentage of participants with definite or probable drug related adverse events
Time Frame
up to 28 days
Title
Long term adverse events of COVID-19
Description
Long term adverse events of COVID-19 on Day 28
Time Frame
up to 28 days
Title
Quality of life of patients
Description
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.
Time Frame
up to 28 days
Other Pre-specified Outcome Measures:
Title
Duration of mechanical ventilation
Description
Duration of mechanical ventilation
Time Frame
up to day 28
Title
Course of change in D Dimer levels compared to baseline
Time Frame
up to 28 days
Title
Occurrence of secondary infections
Time Frame
up to 28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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.
Facility Information:
Facility Name
Nazareth Hospital EMMS
City
Nazareth
State/Province
North
Country
Israel
Facility Name
Rambam Medical Center
City
Haifa
Country
Israel

12. IPD Sharing Statement

Learn more about this trial

Clinical Study Designed to Evaluate the Effect of CimetrA in Patients Diagnosed With COVID-19

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