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

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ClinicalTrials.gov Identifier: NCT04802382
Recruitment Status : Not yet recruiting
First Posted : March 17, 2021
Last Update Posted : March 17, 2021
Sponsor:
Information provided by (Responsible Party):
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).


Condition or disease Intervention/treatment Phase
Corona Virus Infection Covid19 SARS-CoV Infection Drug: Placebo administration Diagnostic Test: Confirm SARS-CoV-2 infection Procedure: Physical Examination Procedure: Vital Signs Diagnostic Test: Hematology blood test Diagnostic Test: Biochemistry blood test Other: NEWS score Diagnostic Test: PK test Diagnostic Test: blood test for inflammatory markers Diagnostic Test: D-dimer test Other: VAS scale Diagnostic Test: Urine pregnancy test for women of childbearing potential Procedure: ECG Other: COVID-19-Impact on Quality of Life Questionnaire Drug: CimetrA-1 Drug: CimetrA-2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 252 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients will be randomized in 1:1:1 ratio to one of the three arms.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Double-blind , Controlled Clinical Study Designed to Evaluate the Effect of CimetrA in Patients Diagnosed With COVID-19
Estimated Study Start Date : April 2021
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 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).
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

Experimental: Arm 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).
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-2
patients will receive the study treatment, CimetrA-2 treatment in addition to Standard of Care
Other Name: CimetrA- 2 drug administration

Placebo Comparator: Arm 3 - Placebo
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).
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




Primary Outcome Measures :
  1. clinical improvement in treatment groups [ Time Frame: 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 :
  1. oxygen dependency [ Time Frame: up to 28 days ]
    Number of participants with depending on oxygen supplementation through day 28 since onset of symptoms

  2. change in inflammatory marker levels [ Time Frame: 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

  3. effective dose determination [ Time Frame: up to 28 days ]
    Definition of the active dose of CimetrA

  4. Pharmacokinetic profile [ Time Frame: up to 28 days ]
    Pharmacokinetic profile of the study drug-AUC(mmol/L·h)

  5. Pharmacokinetic profile [ Time Frame: up to 28 days ]
    Pharmacokinetic profile of the study drug-Tmax (Hour)

  6. Pharmacokinetic profile [ Time Frame: up to 28 days ]
    Pharmacokinetic profile of the study drug-Cmax (mmol/L)

  7. Incidence of mechanical ventilation [ Time Frame: up to 28 days ]
    Incidence of mechanical ventilation

  8. Incidence of Intensive Care Unit (ICU) stay during COVID-19 complication [ Time Frame: up to 28 days ]
    Incidence of Intensive Care Unit (ICU) stay during COVID-19 complication

  9. evaluation of drug related adverse events [ Time Frame: up to 28 days ]
    Percentage of participants with definite or probable drug related adverse events

  10. Long term adverse events of COVID-19 [ Time Frame: up to 28 days ]
    Long term adverse events of COVID-19 on Day 28

  11. Quality of life of patients [ Time Frame: 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.



Other Outcome Measures:
  1. Duration of mechanical ventilation [ Time Frame: up to day 28 ]
    Duration of mechanical ventilation

  2. Course of change in D Dimer levels compared to baseline [ Time Frame: up to 28 days ]
  3. Occurrence of secondary infections [ Time Frame: up to 28 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
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Responsible Party: MGC Pharmaceuticals d.o.o
ClinicalTrials.gov Identifier: NCT04802382    
Other Study ID Numbers: MGC-008
First Posted: March 17, 2021    Key Record Dates
Last Update Posted: March 17, 2021
Last Verified: March 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MGC Pharmaceuticals d.o.o:
corona
covid19
covid
coronavirus
corona virus infection
sars-cov-2
Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Communicable Diseases
Virus Diseases
Coronavirus Infections
Severe Acute Respiratory Syndrome
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Respiratory Tract Infections
Respiratory Tract Diseases
Fibrin fragment D
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants