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

M

MGC Pharmaceuticals

Status and phase

Active, not recruiting
Phase 3

Conditions

Corona Virus Infection
SARS-CoV Infection
Covid19

Treatments

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

Study type

Interventional

Funder types

Industry

Identifiers

NCT04802382
MGC-008

Details and patient eligibility

About

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).

Full 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)

Enrollment

252 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No 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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

252 participants in 3 patient groups, including a placebo group

Arm 1 - CimetrA-1
Experimental group
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).
Treatment:
Drug: CimetrA-1
Procedure: Vital Signs
Diagnostic Test: PK test
Other: NEWS score
Diagnostic Test: blood test for inflammatory markers
Diagnostic Test: Hematology blood test
Diagnostic Test: D-dimer test
Diagnostic Test: Confirm SARS-CoV-2 infection
Procedure: Physical Examination
Other: VAS scale
Other: COVID-19-Impact on Quality of Life Questionnaire
Diagnostic Test: Urine pregnancy test for women of childbearing potential
Diagnostic Test: Biochemistry blood test
Procedure: ECG
Arm 2 - CimetrA-2
Experimental group
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).
Treatment:
Procedure: Vital Signs
Diagnostic Test: PK test
Other: NEWS score
Diagnostic Test: blood test for inflammatory markers
Diagnostic Test: Hematology blood test
Diagnostic Test: D-dimer test
Diagnostic Test: Confirm SARS-CoV-2 infection
Procedure: Physical Examination
Other: VAS scale
Other: COVID-19-Impact on Quality of Life Questionnaire
Diagnostic Test: Urine pregnancy test for women of childbearing potential
Drug: CimetrA-2
Diagnostic Test: Biochemistry blood test
Procedure: ECG
Arm 3 - Placebo
Placebo Comparator group
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).
Treatment:
Procedure: Vital Signs
Diagnostic Test: PK test
Other: NEWS score
Diagnostic Test: blood test for inflammatory markers
Diagnostic Test: Hematology blood test
Diagnostic Test: D-dimer test
Diagnostic Test: Confirm SARS-CoV-2 infection
Procedure: Physical Examination
Other: VAS scale
Drug: Placebo administration
Other: COVID-19-Impact on Quality of Life Questionnaire
Diagnostic Test: Urine pregnancy test for women of childbearing potential
Diagnostic Test: Biochemistry blood test
Procedure: ECG

Trial contacts and locations

2

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Data sourced from clinicaltrials.gov

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