NCT04802382

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).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
252

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jun 2021

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 10, 2021

Completed
7 days until next milestone

First Posted

Study publicly available on registry

March 17, 2021

Completed
3 months until next milestone

Study Start

First participant enrolled

June 11, 2021

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2023

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2023

Completed
Last Updated

August 24, 2022

Status Verified

August 1, 2022

Enrollment Period

1.6 years

First QC Date

March 10, 2021

Last Update Submit

August 23, 2022

Conditions

Keywords

coronacovid19covidcoronaviruscorona virus infectionsars-cov-2

Outcome Measures

Primary Outcomes (1)

  • 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)

    up to 28 days

Secondary Outcomes (11)

  • oxygen dependency

    up to 28 days

  • change in inflammatory marker levels

    up to day 28

  • effective dose determination

    up to 28 days

  • Pharmacokinetic profile

    up to 28 days

  • Pharmacokinetic profile

    up to 28 days

  • +6 more secondary outcomes

Other Outcomes (3)

  • Duration of mechanical ventilation

    up to day 28

  • Course of change in D Dimer levels compared to baseline

    up to 28 days

  • Occurrence of secondary infections

    up to 28 days

Study Arms (3)

Arm 1 - CimetrA-1

EXPERIMENTAL

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 infectionProcedure: 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 QuestionnaireDrug: CimetrA-1

Arm 2 - CimetrA-2

EXPERIMENTAL

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 infectionProcedure: 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 QuestionnaireDrug: CimetrA-2

Arm 3 - Placebo

PLACEBO COMPARATOR

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 administrationDiagnostic Test: Confirm SARS-CoV-2 infectionProcedure: 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

Interventions

patients will receive the placebo treatment in addition to Standard of Care

Arm 3 - Placebo

patients will be tested for SARS-CoV-2 on days 1, 14 and 28

Also known as: Covid-19 test
Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo

patients will undergo a physical examination on days 1-14 and day 28

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
Vital SignsPROCEDURE

patient's vital signs will be measured on days 1-14 and day 28

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
Hematology blood testDIAGNOSTIC_TEST

patients will provide a blood sample for a hematology blood test on days 1-14 and day 28

Also known as: blood tests
Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo

patients will provide a blood sample for a biochemistry blood test on days 1-14 and day 28

Also known as: blood tests
Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo

patient's NEWS score will be evaluated on days 1-14 and day 28

Also known as: scoring
Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
PK testDIAGNOSTIC_TEST

PK test will be performed on day 1 only (only in Brazil sites)

Also known as: pharmacokinetics
Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo

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

Also known as: blood tests
Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
D-dimer testDIAGNOSTIC_TEST

patients will provide a blood sample for D-dimer blood test on days 1, day 2, day 7, day 14, and day 28

Also known as: blood tests
Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo

patient's VAS scale will be evaluated on days 1-14, day 21, and day 28

Also known as: scoring
Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo

patients will provide a urine sample for a urine pregnancy test on days 1, and day 28

Also known as: pregnancy test
Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
ECGPROCEDURE

patients will undergo an ECG examination on days 1, and day 28

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo

patients will answer the COVID-19-Impact on Quality of Life Questionnaire on days 1, 7,14,21 and 28

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo

patients will receive the study treatment, CimetrA-1 treatment in addition to Standard of Care

Also known as: CimetrA-1 drug administration
Arm 1 - CimetrA-1

patients will receive the study treatment, CimetrA-2 treatment in addition to Standard of Care

Also known as: CimetrA- 2 drug administration
Arm 2 - CimetrA-2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Nazareth Hospital EMMS

Nazareth, North, Israel

Location

Rambam Medical Center

Haifa, Israel

Location

MeSH Terms

Conditions

Coronavirus InfectionsCOVID-19Severe Acute Respiratory Syndrome

Interventions

Restraint, PhysicalHematologic TestsPharmacokineticsPregnancy Tests

Condition Hierarchy (Ancestors)

Coronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsVirus DiseasesInfectionsPneumonia, ViralPneumoniaRespiratory Tract InfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Behavior ControlTherapeuticsImmobilizationInvestigative TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisMetabolismPharmacological and Toxicological PhenomenaPhysiological PhenomenaDiagnostic Techniques, Obstetrical and Gynecological

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Patients will be randomized in 1:1:1 ratio to one of the three arms.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 10, 2021

First Posted

March 17, 2021

Study Start

June 11, 2021

Primary Completion

February 1, 2023

Study Completion

April 1, 2023

Last Updated

August 24, 2022

Record last verified: 2022-08

Locations