Clinical trial NCT04802382: Clinical Study Designed to Evaluate the Effect of CimetrA in Patients Diagnosed With COVID-19
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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Corona Virus Infection
Covid19
SARS-CoV Infection
Keywords: corona
covid19
covid
coronavirus
corona virus infection
sars-cov-2
Lead sponsor: MGC Pharmaceuticals d.o.o
Sponsor class: INDUSTRY
First posted: 2021-03-17
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized in 1:1:1 ratio to one of the three arms.
Primary purpose: TREATMENT

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)

Eligibility 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.

Primary outcomes:
measure: clinical improvement in treatment groups
timeFrame: up to 28 days
Secondary outcomes:
measure: oxygen dependency
timeFrame: up to 28 days
measure: change in inflammatory marker levels
timeFrame: up to day 28
measure: effective dose determination
timeFrame: up to 28 days
measure: Pharmacokinetic profile
timeFrame: up to 28 days
measure: Pharmacokinetic profile
timeFrame: up to 28 days
measure: Pharmacokinetic profile
timeFrame: up to 28 days
measure: Incidence of mechanical ventilation
timeFrame: up to 28 days
measure: Incidence of Intensive Care Unit (ICU) stay during COVID-19 complication
timeFrame: up to 28 days
measure: evaluation of drug related adverse events
timeFrame: up to 28 days
measure: Long term adverse events of COVID-19
timeFrame: up to 28 days
measure: Quality of life of patients
timeFrame: up to 28 days
Other outcomes:
measure: Duration of mechanical ventilation
timeFrame: up to day 28
measure: Course of change in D Dimer levels compared to baseline
timeFrame: up to 28 days
measure: Occurrence of secondary infections
timeFrame: up to 28 days
Locations:
city: Nazareth
country: Israel
facility: Nazareth Hospital EMMS
state: North
city: Haifa
country: Israel
facility: Rambam Medical Center
Study officials:
References: