Clinical trial NCT05037162: Study Designed to Evaluate the Effect of CimetrA in Patients Diagnosed With COVID-19
Official title: A Phase IIb, Double Blind, Placebo-controlled Clinical Study Designed to Evaluate the Effect of CimetrA in Patients Diagnosed With COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Corona Virus Infection
Keywords: Corona
covid19
COVID-19
coronavirus
corona virus infection
sars-cov-2
Lead sponsor: MGC Pharmaceuticals d.o.o
Sponsor class: INDUSTRY
First posted: 2021-09-08
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center multinational-controlled study in Israel, Brazil, Spain, and South-Africa.

240 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 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 two dosages in addition to Standard of Care - Arm 1, 2 or (Placebo) in addition to Standard of Care- Arm 3.
Primary purpose: TREATMENT

Brief summary: Multi-center multinational-controlled study in Israel, Brazil, Spain, and South-Africa.

240 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 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 two dosages in addition to Standard of Care - Arm 1, 2 or (Placebo) in addition to Standard of Care- Arm 3.

Detailed description: A preparation of CimertA (Botanical Drug), comprising Curcumin, Boswellia, and Vitamin C in a nanoparticular formulation, is proposed as a treatment for the disease associated with the novel corona virus 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 breakout of a lethal pneumonia in the city of Wuhan, China, towards the end of 2019, has led to the characterization of the new coronavirus related disease COVID-19. Its prominent features include a high rate of person-to-person transmission, a substantial risk of developing a lethal respiratory syndrome and potential failure of additional organs. Risk factors for a life-threatening clinical course have been identified, including advanced age and assorted comorbidities, such as cardiovascular disease, diabetes mellitus, hypertension, cancer. However, individuals devoid of any of the recognized risk factors are not immune to the severe manifestation of the disease and once infected carry a certain risk of mortality which has been calculated in Italy at circa 2%.

CoV is an enveloped, positive-sense single-stranded RNA (ss-RNA) virus belonging to the Coronaviridae family. The severe acute respiratory syndrome associated coronavirus disease 2019 (COVID-19) illness is a syndrome of viral replication in concert with a host inflammatory response. The cytokine storm and viral evasion of cellular immune responses may play an equally important role in the pathogenesis, clinical manifestation, and outcomes of COVID-19. Systemic proinflammatory cytokines and biomarkers are elevated as the disease progresses towards its advanced stages, and correlate with worse chances of survival.

SARS-CoV-2 activates the innate immune system and results in a release of a large number of cytokines, including IL-6, which can increase vascular permeability and cause a migration of fluid and blood cells into the alveoli as well as the consequent symptoms such as dyspnea and respiratory failure. The higher mortality is being linked to the result of ARDS (acute respiratory distress syndrome) aggravation and the tissue damage that can result in organ-failure and/or death.

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 plasma blasts 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, as they are in cytokine storm disorders. Laboratory test results reflecting hyperinflammation and tissue damage were found to predict worsening outcomes in Covid-19.

CimetrA, comprising Curcumin, Boswellia, and Vitamin C in a nanoparticular formulation, was studied on patients with the novel corona virus SARS-CoV-2 in randomized double blind control Phase II study (MGC-006 - under a previous product name - ArtemiC). The study product demonstrated excellent safety and efficacy profiles.

In the in vitro clinical trial CimetrA demonstrated the ability to reduce cytokines elevation in PBMC induced cell tissue.

Eligibility criteria: Inclusion Criteria:

1. Confirmed by PCR test 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 (defined by NIH criteria - fever, cough, dyspnea, fast breathing, but no signs of severe pneumonia, including SpO2 ≥ 94% on room air).
3. Age: 18 years old and above.
4. Subjects must be hospitalized
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: Change in WHO Ordinal Scale for clinical improvement
timeFrame: up to 28 days
measure: Change in COVID-19-Related Symptoms score
timeFrame: up to 28 days
measure: Safety endpoint: will be assessed through collection and analysis of adverse events
timeFrame: up to 28 days
measure: Safety endpoint: will be assessed through collection and analysis of blood laboratory test.
timeFrame: up to 28 days
measure: Safety endpoint: will be assessed through collection and analysis of urine laboratory test.
timeFrame: up to 28 days
measure: Safety endpoint: will be assessed through collection and analysis of blood preasure
timeFrame: up to 28 days
measure: Safety endpoint: will be assessed through collection and analysis of blood satturation
timeFrame: up to 28 days
measure: Safety endpoint: will be assessed through collection and analysis of body temperature
timeFrame: up to 28 days
Secondary outcomes:
measure: Number of participants with depending on oxygen supplementation through day 28 since onset of symptoms
timeFrame: up to 28 days
measure: 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, compared to baseline
timeFrame: up to 7 days
measure: Pharmacokinetic profile of the study drug
timeFrame: on day 1 through 24 Hrs
measure: Pharmacokinetic profile of the study drug - maximal concentartion
timeFrame: on day 1 through 24 Hrs
measure: Pharmacokinetic profile of the study drug - elimination rate constant (denoted as K)
timeFrame: on day 1 through 24 Hrs
measure: Pharmacokinetic profile of the study drug - half-life
timeFrame: on day 1 through 24 Hrs
measure: Pharmacokinetic profile of the study drug - apparent volume of distribution
timeFrame: on day 1 through 24 Hrs
measure: Pharmacokinetic profile of the study drug - total clearance rate
timeFrame: on day 1 through 24 Hrs
measure: Pharmacokinetic profile of the study drug - AUC
timeFrame: on day 1 through 24 Hrs
measure: duration 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: Percentage of participants with definite or probable drug related adverse events
timeFrame: up to 28 days
measure: Long term adverse events of COVID-19 on Day 28
timeFrame: up to 28 days
measure: The Impact covid_19 on Quality of life of patients on Days 1, 14 and 28.
timeFrame: up to 28 days
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
measure: Incidence of mechanical ventilation
timeFrame: up to 28 days
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: Rambam Medical Center
Study officials:
affiliation: Galilee CBR - CRO
name: Rita Nadaf
role: STUDY_DIRECTOR
References: