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

Covid19 Clinical Trial

— CimetrA  

Official title:

A Phase III, Double-blind , Controlled Clinical Study Designed to Evaluate the Effect of CimetrA in Patients Diagnosed With COVID-19

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04802382
• Other study ID #: MGC-008
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 11, 2021
• Est. completion date: April 2023

Study information

• Verified date: August 2022
• Source: MGC Pharmaceuticals d.o.o
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 252
• Est. completion date: April 2023
• Est. primary completion date: February 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Corona Virus Infection
• Coronavirus Infections
• COVID-19
• Covid19
• Infections
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome
• Virus Diseases

Intervention

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

Procedure:
• Physical Examination
patients will undergo a physical examination on days 1-14 and day 28
• 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
• Biochemistry blood test
patients will provide a blood sample for a biochemistry blood test on days 1-14 and day 28

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

Diagnostic Test:
• PK test
PK test will be performed on day 1 only (only in Brazil sites)
• blood test for inflammatory markers
patients will provide a blood sample for an inflammatory markers blood test (IL-6, IL-1ß, IL-12, TNF a, IFN-?) on days 1-7, day 14, and day 28
• 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:
• VAS scale
patient's VAS scale will be evaluated on days 1-14, day 21, and day 28

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

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

Locations

Country	Name	City	State
Israel	Rambam Medical Center	Haifa
Israel	Nazareth Hospital EMMS	Nazareth	North

Sponsors (1)

Lead Sponsor	Collaborator
MGC Pharmaceuticals d.o.o

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Duration of mechanical ventilation	Duration of mechanical ventilation	up to day 28
Other	Course of change in D Dimer levels compared to baseline		up to 28 days
Other	Occurrence of secondary infections		up to 28 days
Primary	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	oxygen dependency	Number of participants with depending on oxygen supplementation through day 28 since onset of symptoms	up to 28 days
Secondary	change in inflammatory marker levels	Change in inflammatory marker levels - IL-6, IL-1ß, IL-12, TNF a, IFN-?, CRP, NLR (Neutrophil / Lymphocyte ratio) at days 1, 2, 4, 7, 14, 28	up to day 28
Secondary	effective dose determination	Definition of the active dose of CimetrA	up to 28 days
Secondary	Pharmacokinetic profile	Pharmacokinetic profile of the study drug-AUC(mmol/L·h)	up to 28 days
Secondary	Pharmacokinetic profile	Pharmacokinetic profile of the study drug-Tmax (Hour)	up to 28 days
Secondary	Pharmacokinetic profile	Pharmacokinetic profile of the study drug-Cmax (mmol/L)	up to 28 days
Secondary	Incidence of mechanical ventilation	Incidence of mechanical ventilation	up to 28 days
Secondary	Incidence of Intensive Care Unit (ICU) stay during COVID-19 complication	Incidence of Intensive Care Unit (ICU) stay during COVID-19 complication	up to 28 days
Secondary	evaluation of drug related adverse events	Percentage of participants with definite or probable drug related adverse events	up to 28 days
Secondary	Long term adverse events of COVID-19	Long term adverse events of COVID-19 on Day 28	up to 28 days
Secondary	Quality of life of patients	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.	up to 28 days