A Phase III, Double-blind , Controlled Clinical Study Designed to Evaluate the Effect of CimetrA in Patients Diagnosed With COVID-19
试验速览
- 阶段
- 3 期
- 入组人数
- 252
- 试验地点
- 2
- 主要终点
- clinical improvement in treatment groups
研究概览
简要总结
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).
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Arm 1 - CimetrA-1
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).
干预措施: NEWS score (Other)
Arm 1 - CimetrA-1
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).
干预措施: Biochemistry blood test (Diagnostic Test)
Arm 1 - CimetrA-1
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).
干预措施: Confirm SARS-CoV-2 infection (Diagnostic Test)
Arm 1 - CimetrA-1
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).
干预措施: Physical Examination (Procedure)
Arm 1 - CimetrA-1
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).
干预措施: Vital Signs (Procedure)
Arm 1 - CimetrA-1
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).
干预措施: Hematology blood test (Diagnostic Test)
Arm 1 - CimetrA-1
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).
干预措施: PK test (Diagnostic Test)
Arm 1 - CimetrA-1
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).
干预措施: blood test for inflammatory markers (Diagnostic Test)
Arm 1 - CimetrA-1
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).
干预措施: D-dimer test (Diagnostic Test)
Arm 1 - CimetrA-1
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).
干预措施: VAS scale (Other)
Arm 1 - CimetrA-1
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).
干预措施: Urine pregnancy test for women of childbearing potential (Diagnostic Test)
Arm 1 - CimetrA-1
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).
干预措施: ECG (Procedure)
Arm 1 - CimetrA-1
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).
干预措施: COVID-19-Impact on Quality of Life Questionnaire (Other)
Arm 1 - CimetrA-1
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).
干预措施: CimetrA-1 (Drug)
Arm 2 - CimetrA-2
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).
干预措施: Confirm SARS-CoV-2 infection (Diagnostic Test)
Arm 2 - CimetrA-2
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).
干预措施: Physical Examination (Procedure)
Arm 2 - CimetrA-2
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).
干预措施: Vital Signs (Procedure)
Arm 2 - CimetrA-2
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).
干预措施: Hematology blood test (Diagnostic Test)
Arm 2 - CimetrA-2
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).
干预措施: Biochemistry blood test (Diagnostic Test)
Arm 2 - CimetrA-2
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).
干预措施: NEWS score (Other)
Arm 2 - CimetrA-2
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).
干预措施: PK test (Diagnostic Test)
Arm 2 - CimetrA-2
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).
干预措施: blood test for inflammatory markers (Diagnostic Test)
Arm 3 - Placebo
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).
干预措施: Placebo administration (Drug)
Arm 2 - CimetrA-2
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).
干预措施: D-dimer test (Diagnostic Test)
Arm 2 - CimetrA-2
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).
干预措施: VAS scale (Other)
Arm 2 - CimetrA-2
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).
干预措施: Urine pregnancy test for women of childbearing potential (Diagnostic Test)
Arm 2 - CimetrA-2
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).
干预措施: ECG (Procedure)
Arm 2 - CimetrA-2
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).
干预措施: COVID-19-Impact on Quality of Life Questionnaire (Other)
Arm 2 - CimetrA-2
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).
干预措施: CimetrA-2 (Drug)
Arm 3 - Placebo
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).
干预措施: Confirm SARS-CoV-2 infection (Diagnostic Test)
Arm 3 - Placebo
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).
干预措施: Physical Examination (Procedure)
Arm 3 - Placebo
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).
干预措施: Vital Signs (Procedure)
Arm 3 - Placebo
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).
干预措施: Hematology blood test (Diagnostic Test)
Arm 3 - Placebo
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).
干预措施: Biochemistry blood test (Diagnostic Test)
Arm 3 - Placebo
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).
干预措施: NEWS score (Other)
Arm 3 - Placebo
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).
干预措施: PK test (Diagnostic Test)
Arm 3 - Placebo
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).
干预措施: blood test for inflammatory markers (Diagnostic Test)
Arm 3 - Placebo
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).
干预措施: D-dimer test (Diagnostic Test)
Arm 3 - Placebo
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).
干预措施: VAS scale (Other)
Arm 3 - Placebo
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).
干预措施: Urine pregnancy test for women of childbearing potential (Diagnostic Test)
Arm 3 - Placebo
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).
干预措施: ECG (Procedure)
Arm 3 - Placebo
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).
干预措施: COVID-19-Impact on Quality of Life Questionnaire (Other)
结局指标
主要结局
clinical improvement in treatment groups
时间窗: up to 28 days
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)
次要结局
- effective dose determination(up to 28 days)
- change in inflammatory marker levels(up to day 28)
- Pharmacokinetic profile(up to 28 days)
- Incidence of mechanical ventilation(up to 28 days)
- oxygen dependency(up to 28 days)
- Incidence of Intensive Care Unit (ICU) stay during COVID-19 complication(up to 28 days)
- evaluation of drug related adverse events(up to 28 days)
- Long term adverse events of COVID-19(up to 28 days)
- Quality of life of patients(up to 28 days)