To Evaluate Safety and Efficacy of Nuvastatic as an Immunomodulator Adjuvant Therapy in COVID-19 Patients.

Study Overview
=================
Brief Summary
-----------------
A two arm open label multi-centered randomized interventional trial is proposed to assess aspects of safety and efficacy of Nuvastatic™ (Serial No: C5OSEW5050ESA) . Two parallel groups of (1:1) ratio comparing Nuvastatic™ versus standard care will be conducted on patients on oxygen saturation (SaO2) of 94% or less while they are breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) (PaO2:FiO2) at or below 300 mg Hg. Primary Outcome Measures: time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever comes first. Secondary Outcome Measures: Clinical status as assessed with the seven-category ordinal scale on days 7 and 14, mortality at day 28. The duration of mechanical ventilation. The duration of hospitalization in survivors. The time (in days) from treatment initiation to death. Virologic measures included the proportions with viral RNA detection over time and viral RNA titer area under-curve (auc) measurements.

Detailed Description
-----------------
This study will propose Nuvastiatic™ as a new lead therapeutic agent for SARS-CoV-2, and new insights for currently ongoing clinical trials to treat SARS-CoV-2 infections. Nuvastatic™ could be used as potential anti-coronavirus therapy that acts on the human immune system or human cells as an immune modulator, and the other on coronavirus itself as an antiviral agent. In terms of the human immune system, the innate immune system response plays an important role in controlling the replication and infection of coronavirus, and interferon gamma, interleukins, Th cells, granulocyte macrophage are expected to enhance the immune response.

Official Title
-----------------
An Open Label Proof of Concept Study to Assess Aspects of Safety and Efficacy of Nuvastatic™ (C5OSEW5050ESA) as an Immunomodulator Adjuvant Therapy to the Standard Care of Treatment in Covid 19 Patients.

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Drug: Nuvastatic


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and nonpregnant female patients 18 years of age or older eligible if they had a diagnostic specimen that was positive on RT-PCR. - For Mild - Moderate cases: Subjects who show positive for nasal swab test at screening using RT-PCR protocol for Covid 19. For Severe cases - Has an oxygen saturation (Sao2) of 94% or less while they are breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) (Pao2:Fio2) at or below 300 mg Hg. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Female subjects who are pregnant or breastfeeding. Patients who are allergic to this medicine Patients allergic to content of study product Patients with diabetes. Patients accompanied by serious physical diseases of heart, lung, brain, etc. Patients have any condition that in the judgement of the Investigators would make the subject inappropriate for entry into this study. Patients who are not able to take drugs orally.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Immunomodulator in COVID 19, Intervention - Sequentially numbered IP kits
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nuvastatic + standard treatment<br>5 patients, dosage: 3000 mg of Nuvastatic™ (C5OSEW5050ESA) each day plus standard of care thrice daily (morning, afternoon and evening (one sachet each) to be taken for 14 days in Covid-19 patients. | Drug: Nuvastatic<br>* Polymolecular botanical standardized extract Orthosiphon stamineus/Orthosiphon aristatas as an immunomodulator adjuvant therapy<br>* Other names: C5OSEW5050ESA;|
| Placebo Comparator: Placebo<br>5 patients, dosage: 3000 mg of placebo each day plus standard of care thrice daily (morning, afternoon and evening (one sachet each) to be taken for 14 days in Covid-19 patients. | Drug: Nuvastatic<br>* Polymolecular botanical standardized extract Orthosiphon stamineus/Orthosiphon aristatas as an immunomodulator adjuvant therapy<br>* Other names: C5OSEW5050ESA;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate safety and efficacy Nuvastatic™ (C5OSEW5050ESA) | Time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever comes first. | 14 Days | 
| IL-6 reduction | Improvement of Biomarkers: IL-6 reduction | 14 Days | 
| Serum c-reactive protein (CRP) | Improvement of Biomarkers:key inflammatory markers Serum c-reactive protein (CRP) | 14 Days | 
| IgG | Improvement of Biomarkers:key inflammatory markers IgG | 14 Days | 
| Hb | Improvement of Biomarkers:key inflammatory markers Hb | 14 Days | 
| Total leucocyte count | Improvement of Biomarkers:key inflammatory markers Total leucocyte count | 14 Days | 
| F2-Isoprostane | Improvement of Biomarkers:key inflammatory markers urinary F2-Isoprostane. | 14 Days | 
| Improvement in ARDS associated clinical symptoms cause | Role of VEGF as potential therapeutic target in acute respiratory distress syndrome (ARDS) | 14 Days |