A Phase II, Controlled Clinical Study Designed to Evaluate the Effect of ArtemiC in Patients Diagnosed With COVID-19

• ClinicalTrials.gov Identifier: NCT04382040
• Recruitment Status: Completed
• First Posted: May 11, 2020
• Last Update Posted: March 3, 2021
• Sponsor: MGC Pharmaceuticals d.o.o
• Information provided by (Responsible Party): MGC Pharmaceuticals d.o.o

Tracking Information

• First Submitted Date: May 7, 2020
• First Posted Date: May 11, 2020
• Last Update Posted Date: March 3, 2021
• Actual Study Start Date: May 8, 2020
• Actual Primary Completion Date: November 5, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 7, 2020)

• Time to clinical improvement, defined as a national Early Warning Score 2 (NEWS2) of </= 2 Maintained for 24 Hours in comparison to routine treatment [ Time Frame: 24 hours ]
  patient will be assessed using a scoring table for changes in clinical signs
• Percentage of participants with definite or probable drug related adverse events [ Time Frame: 14 days ]
  Adverse events caused by the study drug will be assessed

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 7, 2020)

• Time to negative COVID-19 PCR [ Time Frame: 14 days ]
• Proportion of participants with normalization of fever and oxygen saturation through day 14 since onset of symptoms [ Time Frame: 14 days ]
• COVID-19 related survival [ Time Frame: 14 days ]
• Incidence and duration of mechanical ventilation [ Time Frame: 14 days ]
• Incidence of Intensive Care Init (ICU) stay [ Time Frame: 14 days ]
• Duration of ICU stay [ Time Frame: 14 days ]
• Duration of time on supplemental oxygen [ Time Frame: 14 days ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase II, Controlled Clinical Study Designed to Evaluate the Effect of ArtemiC in Patients Diagnosed With COVID-19
• Official Title: A Phase II, Controlled Clinical Study Designed to Evaluate the Effect of ArtemiC in Patients Diagnosed With COVID-19

Brief Summary

Agent Name and Study Duration

ArtemiC is a medical spray comprised of Artemisinin (6 mg/ml), Curcumin (20 mg/ml), Frankincense (=Boswellia) (15 mg/ml) and vitamin C (60 mg/ml) in micellar formulation for spray administration.

Patients will receive up to 6 mg Artemisinin, 20 mg Curcumin, 15 mg Frankincense and 60 mg vitamin C given daily as an add-on therapy (in addition to standard care) in two divided doses, on Days 1 and 2.

Patients will be randomized in a manner of 2:1 for study drug (ArteminC) and Standard of Care to Placebo and Standard of Care.

Patient follow-up will last 2 weeks. During this time, patients will be monitored for adverse events.

Additional time will be required for follow up (until hospital discharge) in order to check side effects and study drug efficacy.

Placebo, composed of the same solvent but without active ingredients, will be given in the placebo group as add-on therapy, 2 times a day, on Days 1 and 2.

Overall rationale A preparation of ArtemiC, comprising Artemisinin, 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. It is readily available in light of its status as a food supplement. 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.

Leading among these considerations are well established immuno-modulatory activities of the active ingredients as established in vitro and in vivo and published over the years. These activities as apparent, for example, in diminishing activity of TNF alpha and IL-6 levels are acknowledged to be relevant to the pathophysiology processes involved in the progressive form of COVID-19. The active agents have in addition prominent anti-oxidant, anti-inflammatory as well as anti-aggregant and anti-microbial activities.

Based on these activities and observations in animal models, together with clinical experience of the separate ingredients and in various combinations in other contexts it is proposed to evaluate their effect in the context of COVID-19.

Study Purpose This study is designed to evaluate the safety and efficacy of ArtemiC on patients diagnosed with COVID-19.

Methodology 50 adult patients who suffer from COVID-19 infection studied in parallel groups treated with active agent or placebo as add on to standard care.

Safety will be assessed through collection and analysis of adverse events, blood and urine laboratory assessments and vital signs.

Detailed Description

STUDY OBJECTIVES This study is designed to evaluate the safety and efficacy of ArtemiC on patients diagnosed with COVID-19.

STUDY TREATMENT AND DESIGN 50 adult patients who suffer from COVID-19 infection, and do not participant in any other clinical trial.

Patient must agree to not participate in any new clinical study during the study duration.

ArtemiC is a medical spray combined of Artemisinin (6 mg/ml), Curcumin (20 mg/ml), Frankincense (15 mg/ml) and vitamin C (60 mg/ml) in spray administration.

It has a current status as a food supplement. Patients will receive up to 12 mg Artemisinin, 40 mg Curcumin, 30 mg Frankincense and 120 mg vitamin C in 2ml as a total maximum dose, given as add-on therapy, comprised of 2 daily doses of 0.5 ml each, on Days 1 and 2. Each dose contains 0.5 ml (total 1 ml daily dose), which is equal to 5 pushes on the spray bottle.

Placebo, composed of the same solvent but without active ingredients, will be given as add-on therapy in the placebo group, 2 times a day, on Days 1 and 2.

Patients will be randomized in a manner of 2:1 for study drug (ArteminC) and Standard of Care to Placebo and Standard of Care.

The study will last 2 weeks. During this time, patients will be monitored for adverse events.

Additional time will be required for follow up (until hospital discharge) in order to check side effects and study drug efficacy.

STUDY PROCEDURES

Evaluation of the effect of oral administration of the study drug will be assessed by determining the clinical and laboratory tests as summarized below:

Biochemistry Blood Test: Sodium (Na), Potassium (K), Chloride (Cl), Creatinine, Glucose, Urea, Albumin, Calcium total, Alkaline Phosphatase (ALP), ALT, AST, Total Bilirubin, Direct Bilirubin, LDH, Total Protein, Uric Acid, CRP, and Lipid Profile (including Total Cholesterol, HDL, LDL, Triglycerides), D-dimer, ESR as well as Troponin as required.It will be performed per institutional schedule.

Hematology Blood Test: complete CBC. It will be performed per institutional schedule.

Vital signs: blood pressure, pulse, weight, height, temperature. It will be performed per institutional schedule.

Women of childbearing potential must undergo a urine pregnancy test. Physical examination: It will be performed per institutional schedule. All the above measurements will be performed by the hospital staff, not necessarily by the principal investigator or the sub-investigators.

Day 1 Prior to engaging in any study procedures, the subject must meet the inclusion/exclusion criteria by history (which includes a declination), and review and sign an ICF. Following procedures will be performed during the visit -

• Inclusion/Exclusion criteria evaluation
• ICF
• Medical history
• Concomitant medication
• Physical examination
• Vital signs
• Urine pregnancy test (if relevant)
• Test for detection of COVID-19
• Hematology blood test
• Biochemistry blood test
• Randomization (2:1 for study drug (ArteminC) and Standard of Care to Placebo and Standard of Care) and study drug administration

Day 2

• Concomitant medication
• Adverse Events assessment
• Physical examination
• Vital signs
• Hematology blood test
• Biochemistry blood test
• Study drug administration

Days 3-14

• Concomitant medication
• Adverse Events assessment
• Physical examination-is per institutional schedule
• Vital signs- is per institutional schedule
• Hematology blood test- is per institutional schedule
• Biochemistry blood test- is per institutional schedule

Follow up - Hospital Discharge

• Concomitant medication
• Adverse Events assessment
• Physical examination
• Vital signs
• Test for detection COVID-19
• Hematology blood test
• Biochemistry blood test

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Patients will be randomized in a manner of 2:1 for study drug (ArteminC) and Standard of Care to Placebo and Standard of Care.

Patient study period will last 2 weeks. During this time, patients will be monitored for adverse events.

There will be a follow up period (until hospital discharge) in order to check side effects and study drug efficacy

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition

• COVID-19
• Corona Virus Infection
• SARS-CoV 2
• Coronavirus
• Coronavirus Infection

Intervention

• Drug: ArtemiC
  Treatment will be sprayed orally twice a day for the first 2 days in the treatment period
• Drug: Placebo
  Treatment will be sprayed orally twice a day for the first 2 days in the treatment period

Study Arms

• Experimental: ArtemiC
  Active study treatment + Standard care
  Intervention: Drug: ArtemiC
• Placebo Comparator: PLACEBO
  Placebo + Standard care
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 7, 2020): 50
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 21, 2020
• Actual Primary Completion Date: November 5, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Confirmed SARS-CoV-2 infection.
2. Hospitalized COVID-19 patient in stable moderate condition (i.e., not requiring ICU admission).
3. Subjects must be under observation or admitted to a controlled facility or hospital (home quarantine is not sufficient).

Exclusion Criteria:

1. Tube feeding or parenteral nutrition.
2. Patients who are symptomatic and require oxygen (Ordinal Scale for Clinical Improvement score >3) at the time of screening.
3. Respiratory decompensation requiring mechanical ventilation.
4. Uncontrolled diabetes type 2.
5. Autoimmune disease.
6. Pregnant or lactating women.
7. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: India, Israel

Administrative Information

• NCT Number: NCT04382040
• Other Study ID Numbers: MGC-006
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: MGC Pharmaceuticals d.o.o
• Study Sponsor: MGC Pharmaceuticals d.o.o
• Collaborators: Not Provided

Investigators

• Study Director: Rubi Zomer; MGC Pharmaceuticals

• PRS Account: MGC Pharmaceuticals d.o.o
• Verification Date: May 2020