NCT05037162

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
240

participants targeted

Target at P50-P75 for phase_2 covid19

Timeline
Completed

Started Oct 2022

Shorter than P25 for phase_2 covid19

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 15, 2021

Completed
24 days until next milestone

First Posted

Study publicly available on registry

September 8, 2021

Completed
1.1 years until next milestone

Study Start

First participant enrolled

October 11, 2022

Completed
3 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 21, 2023

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2023

Completed
Last Updated

March 15, 2023

Status Verified

March 1, 2023

Enrollment Period

3 months

First QC Date

August 15, 2021

Last Update Submit

March 14, 2023

Conditions

Covid19Corona Virus Infection

Keywords

Coronacovid19COVID-19coronaviruscorona virus infectionsars-cov-2

Outcome Measures

Primary Outcomes (8)

  • Change in WHO Ordinal Scale for clinical improvement

    measured on days 1, 7, 14, 28 numerical value to assess the health status of the participant , scale is between 0-8 , The higher score means the worse outcome .

    up to 28 days

  • Change in COVID-19-Related Symptoms score

    measured on days 1,7, 14, 28 numerical value to assess the COVID-19-Related symptoms of participant scale is between 0-3, The higher score means the worse outcome . score 0-3; higher score indicates worse outcome.

    up to 28 days

  • Safety endpoint: will be assessed through collection and analysis of adverse events

    Data management team will assess and review the AE's and SAE'S.

    up to 28 days

  • Safety endpoint: will be assessed through collection and analysis of blood laboratory test.

    Data management team will assess and review the lab test results (blood), assessment will be compared to the normal range. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition

    up to 28 days

  • Safety endpoint: will be assessed through collection and analysis of urine laboratory test.

    Data management team will assess and review the lab test results (urine), assessment will be compared to the normal range. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition

    up to 28 days

  • Safety endpoint: will be assessed through collection and analysis of blood preasure

    units: BPM (beats per minute) Data management team will assess and review the vital signs : blood pressure \[mm Hg\], saturation \[%\], body temperature \[C\] , Each category of the assessments will be compared to the normal ranges. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition

    up to 28 days

  • Safety endpoint: will be assessed through collection and analysis of blood satturation

    units: %O2 Data management team will assess and review the vital signs : blood pressure \[mm Hg\], saturation \[%\], body temperature \[C\] , Each category of the assessments will be compared to the normal ranges. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition

    up to 28 days

  • Safety endpoint: will be assessed through collection and analysis of body temperature

    units: celsius degrees Data management team will assess and review the vital signs : blood pressure \[mm Hg\], saturation \[%\], body temperature \[C\] , Each category of the assessments will be compared to the normal ranges. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition

    up to 28 days

Secondary Outcomes (17)

  • Number of participants with depending on oxygen supplementation through day 28 since onset of symptoms

    up to 28 days

  • 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

    up to 7 days

  • Pharmacokinetic profile of the study drug

    on day 1 through 24 Hrs

  • Pharmacokinetic profile of the study drug - maximal concentartion

    on day 1 through 24 Hrs

  • Pharmacokinetic profile of the study drug - elimination rate constant (denoted as K)

    on day 1 through 24 Hrs

  • +12 more secondary outcomes

Study Arms (3)

Arm 1 - CimetrA-1

EXPERIMENTAL

CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).

Diagnostic Test: Biochemistry blood testDiagnostic Test: Hematology blood testDiagnostic Test: D-Dimer test (coagulation)Diagnostic Test: Inflammatory markersDiagnostic Test: Vital signsDiagnostic Test: VAS scaleDiagnostic Test: WHO Ordinal ScoreDiagnostic Test: COVID-19-Related Symptoms assessmentDiagnostic Test: COVID-19-Impact on Quality-of-Life QuestionnaireDiagnostic Test: POST- COVID-19 Functional Status Scale:Diagnostic Test: Pregnancy testDiagnostic Test: Physical examinationDiagnostic Test: PK parametersDiagnostic Test: SARS-CoV-2 test (PCR)Diagnostic Test: ECGDrug: Treatment administration (twice a day)

Arm 2 - CimetrA-2

EXPERIMENTAL

CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).

Diagnostic Test: Biochemistry blood testDiagnostic Test: Hematology blood testDiagnostic Test: D-Dimer test (coagulation)Diagnostic Test: Inflammatory markersDiagnostic Test: Vital signsDiagnostic Test: VAS scaleDiagnostic Test: WHO Ordinal ScoreDiagnostic Test: COVID-19-Related Symptoms assessmentDiagnostic Test: COVID-19-Impact on Quality-of-Life QuestionnaireDiagnostic Test: POST- COVID-19 Functional Status Scale:Diagnostic Test: Pregnancy testDiagnostic Test: Physical examinationDiagnostic Test: PK parametersDiagnostic Test: SARS-CoV-2 test (PCR)Diagnostic Test: ECGDrug: Treatment administration (twice a day)

Arm 3 - Placebo

PLACEBO COMPARATOR

Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).

Diagnostic Test: Biochemistry blood testDiagnostic Test: Hematology blood testDiagnostic Test: D-Dimer test (coagulation)Diagnostic Test: Inflammatory markersDiagnostic Test: Vital signsDiagnostic Test: VAS scaleDiagnostic Test: WHO Ordinal ScoreDiagnostic Test: COVID-19-Related Symptoms assessmentDiagnostic Test: COVID-19-Impact on Quality-of-Life QuestionnaireDiagnostic Test: POST- COVID-19 Functional Status Scale:Diagnostic Test: Pregnancy testDiagnostic Test: Physical examinationDiagnostic Test: PK parametersDiagnostic Test: SARS-CoV-2 test (PCR)Diagnostic Test: ECGDrug: Treatment administration (twice a day)

Interventions

Biochemistry blood testDIAGNOSTIC_TEST

preformed on days 1-14 and day 28. 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,

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
Hematology blood testDIAGNOSTIC_TEST

preformed on days 1-14 and day 28. complete CBC.

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
D-Dimer test (coagulation)DIAGNOSTIC_TEST

performed on days 1,2,7,14 and 28.

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
Inflammatory markersDIAGNOSTIC_TEST

performed on days 1-7, 14 and 28. IL-6, IL-1β, IL-12, TNF α, IFN-γ

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
Vital signsDIAGNOSTIC_TEST

performed on days 1-14 and day 28. blood pressure, pulse, weight, weight, body temperature (PO), saturation, respiratory rate.

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
VAS scaleDIAGNOSTIC_TEST

performed on all study visits. score: 0-10 ; a higher score indicates a higher pain level.

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
WHO Ordinal ScoreDIAGNOSTIC_TEST

performed on days 1,7,14 and 28. score: 0-3 ; a higher score indicates more symptoms.

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
COVID-19-Related Symptoms assessmentDIAGNOSTIC_TEST

performed on days 1,7,14,21 and 28. score: 0-3 ; a higher score indicates more symptoms.

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
COVID-19-Impact on Quality-of-Life QuestionnaireDIAGNOSTIC_TEST

performed on days 1,7,14,21 and 28. score: 1-5 ; a higher score indicates a lower quality of life.

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
POST- COVID-19 Functional Status Scale:DIAGNOSTIC_TEST

performed on day 28. score: 0-3 ; a higher score indicates better recovery.

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
Pregnancy testDIAGNOSTIC_TEST

performed on days 1 and 28. women of childbearing potential must undergo a urine pregnancy test.

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
Physical examinationDIAGNOSTIC_TEST

performed on days 1-14 and day 28. a full examination by a doctor.

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
PK parametersDIAGNOSTIC_TEST

performed on day 1. will be performed only on 14 patients that will agree to participate in the PK analysis (only for Brazil,Spain). The PK will be performed only for the first dose of drug, after patient received the first dose (5 puffs) the study staff need to follow the table below. For each test, approximately 5 ml of blood will be drawn (equivalent to one teaspoon)

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
SARS-CoV-2 test (PCR)DIAGNOSTIC_TEST

performed on days 1,14 and 28.

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
ECGDIAGNOSTIC_TEST

performed on days 1 and 28.

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo
Treatment administration (twice a day)DRUG

performed on days 1 and 2. twice a day, morning, and evening 1:1:1 ratio to study drug (CimetrA-1) (Arm 1) or study drug (CimetrA-2) or to Placebo (Arm 3)

Arm 1 - CimetrA-1Arm 2 - CimetrA-2Arm 3 - Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Confirmed by PCR test 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 (defined by NIH criteria - fever, cough, dyspnea, fast breathing, but no signs of severe pneumonia, including SpO2 ≥ 94% on room air).
  • Age: 18 years old and above.
  • Subjects must be hospitalized
  • Ability to receive treatment by spray into the oral cavity

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Rambam Medical Center

Haifa, Israel

Location

MeSH Terms

Conditions

COVID-19Coronavirus Infections

Interventions

Blood CoagulationVital SignsPregnancy TestsPhysical ExaminationCOVID-19 TestingElectrocardiography

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

HemostasisBlood Physiological PhenomenaCirculatory and Respiratory Physiological PhenomenaDiagnostic Techniques and ProceduresDiagnosisClinical Laboratory TechniquesDiagnostic Techniques, Obstetrical and GynecologicalInvestigative TechniquesHeart Function TestsDiagnostic Techniques, CardiovascularElectrodiagnosis

Study Officials

  • Rita Nadaf

    Galilee CBR - CRO

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Masking Details
This is a double-blind study: neither the participants nor the investigators will be aware of arm allocation of each study participant. Blindness is important to avoid bias. Monitoring and reporting of the success of blindness are important for the reader's confidence of the trial results. Groups should be marked by capital letter and blindness should maintain throughout the study.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 15, 2021

First Posted

September 8, 2021

Study Start

October 11, 2022

Primary Completion

January 21, 2023

Study Completion

March 1, 2023

Last Updated

March 15, 2023

Record last verified: 2023-03

Data Sharing

IPD Sharing
Will not share

Locations

IL(1)