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This single-center, open-label, 2 arm parallel-group, randomized, interventional prospective exploratory study in 20 subjects aimed to evaluate safety and explore putative clinical benefits of Silmitasertib 1000 mg BID dose in patients with moderate COVID-19. Two-arm trial comparing the SOC/supportive care alone to the SOC/supportive care with addition of Silmitasertib (allocation ratio 1:1).
Silmitasertib is a first-in-class small molecule drug that targets Casein Kinase 2 (CK2). Protein kinase CK2 phosphorylates key proteins required to trigger mechanisms vital for viral replication and also is involved in development of host anti-viral immune response. SARS-CoV-2 viral proteins interacting with many human host proteins affect multiple innate immune pathways. One of these key proteins dysregulated by SARS-CoV-2 is the protein kinase CK2. SARS-COV-2 upregulates CK2 to support viral replication, avoid innate immune response and spread virus to nearby cells. Overactivation of CK2 indirectly contribute to successful viral replication and development of cytokine storm.SARs-Cov-2-induced overexpression of CK2, while pharmacological inhibition of CK2 suppresses virus proliferation. CK2 signaling appears to be an important pathway hijacked by SARS-CoV-2.
Emerging pre-clinical and clinical data and results of independent efficacy evaluation conducted by Utah State University and UCSF COVID-19 research group and Senhwa Biosciences hypothesize that Silmitasertib (CX-4945) could potentially quell virus-provoked aberrant hyperactivation of the innate immune system by inhibition of upregulated CK2 protein kinase, preferentially restoring normal host cell cytokine regulation, and attenuating viral replication in patients with moderate to severe COVID-19, thereby preventing disease progression and improving clinical outcomes. Intended target patient population for treatment with Silmitasertib (CX-4945) are SARS-COV-2 positive patients with moderate to severe COVID-19, since in the moderate to severe stage of the disease infected cells actively produce viral proteins that dysregulate signaling pathways to allow viruses to manipulate host immune responses to create an environment more favorable for infection, that may not be observed in the initial or mild stage of the disease.
CX-4945 demonstrated remarkable clinical benefits under emergency IND authorization in a patient with COVID-19 pneumonia not responsive to remdesivir, dexamethasone and antibiotics and requiring supplemental oxygen. The patient recovered and was discharged from the hospital in five days of treatment with CX-4945.
The purpose of this open-label, randomized, 2 arm parallel-group controlled, interventional prospective exploratory study in 20 subjects is to evaluate safety, tolerability and pharmacokinetics of Silmitasertib (CX-4945) 1000 mg BID dose, to compare time to clinical recovery, and putative clinical benefit across treatment groups, and to evaluate anti-viral activities in COVID-19 patients.
Silmitasertib is a generally well-tolerated medication. Most adverse events reported were mild to moderate in severity. The most common toxicities associated with CX-4945 were gastrointestinal disorders, manageable with drug discontinuation or use of anti-diarrheal medication. Based on the currently available data, the identified or potential risks of the product do not outweigh its identified or potential benefits.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Experimental | Group A will receive the best supportive care and/or recommended standard of care (at this point no standard of care drugs are recommended by CDC for patients with moderate COVID-19) in combination with the study drug Silmitasertib |
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| Group B | Active Comparator | Group B (control) that will receive the same care as the Group A but without Silmitasertib |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Silmitasertib | Drug | Capsules |
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| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]) Within the CX-4945 Treatment Group | To assess adverse events associated with the administration of CX-4945 orally, twice daily to patients with moderate COVID-19. The occurrence of overall AEs in the two treatment groups are summarized. | From randomization (Day 1) to Day 60 |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Recovery Associated With COVID-19 Within the CX-4945 Treatment Group | To compare the number of days to clinical recovery specifically associated with COVID-19 in the CX-4945 treatment group as compared to the control arm by Day 14 of the study. | First 14 days of the study. |
| Anti-Viral Activity of CX-4945 |
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Inclusion Criteria:
Male or non-pregnant female adult ≥ 18 years of age
Diagnosed with COVID-19 by standard RT-PCR assay or equivalent testing
Outpatient subjects with moderate illness caused by SARS-CoV-2 infection as defined below,
At least two of the key COVID-19-related symptoms with score 2 or higher (0=none, 1=mild, 2=moderate, and 3=severe): cough, sore throat, malaise, headache, muscle pain, fever, neurological symptoms such as brain fog/concentration challenges, gastrointestinal symptoms or shortness of breath with exertion
AND
AND
Patient (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
Adequate hematopoietic capacity, as defined by the following:
Adequate hepatic function, as defined by the following:
Adequate renal function, as defined by the following:
a. Renal: calculated creatinine clearance >45 mL/min for patients with abnormal, increased creatinine levels (Cockcroft-Gault formula).
Ability to take oral medication and be willing to adhere to drug administration and premedication requirements (see Section 6.3) throughout study duration.
Exclusion Criteria:
Any signs indicative of Severe or Critical Illness Severity required hospitalization as defined below:
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| Name | Affiliation | Role |
|---|---|---|
| Chris P. Recknor, MD | Center for Advanced Research and Education | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Advanced Research and Education | Gainesville | Georgia | 30501 | United States |
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30 Nov 2020 - First Patient First Visit; 04 Oct 2021 - Last Patient Last Visit.
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| ID | Title | Description |
|---|---|---|
| FG000 | Group A | Group A will receive the best supportive care and/or recommended standard of care (at this point no standard of care drugs are recommended by CDC for patients with moderate COVID-19) in combination with the study drug Silmitasertib. Silmitasertib: Capsules 1000mg/BID |
| FG001 | Group B | Group B (control) that will receive the same care as the Group A but without Silmitasertib SOC: Some therapeutics for COVID-19 are available through EUA. SOC treatment availability is expected to change during the course of this trial. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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The ITT population was defined as all randomized subjects. This population was used as the primary analysis population for analysis of the primary and secondary efficacy endpoints.
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| ID | Title | Description |
|---|---|---|
| BG000 | Group A | Group A will receive the best supportive care and/or recommended standard of care (at this point no standard of care drugs are recommended by CDC for patients with moderate COVID-19) in combination with the study drug Silmitasertib. Silmitasertib: Capsules 1000mg/BID |
| BG001 | Group B |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]) Within the CX-4945 Treatment Group | To assess adverse events associated with the administration of CX-4945 orally, twice daily to patients with moderate COVID-19. The occurrence of overall AEs in the two treatment groups are summarized. | Population: Safety Population; The Safety population is defined as any subject receiving at least one dose of CX-4945 or standard of care treatment after randomization. | Posted | Count of Participants | Participants | From randomization (Day 1) to Day 60 |
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From randomization (Day 1) to Day 60
Adverse events occurring from randomization (Day 1) to Day 60 (including vital signs, physical findings, clinical laboratory, and ECG results) as characterized by type, frequency, severity [(as graded by Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (https://www.fda.gov/media/73679/download)\], timing, seriousness, and relationship to study therapy.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group A | Group A will receive the best supportive care and/or recommended standard of care (at this point no standard of care drugs are recommended by CDC for patients with moderate COVID-19) in combination with the study drug Silmitasertib Silmitasertib: Capsules |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 | Infections and infestations | MedDRA version 24.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA version 24.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kacy Huang, Director of Clinical Department | Senhwa Biosciences, Inc. | +886-2-8911-9856 | 214 | kacyhuang@senhwabio.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 11, 2021 | Sep 19, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 25, 2022 | Sep 19, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C555142 | silmitasertib |
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| SOC |
| Drug |
Some therapeutics for COVID-19 are available through EUA. SOC treatment availability is expected to change during the course of this trial. |
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To evaluate preliminary evidence of anti-viral activity of CX-4945 as compared to the control arm. |
| Quantitative changes in viral load from Day 1 to Day 28. |
| Maximum Plasma Concentration [Cmax] of CX-4945 | To evaluate the maximum plasma concentration of CX-4945 when given at 1000 mg BID PO (Experimental Arm taking CX-4945 only i.e. Group A). | Plasma sample of CX-4945 are collected at the following timepoints: Day 1: pre-dose, 1, 2, 3, 6 and 24 hours post Day 1 morning dose and Day 14: pre-dose, 1, 2, 3, 6, 24, 48 and 72 hours post Day 14 morning dose. |
| Time to Maximum Observed Plasma Concentration [Tmax] of CX-4945 | To evaluate the time to maximum observed plasma concentration of CX-4945 when given at 1000 mg BID PO (Experimental Arm taking CX-4945 only i.e. Group A). | Plasma sample of CX-4945 are collected at the following timepoints: Day 1: pre-dose, 1, 2, 3, 6 and 24 hours post Day 1 morning dose and Day 14: pre-dose, 1, 2, 3, 6, 24, 48 and 72 hours post Day 14 morning dose. |
| Area Under the Concentration-Time Curve [AUC0-6] of CX-4945 | To evaluate the area under the concentration-time curve [AUC0-6] of CX-4945 when given at 1000 mg BID PO (Experimental Arm taking CX-4945 only i.e. Group A). | Plasma sample of CX-4945 are collected at the following timepoints: Day 1: pre-dose, 1, 2, 3, 6 and 24 hours post Day 1 morning dose and Day 14: pre-dose, 1, 2, 3, 6, 24, 48 and 72 hours post Day 14 morning dose. |
| Clinical Benefit of CX-4945 i.e. All-cause Mortality Status - the Number of Deaths Occurred in Each Treatment Group From Randomization (Day 1) Through Day 60 | Between the experimental arm with CX-4945 and the control arm, moderate COVID-19 patients' health status will be evaluated in terms of all-cause mortality. Mortality status and cause will be assessed by study staff and the information will be documented on a Clinical Status questionnaire. The data collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in all-cause mortality between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | From Randomization (Day 1) through Day 60 |
| Clinical Benefit of CX-4945 i.e. Number of Respiratory Failures Occurred in Each Treatment Group From Randomization (Day 1) Through Day 45 | Between the experimental arm with CX-4945 and the control arm, moderate COVID-19 patients' health status will be evaluated in terms of the number of respiratory failures. Respiratory failures will be assessed by study staff and the information will be documented on a Clinical Status questionnaire. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in number of respiratory failures between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | From Randomization (Day 1) through Day 45 |
| Clinical Benefit of CX-4945 i.e. Number of Subjects Hospitalized in Each Treatment Group From Randomization (Day 1) to Day 45 | Between the experimental arm with CX-4945 and the control arm, patients will be evaluated in terms of the number of subjects hospitalized in each treatment group. The number of subjects hospitalized will be assessed and the information will be documented on a clinical status questionnaire. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in number of subjects hospitalized between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | From Randomization (Day 1) to Day 45 |
| Clinical Benefit of CX-4945 i.e. Number of Days to Normalization of Oxygen Saturation Level Measured by Pulse Oximeter at Randomization (Day 1), Day 4, Day 8, Day 11, Day 14, Day 28 and Day 45 and Categorized as <96% Versus ≥96%. | Between the experimental arm with CX-4945 and the control arm, patients will be evaluated in terms of time to oxygen saturation level normalization. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in time to oxygen saturation level normalization between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. Best Case Scenario = Days to first response for responder, = Days to last observation for non-responder (censored); Worst Case Scenario = Days to first response for responder, = Days to planned last observation date (31 for EQ-5D-5L and SARS-COV-2 Viral Clearance at visit 7, 45 for others at visit 8) for non-responder (censored); Days to first response = date of first response - the first treatment date/time + 1 Days to last observation = date of last evaluation - the first treatment date/time + 1 For Arm SOC, the first treatment date is the date of visit 2. | Randomization (Day 1), Day 4, Day 8, Day 11, Day 14, Day 28 and Day 45 |
| Clinical Benefit of CX-4945 i.e. Proportion of Subjects With Disease Progression or Improvement in Health Status Occurring From Randomization (Day 1) to Day 28. | Between the experimental arm with CX-4945 and the control arm, proportion of subjects with disease progression or improvement in health status occurring from Randomization (Day 1) to Day 28 will be evaluated. Disease progression is defined as change in subject health status assessment from item 7 to items 1- 6 and health improvement -as change from item 7 to item 8, evaluated by the ordinal NIAID 8- point Clinical Progression Outcomes scale - collected at every visit from randomization (Day 1) through Day 45. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in clinical status between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | From Randomization (Day 1) to Day 28 |
| Clinical Benefit of CX-4945 i.e. Changes in the Total Score for Q1~Q5 of the EQ-D5-5L From Randomization (Day 1) to Day 8, Day 14 and Day 28. | Changes in the total score for Q1~Q5 of the EQ-D5-5L (used as an indicator of symptom improvement) from Baseline (Day 1) to Day 8, 14, 28 were evaluated. The 5-level EQ-5D version (EQ-5D-5L) was used to assess five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Four times during the study (baseline, Day 8, Day 14 and Day 28) the patients were asked to complete health status survey by answering 6 questions about their health and quality of life. The scale measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Patients were also asked to assess their overall health status by selecting a number between 1 and 100 to describe the condition of their health, 100 being the best imaginable. | From randomization (Day 1) to Day 8, Day 14 and Day 28. |
| Clinical Benefit of CX-4945 i.e. Changes in the Imaginable Health Status of the EQ-D5-5L From Randomization (Day 1) to Day 8, Day 14 and Day 28. | Changes in the Imaginable Health Status of the EQ-D5-5L (used as an indicator of symptom improvement) from Baseline (Day 1) to Day 8, 14, 28 were evaluated. The 5-level EQ-5D version (EQ-5D-5L) was used to assess five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Four times during the study (baseline, Day 8, Day 14 and Day 28) the patients were asked to complete health status survey by answering 6 questions about their health and quality of life. Patients were also asked to assess their overall health status by selecting a number between 1 and 100 to describe the condition of their health, 100 being the best imaginable. | From randomization (Day 1) to Day 8, Day 14 and Day 28. |
| CX-4945 Inflammatory Marker Outcomes i.e. Plasma IL-6 | Labs to evaluate changes in plasma IL-6 (interleukin-6 in ng/L) levels between the patients within the experimental arm with CX-4945 and the control arm, of patients with moderate COVID-19. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in plasma IL-6 levels between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Changes in plasma IL-6 level from Randomization (Day 1) to Day 4, Day 8, Day 11, and Day 14. |
| CX-4945 Inflammatory Marker Outcomes i.e. Plasma CRP | Labs to evaluate changes in plasma CRP (C-reactive protein in mg/DL) levels between the patients within the experimental arm with CX-4945 and the control arm, of patients with moderate COVID-19. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in plasma CRP levels between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Changes in CRP from randomization (Day 1) to Day 4, Day 8, Day 11, and Day 14. |
| CX-4945 Inflammatory Marker Outcomes i.e. Plasma LDH | Labs to evaluate changes in plasma LDH (lactic acid dehydrogenase in U/L) levels between the patients within the experimental arm with CX-4945 and the control arm, of patients with moderate COVID-19. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in plasma LDH levels between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Changes in LDH from randomization (Day 1) to Day 4, Day 8, Day 11, and Day 14. |
| CX-4945 Inflammatory Marker Outcomes i.e. Plasma CPK | Labs to evaluate changes in plasma CPK (creatine phosphokinase in U/L) levels between the patients within the experimental arm with CX-4945 and the control arm, of patients with moderate COVID-19. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in plasma CPK levels between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Changes in CPK from randomization (Day 1) to Day 4, Day 8, Day 11, and Day 14. |
| CX-4945 Inflammatory Marker Outcomes i.e. Plasma Ferritin | Labs to evaluate changes in plasma ferritin (μg/L) levels between the patients within the experimental arm with CX-4945 and the control arm, of patients with moderate COVID-19. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in plasma ferritin levels between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Changes in ferritin from randomization (Day 1) to Day 4, Day 8, Day 11, and Day 14. |
| CX-4945 Inflammatory Marker Outcomes i.e. Plasma D-Dimer | Labs to evaluate changes in plasma D-dimer (μg/mL) levels between the patients within the experimental arm with CX-4945 and the control arm, of patients with moderate COVID-19. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in plasma D-dimer levels between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Changes in D-dimer from randomization (Day 1) to Day 4, Day 8, Day 11, and Day 14. |
Group B (control) that will receive the same care as the Group A but without Silmitasertib SOC: Some therapeutics for COVID-19 are available through EUA. SOC treatment availability is expected to change during the course of this trial. |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Study Site | Count of Participants | Participants |
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| OG001 | Group B | Group B (control) that will receive the same care as the Group A but without Silmitasertib SOC: Some therapeutics for COVID-19 are available through EUA. SOC treatment availability is expected to change during the course of this trial. |
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| Secondary | Clinical Recovery Associated With COVID-19 Within the CX-4945 Treatment Group | To compare the number of days to clinical recovery specifically associated with COVID-19 in the CX-4945 treatment group as compared to the control arm by Day 14 of the study. | 2 patients in Group A, 3 patients in Group B were censored from this analysis per protocol. | Posted | Median | 95% Confidence Interval | Days | First 14 days of the study. |
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| Secondary | Anti-Viral Activity of CX-4945 | To evaluate preliminary evidence of anti-viral activity of CX-4945 as compared to the control arm. | Posted | Count of Participants | Participants | Quantitative changes in viral load from Day 1 to Day 28. |
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| Secondary | Maximum Plasma Concentration [Cmax] of CX-4945 | To evaluate the maximum plasma concentration of CX-4945 when given at 1000 mg BID PO (Experimental Arm taking CX-4945 only i.e. Group A). | Plasma sample of CX-4945 are collected from the first four subjects randomized to treatment arm A. | Posted | Mean | Standard Deviation | ng/mL | Plasma sample of CX-4945 are collected at the following timepoints: Day 1: pre-dose, 1, 2, 3, 6 and 24 hours post Day 1 morning dose and Day 14: pre-dose, 1, 2, 3, 6, 24, 48 and 72 hours post Day 14 morning dose. |
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| Secondary | Time to Maximum Observed Plasma Concentration [Tmax] of CX-4945 | To evaluate the time to maximum observed plasma concentration of CX-4945 when given at 1000 mg BID PO (Experimental Arm taking CX-4945 only i.e. Group A). | Plasma sample of CX-4945 are collected from the first four subjects randomized to treatment arm A. | Posted | Mean | Standard Deviation | h | Plasma sample of CX-4945 are collected at the following timepoints: Day 1: pre-dose, 1, 2, 3, 6 and 24 hours post Day 1 morning dose and Day 14: pre-dose, 1, 2, 3, 6, 24, 48 and 72 hours post Day 14 morning dose. |
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| Secondary | Area Under the Concentration-Time Curve [AUC0-6] of CX-4945 | To evaluate the area under the concentration-time curve [AUC0-6] of CX-4945 when given at 1000 mg BID PO (Experimental Arm taking CX-4945 only i.e. Group A). | Plasma sample of CX-4945 are collected from the first four subjects randomized to treatment arm A. | Posted | Mean | Standard Deviation | h*ng/mL | Plasma sample of CX-4945 are collected at the following timepoints: Day 1: pre-dose, 1, 2, 3, 6 and 24 hours post Day 1 morning dose and Day 14: pre-dose, 1, 2, 3, 6, 24, 48 and 72 hours post Day 14 morning dose. |
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| Secondary | Clinical Benefit of CX-4945 i.e. All-cause Mortality Status - the Number of Deaths Occurred in Each Treatment Group From Randomization (Day 1) Through Day 60 | Between the experimental arm with CX-4945 and the control arm, moderate COVID-19 patients' health status will be evaluated in terms of all-cause mortality. Mortality status and cause will be assessed by study staff and the information will be documented on a Clinical Status questionnaire. The data collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in all-cause mortality between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Population: Intent-to-Treat (ITT) Population; The Intent-to-Treat (ITT) population is defined as all randomized subjects. | Posted | Count of Participants | Participants | No | From Randomization (Day 1) through Day 60 |
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| Secondary | Clinical Benefit of CX-4945 i.e. Number of Respiratory Failures Occurred in Each Treatment Group From Randomization (Day 1) Through Day 45 | Between the experimental arm with CX-4945 and the control arm, moderate COVID-19 patients' health status will be evaluated in terms of the number of respiratory failures. Respiratory failures will be assessed by study staff and the information will be documented on a Clinical Status questionnaire. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in number of respiratory failures between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Population: Intent-to-Treat (ITT) Population; The Intent-to-Treat (ITT) population is defined as all randomized subjects. | Posted | Count of Participants | Participants | From Randomization (Day 1) through Day 45 |
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| Secondary | Clinical Benefit of CX-4945 i.e. Number of Subjects Hospitalized in Each Treatment Group From Randomization (Day 1) to Day 45 | Between the experimental arm with CX-4945 and the control arm, patients will be evaluated in terms of the number of subjects hospitalized in each treatment group. The number of subjects hospitalized will be assessed and the information will be documented on a clinical status questionnaire. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in number of subjects hospitalized between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Population: Intent-to-Treat (ITT) Population; The Intent-to-Treat (ITT) population is defined as all randomized subjects. | Posted | Count of Participants | Participants | From Randomization (Day 1) to Day 45 |
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| Secondary | Clinical Benefit of CX-4945 i.e. Number of Days to Normalization of Oxygen Saturation Level Measured by Pulse Oximeter at Randomization (Day 1), Day 4, Day 8, Day 11, Day 14, Day 28 and Day 45 and Categorized as <96% Versus ≥96%. | Between the experimental arm with CX-4945 and the control arm, patients will be evaluated in terms of time to oxygen saturation level normalization. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in time to oxygen saturation level normalization between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. Best Case Scenario = Days to first response for responder, = Days to last observation for non-responder (censored); Worst Case Scenario = Days to first response for responder, = Days to planned last observation date (31 for EQ-5D-5L and SARS-COV-2 Viral Clearance at visit 7, 45 for others at visit 8) for non-responder (censored); Days to first response = date of first response - the first treatment date/time + 1 Days to last observation = date of last evaluation - the first treatment date/time + 1 For Arm SOC, the first treatment date is the date of visit 2. | Population: Intent-to-Treat (ITT) Population; The Intent-to-Treat (ITT) population is defined as all randomized subjects. | Posted | Mean | Standard Error | days | Randomization (Day 1), Day 4, Day 8, Day 11, Day 14, Day 28 and Day 45 |
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| Secondary | Clinical Benefit of CX-4945 i.e. Proportion of Subjects With Disease Progression or Improvement in Health Status Occurring From Randomization (Day 1) to Day 28. | Between the experimental arm with CX-4945 and the control arm, proportion of subjects with disease progression or improvement in health status occurring from Randomization (Day 1) to Day 28 will be evaluated. Disease progression is defined as change in subject health status assessment from item 7 to items 1- 6 and health improvement -as change from item 7 to item 8, evaluated by the ordinal NIAID 8- point Clinical Progression Outcomes scale - collected at every visit from randomization (Day 1) through Day 45. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in clinical status between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Population: Intent-to-Treat (ITT) Population; The Intent-to-Treat (ITT) population is defined as all randomized subjects. | Posted | Count of Participants | Participants | From Randomization (Day 1) to Day 28 |
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| Secondary | Clinical Benefit of CX-4945 i.e. Changes in the Total Score for Q1~Q5 of the EQ-D5-5L From Randomization (Day 1) to Day 8, Day 14 and Day 28. | Changes in the total score for Q1~Q5 of the EQ-D5-5L (used as an indicator of symptom improvement) from Baseline (Day 1) to Day 8, 14, 28 were evaluated. The 5-level EQ-5D version (EQ-5D-5L) was used to assess five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Four times during the study (baseline, Day 8, Day 14 and Day 28) the patients were asked to complete health status survey by answering 6 questions about their health and quality of life. The scale measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Patients were also asked to assess their overall health status by selecting a number between 1 and 100 to describe the condition of their health, 100 being the best imaginable. | Population: Intent-to-Treat (ITT) Population; The Intent-to-Treat (ITT) population is defined as all randomized subjects. | Posted | Mean | Standard Deviation | score on a scale | From randomization (Day 1) to Day 8, Day 14 and Day 28. |
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| Secondary | Clinical Benefit of CX-4945 i.e. Changes in the Imaginable Health Status of the EQ-D5-5L From Randomization (Day 1) to Day 8, Day 14 and Day 28. | Changes in the Imaginable Health Status of the EQ-D5-5L (used as an indicator of symptom improvement) from Baseline (Day 1) to Day 8, 14, 28 were evaluated. The 5-level EQ-5D version (EQ-5D-5L) was used to assess five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Four times during the study (baseline, Day 8, Day 14 and Day 28) the patients were asked to complete health status survey by answering 6 questions about their health and quality of life. Patients were also asked to assess their overall health status by selecting a number between 1 and 100 to describe the condition of their health, 100 being the best imaginable. | Population: Intent-to-Treat (ITT) Population; The Intent-to-Treat (ITT) population is defined as all randomized subjects. | Posted | Mean | Standard Deviation | score on a scale | From randomization (Day 1) to Day 8, Day 14 and Day 28. |
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| Secondary | CX-4945 Inflammatory Marker Outcomes i.e. Plasma IL-6 | Labs to evaluate changes in plasma IL-6 (interleukin-6 in ng/L) levels between the patients within the experimental arm with CX-4945 and the control arm, of patients with moderate COVID-19. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in plasma IL-6 levels between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Population: Safety Population; The Safety population is defined as any subject receiving at least one dose of CX-4945 or standard of care treatment after randomization. | Posted | Mean | Standard Deviation | ng/L | Changes in plasma IL-6 level from Randomization (Day 1) to Day 4, Day 8, Day 11, and Day 14. |
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| Secondary | CX-4945 Inflammatory Marker Outcomes i.e. Plasma CRP | Labs to evaluate changes in plasma CRP (C-reactive protein in mg/DL) levels between the patients within the experimental arm with CX-4945 and the control arm, of patients with moderate COVID-19. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in plasma CRP levels between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Population: Safety Population; The Safety population is defined as any subject receiving at least one dose of CX-4945 or standard of care treatment after randomization. | Posted | Mean | Standard Deviation | mg/dL | Changes in CRP from randomization (Day 1) to Day 4, Day 8, Day 11, and Day 14. |
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| Secondary | CX-4945 Inflammatory Marker Outcomes i.e. Plasma LDH | Labs to evaluate changes in plasma LDH (lactic acid dehydrogenase in U/L) levels between the patients within the experimental arm with CX-4945 and the control arm, of patients with moderate COVID-19. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in plasma LDH levels between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Population: Safety Population; The Safety population is defined as any subject receiving at least one dose of CX-4945 or standard of care treatment after randomization. | Posted | Mean | Standard Deviation | U/L | Changes in LDH from randomization (Day 1) to Day 4, Day 8, Day 11, and Day 14. |
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| Secondary | CX-4945 Inflammatory Marker Outcomes i.e. Plasma CPK | Labs to evaluate changes in plasma CPK (creatine phosphokinase in U/L) levels between the patients within the experimental arm with CX-4945 and the control arm, of patients with moderate COVID-19. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in plasma CPK levels between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Population: Safety Population; The Safety population is defined as any subject receiving at least one dose of CX-4945 or standard of care treatment after randomization. | Posted | Mean | Standard Deviation | U/L | Changes in CPK from randomization (Day 1) to Day 4, Day 8, Day 11, and Day 14. |
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| Secondary | CX-4945 Inflammatory Marker Outcomes i.e. Plasma Ferritin | Labs to evaluate changes in plasma ferritin (μg/L) levels between the patients within the experimental arm with CX-4945 and the control arm, of patients with moderate COVID-19. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in plasma ferritin levels between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Population: Safety Population; The Safety population is defined as any subject receiving at least one dose of CX-4945 or standard of care treatment after randomization. | Posted | Mean | Standard Deviation | μg/L | Changes in ferritin from randomization (Day 1) to Day 4, Day 8, Day 11, and Day 14. |
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| Secondary | CX-4945 Inflammatory Marker Outcomes i.e. Plasma D-Dimer | Labs to evaluate changes in plasma D-dimer (μg/mL) levels between the patients within the experimental arm with CX-4945 and the control arm, of patients with moderate COVID-19. The information collected will be analyzed at the conclusion of the study to determine if there is a statistically significant difference in plasma D-dimer levels between those whose treatment included CX-4945 and those whose treatment did not include CX-4945. | Population: Safety Population; The Safety population is defined as any subject receiving at least one dose of CX-4945 or standard of care treatment after randomization. | Posted | Mean | Standard Deviation | μg/mL | Changes in D-dimer from randomization (Day 1) to Day 4, Day 8, Day 11, and Day 14. |
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| 0 |
| 10 |
| 1 |
| 10 |
| 8 |
| 10 |
| EG001 | Group B | Group B (control) that will receive the same care as the Group A but without Silmitasertib SOC: Some therapeutics for COVID-19 are available through EUA. SOC treatment availability is expected to change during the course of this trial. | 0 | 10 | 1 | 10 | 4 | 10 |
| COVID-19 pneumonia | Infections and infestations | MedDRA version 24.1 | Systematic Assessment |
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| Photopsia | Eye disorders | MedDRA version 24.1 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA version 24.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA version 24.1 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA version 24.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA version 24.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA version 24.1 | Systematic Assessment |
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| Dyschezia | Gastrointestinal disorders | MedDRA version 24.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA version 24.1 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA version 24.1 | Systematic Assessment |
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| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA version 24.1 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA version 24.1 | Systematic Assessment |
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| Hepatitis viral | Infections and infestations | MedDRA version 24.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA version 24.1 | Systematic Assessment |
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| Viral infection | Infections and infestations | MedDRA version 24.1 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA version 24.1 | Systematic Assessment |
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| Glucose urine present | Investigations | MedDRA version 24.1 | Systematic Assessment |
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| Haemoglobin increased | Investigations | MedDRA version 24.1 | Systematic Assessment |
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| Hepatic enzyme increased | Investigations | MedDRA version 24.1 | Systematic Assessment |
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| Platelet count increased | Investigations | MedDRA version 24.1 | Systematic Assessment |
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| Urine analysis abnormal | Investigations | MedDRA version 24.1 | Systematic Assessment |
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| Hyperalbuminaemia | Metabolism and nutrition disorders | MedDRA version 24.1 | Systematic Assessment |
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| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA version 24.1 | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA version 24.1 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA version 24.1 | Systematic Assessment |
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| Metabolic acidosis | Metabolism and nutrition disorders | MedDRA version 24.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version 24.1 | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA version 24.1 | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA version 24.1 | Systematic Assessment |
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Not provided
Not provided
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| Inconclusive |
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| Not Evaluated |
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| Viral Clearance Day 14 (EOT) |
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| Worst Case Scenario |
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| Progression |
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| Else |
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| Baseline to Visit 8 (Day 45), LOCF |
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| Visit 6 (Day 14, EOT) - Visit 2 (Day 1) |
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| Visit 7 (Day 28, F1), LOCF - Visit 2 (Day 1) |
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| Visit 6 (Day 14, EOT) - Visit 2 (Day 1) |
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| Visit 7 (Day 28, F1), LOCF - Visit 2 (Day 1) |
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| Adjusted Visit 4 (Day 8) - Baseline |
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| Adjusted Visit 5 (Day 11) - Baseline |
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| Adjusted Visit 6 (Day 14) - Baseline |
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| Adjusted Visit 4 (Day 8) - Baseline |
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| Adjusted Visit 5 (Day 11) - Baseline |
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| Adjusted Visit 6 (Day 14) - Baseline |
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| Adjusted Visit 4 (Day 8) - Baseline |
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| Adjusted Visit 5 (Day 11) - Baseline |
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| Adjusted Visit 6 (Day 14) - Baseline |
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| Adjusted Visit 4 (Day 8) - Baseline |
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| Adjusted Visit 5 (Day 11) - Baseline |
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| Adjusted Visit 6 (Day 14) - Baseline |
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| Adjusted Visit 4 (Day 8) - Baseline |
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| Adjusted Visit 5 (Day 11) - Baseline |
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| Adjusted Visit 6 (Day 14) - Baseline |
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| Adjusted Visit 4 (Day 8) - Baseline |
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| Adjusted Visit 5 (Day 11) - Baseline |
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| Adjusted Visit 6 (Day 14) - Baseline |
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