This is a clinical trial to evaluate the safety, PK, viral shedding and clinical effects of Pentarlandir™ UPPTA in patients with early COVID-19. Approximately 90 ambulatory subjects with mildly symptomatic early COVID-19, who have been diagnosed with COVID-19 within the prior 4 days will be enrolled.
This is a clinical trial to evaluate the safety, PK, viral shedding and efficacy of PentarlandirTM UPPTA as a treatment for patients with early COVID-19. Approximately 90 ambulatory subjects with mildly symptomatic early COVID-19, who have been diagnosed with COVID-19 within the prior 48 hours, will be enrolled in the proof of principle study. Upon signing informed consent and evaluating medical history, concomitant medications, oxygen saturation (SaO2) at room air and vital signs, a focused physical examination of the heart and lungs will be performed. Subjects will be randomized into High-Dose, Low-Dose, and Placebo group in a 1:1:1 ratio at the final sample, but the enrollment will be staggered. In the first phase, 45 study subjects will be randomized at 2:1 ratio to Pentarlandir™ UPPTA low dose or placebo. After all the forty-five (45) subjects have completed the Day 21 assessment or early terminated (14-day dosing and 7 days of followed-up), DSMB will review the safety from the cohort and provide concurrence with proceeding with the higher dose cohort. If DSMB deems that the study is safe to proceed, another 45 subjects will be randomized at 2:1 ratio to Pentarlandir™ UPPTA high dose or placebo in the second phase. Both staggered cohorts will have the same stopping rules. During both phases of study, specimens for quantification of the viral genome, inflammatory markers, and safety laboratory tests will be collected. The IP will be dispensed to the study subjects and the subject will take the first dose of the study treatment at the clinic. Study subjects will be instructed (and provided) to use a device for ePRO for how to complete the patient-reported diary. The subjects will take the IP orally. Subjects in the low-dose group will take from each bottle of the active drug and placebo every 8 hours (q8h); for the high-dose group, from each of the two bottles of active drug; and for the placebo group, from each of the two bottles of placebo for 14 days. The first treatment dose should be taken within 4 days of COVID-19 diagnosis. Physical examination, specimen collection, laboratory evaluations and urine pregnancy test, vital signs, pulse oxygen saturation and clinical symptom and status determination will be conducted. Subjects who meet the eligibility criteria will be randomized. All subjects who fail to meet eligibility criteria are considered screen failures and are exited from the study without further evaluation. Screening and Randomization (V1, Day 1): After determining the eligibility, the study subjects will be randomized 2:1 to Pentarlandir™ UPPTA (either low or high dose) or placebo. The IP for treatment period will be dispensed to the study subjects and the subject will take the first dose of the study treatment at the study site. Study subjects will be instructed (and provided) how to complete the electronic patient reported outcome (ePRO) on a device. Treatment Period (V2 - V14 (EOT), Day 2 - Day 14): The subjects will continue to document the daily diary of ePRO. Total 13 visits are included in this period. Except 4 in-persons visits (V3, V7, V10, and V14), no in-person visit is expected during the study. Subjects will return to the clinical study sites to collect specimens for quantification of viral genome, inflammatory markers, pharmacokinetic and safety laboratory tests as well as record the SaO2, oral temperature, heart and respiratory rate, blood pressure, symptoms and concomitant medications, to document clinical status and adverse events (AEs), and IP accountability will be monitored. In addition, clinical symptom assessments and 7-category ordinal scale will be evaluated as well along with safety laboratory evaluations to determine whether the subject will continue to take the IP or stop the clinical trial. The subject will return the study treatment bottles at EOT visit. Except for the in-person visits, subjects will be phone-called once every day between 8:00 AM and 7:00 PM on the visits to record concomitant medications and to document clinical status and 7-category ordinal scale as well as adverse events (AEs) to determine whether the subject will be taken of the IP and/or stop the clinical trial. Weekly Follow-Up Period (V15 - V20, Day 15 - Day 56): Between Day 15 to 28, subjects will perform the ePRO diary daily. In addition to ePRO, study subjects will be called every 7±2 days after EOT visit to document final outcome and AEs up to Day 56. AE/SAEs, hospital and ICU lengths of stays, and mortality in hospitalized subjects will be documented.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
90
Pentarlandir™ UPPTA is a white oral capsule (with 188 mg of UPPTA)
The placebo of Pentarlandir™ UPPTA is a white oral capsule (without UPPTA)
Cullman Clinical Trials
Cullman, Alabama, United States
RECRUITINGCactus Clinical Research, Inc.
Gilbert, Arizona, United States
RECRUITINGChange from baseline in viral genome up to Day 14
Time frame: Baseline and Day14
Pharmacokinetics: Mean Concentration of Pentarlandir™ UPPTA on Days 3, 7, 10, 14.
Time frame: Day 3, 7, 10, and 14
Change from baseline in daily COVID-19-related symptom severity score through Day 28
A set of common COVID-19-related symptoms (see patient diary template for electronic Patient Report Outcome (ePRO)) will be evaluated daily by the patient regardless of which symptoms he/she had at baseline, as new symptoms may appear following the baseline assessment. (A Likert symptom scale will be developed using the (The 24 items reported in the ePRO, with potentially each item being normalized to 0 to 3 and the total score ranging from ranged 0 to 72))
Time frame: Baseline to Day 28
Number of days with substantial COVID-19-associated symptoms from start of study treatment (Day 1) based on self-assessment using daily symptom diary.
Substantial COVID-19-associated symptom days are defined as number of days when any symptoms score as moderate or sever in ePRO through Day 28
Time frame: 28 days
Number of days without COVID-19-associated symptoms in ePRO from Day 1-28 based on self- assessment using daily ePRO symptom diary.
Symptom-free days are defined as number of days when all the symptoms score as absent (or none) in ePRO through Day 28.
Time frame: 28 days
Number of days with limited COVID-19-associated symptoms in ePRO from Day 1-28 based on self- assessment using daily ePRO symptom diary.
Days with limited COVID-19-associated symptoms are defined as number of days when up to two symptoms score as mild or absent while the rest score as absent (or none) in ePRO through Day 28.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Synergy Healthcare
Bradenton, Florida, United States
RECRUITINGColumbus Clinical Services
Miami, Florida, United States
RECRUITINGC'A Research, LLC
Miami, Florida, United States
RECRUITINGCTMD Research
Palm Springs, Florida, United States
RECRUITINGEminat Research Group
Plantation, Florida, United States
RECRUITINGElite Medical Research
Dallas, Texas, United States
RECRUITINGDiversified Medical Practices
Houston, Texas, United States
RECRUITINGAccurate Clinical Research
Houston, Texas, United States
RECRUITING...and 2 more locations
Time frame: 28 days
Number of days with progression (or worsening) of COVID-19-associated symptoms in ePRO through Day 28 compared to baseline.
Progression or symptom worsening is defined as number of days when any symptoms scored as: 1. moderate at baseline but score as severe on any day through Day28. 2. mild at baseline but score as moderate or severe on any day through Day 28. 3. absent at baseline but score as mild, moderate or worse on any day through Day 28.
Time frame: Baseline to Day 28
Time to resolution, where resolution is defined as when a subject has scored absent (or none) on all COVID-19-associated symptoms for two consecutive days
Time frame: 28 days
Patient-reported global impression in ePRO
Patient-reported global impression in ePRO includes the following "In general, would you say that your health is excellent, very good, fair, or poor?" (The scores will be ranged between 1-5; excellent to poor)
Time frame: 28 days
Change from baseline in the patient's health status on a 7-category ordinal scale at up to Day 14
A 7-category ordinal scale of patient health status ranges from 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Time frame: Baseline to Day 14
Change from baseline in pulse oxygen saturation up to Day 14
Time frame: Baseline to Day 14