A Randomized, Double-Blind, Placebo-Controlled, Proof of Principle Study of Pentarlandir™ UPPTA for the Treatment of Patients With Early COVID-19
试验速览
- 阶段
- 2 期
- 入组人数
- 90
- 试验地点
- 12
- 主要终点
- Change from baseline in viral genome up to Day 14
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women 18 years of age or older.
- •Able and willing to provide informed consent.
- •Able and willing to sufficiently operate smart phones and study-provided monitoring devices per the Investigator.
- •Early COVID-19 diagnosis with mild severity defined as meeting all of the below:
- •Confirmation of COVID-19 by a PCR-based diagnostic within 4 days of randomization.
- •COVID-19 with mild symptoms, defined as a score of 8 or higher on the clinical symptom score.
- •Clinical symptom score includes 9 items in fever or chills, myalgia, cough, headache, sore throat, new loss of test or smell, gastrointestinal symptoms (nausea, vomiting, diarrhea or abdominal pain), congestion or running nose, and fatigue (malaise) as assessed and recorded by the investigator.
- •Note: The total score per patient ranges from 0 to 27 points. Each symptom is rated from 0 to
- •[0 = none, 1 = mild, 2 = moderate, and 3 = severe]
- •No signs of a more serious lower airway disease per clinical exam, chest X-ray or chest CT.
- •Resting RR ≤ 20, HR ≤ 90, oxygen saturation (pulse oximetry) ≥ 95% on room air.
- •For women of childbearing potential (women who are not permanently sterile [documented hysterectomy, bilateral tubal ligation, salpingectomy, or oophorectomy] or postmenopausal [12 months with no menses without an alternative medical cause]):
- •Negative urine pregnancy test at screening.
- •Willingness to practice a highly effective method of contraception that includes, but is not limited to, abstinence, sex only with persons of the same sex, monogamous relationship with a postmenopausal partner, monogamous relationship with vasectomize partner, vasectomy, licensed hormonal methods, intrauterine device, or consistent use of a barrier method (e.g., condom, diaphragm) with spermicide for 28 days after the last dose of study medication.
- •Ability and willingness to comply with all aspects of the study through the entire study period.
排除标准
- •Patient is either asymptomatic or with baseline severity of moderate, sever, or critical COVID-
- •Pregnant or lactating women.
- •Patients with shortness of breath at rest.
- •Findings on physical examination or available imaging studies suggesting rapid disease progression of COVID-
- •Signs or symptoms indicative of pneumonia or any other lower respiratory tract disorders, or clinically significant findings in available lung imaging studies suggestive of such disorders.
- •Need for immediate hospitalization, oxygen supplementation or mechanical ventilation.
- •Obstructive airway diseases, including chronic obstructive pulmonary disease (COPD) and asthma, or other respiratory disease that could exacerbate independent of COVID-
- •Use of remdesivir, chloroquine, hydroxychloroquine, convalescent plasma, other monoclonal antibody therapies, include REGEN-COV (casirivimab and imdevimab), bamlanivimab (plus etesevimab), dexamethasone, ivermectin, baricitinib, and other Janus kinase inhibitors, Bruton's tyrosine kinase inhibitors, tocilizumab (and other interleukin-6 inhibitors) and any other therapy with EUA or approval and other investigational agents for COVID-
- •Patients who are participating in other clinical trials.
- •History of conditions associated with immunocompromise, or treatments known to affect the immune system, including but not limited to oral or intravenous corticosteroids, alkylating drugs, antimetabolites, cytotoxic drugs, other chemotherapy, radiation, immune-modulating biologics, within 30 days of screening.
- •Barium enemas within the last 30 days.
- •Taking OTC or prescribed medicine which has compound as active ingredient.
- •Any unstable or uncontrolled medical illnesses such as neurological disorders, cardiovascular disorders, diabetes, hepatic or renal disorders that per the Investigator would intervene with the study conduct or study results interpretation.
- •Any other medical, psychiatric, or social condition or occupational or other responsibility that in the judgment of the Investigator would interfere with or serve as a contraindication to protocol adherence, assessment of safety, or a patient's ability to give informed consent or respond to the study procedures or questions during the personal visits or the video calls.
- •High-risk individuals are those who meet at least one of the following criteria:
- •Aged ≥ 65 years
- •Body mass index (BMI) > 30
- •Chronic kidney disease
- •Immunosuppressive disease or immunosuppressive treatment
- •Cardiovascular disease (including congenital heart disease) or hypertension
- •Chronic lung diseases (for example, chronic obstructive pulmonary disease, asthma [moderate-to-severe], interstitial lung disease, cystic fibrosis and pulmonary hypertension)
- •Sickle cell disease
- •Neurodevelopmental disorders (for example, cerebral palsy) or other conditions that confer medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies)
- •Having a medical-related technological dependence (for example, tracheostomy, gastrostomy, or positive pressure ventilation [not related to COVID-19]
- •Exclusion is not limited to the medical conditions or factors listed above. The investigators have to consider the benefit-risk for an individual patient to determine other medical conditions or factors (for example, overweight, race or ethnicity) may also place individual patients at high risk for progression to severe COVID-19 and be excluded.
研究组 & 干预措施
Pentarlandir™ UPPTA - High Dose
High dose of Pentarlandir™ UPPTA, q8h (over 3 hours postprandially)
干预措施: Pentarlandir™ UPPTA (Drug)
Pentarlandir™ UPPTA - Low Dose
Low dose of Pentarlandir™ UPPTA and placebo, q8h (over 3 hours postprandially)
干预措施: Pentarlandir™ UPPTA (Drug)
Pentarlandir™ UPPTA - Low Dose
Low dose of Pentarlandir™ UPPTA and placebo, q8h (over 3 hours postprandially)
干预措施: Placebo (Drug)
Placebo
Pacebo, q8h (over 3 hours postprandially)
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in viral genome up to Day 14
时间窗: Baseline and Day14
次要结局
- Pharmacokinetics: Mean Concentration of Pentarlandir™ UPPTA on Days 3, 7, 10, 14.(Day 3, 7, 10, and 14)
- Change from baseline in daily COVID-19-related symptom severity score through Day 28(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.(28 days)
- Number of days with progression (or worsening) of COVID-19-associated symptoms in ePRO through Day 28 compared to baseline.(Baseline to Day 28)
- Number of days with limited COVID-19-associated symptoms in ePRO from Day 1-28 based on self- assessment using daily ePRO symptom diary.(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.(28 days)
- Change from baseline in pulse oxygen saturation up to Day 14(Baseline to Day 14)
- Patient-reported global impression in ePRO(28 days)
- 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(28 days)
- Change from baseline in the patient's health status on a 7-category ordinal scale at up to Day 14(Baseline to Day 14)