Efficacy and safety of ES16001 in patients with COVID-19: a phase II/III, multinational, randomized, parallel-group, double-blind, placebo-controlled study
试验速览
- 阶段
- 2/3 期
- 状态
- 尚未招募
- 入组人数
- 1,130
- 试验地点
- 5
- 主要终点
- Primary Efficacy endpoint
研究概览
简要总结
Thisis phase II/III, randomized, parallel-group, double-blind, placebo-controlledstudy. Patients must be at least 19 years of age (or according to the legal agefor adult in each country) with confirmed mild or moderate COVID-19 testedpositive with an RT-PCR analysis of rhinopharynx samples. RT-PCR analysis ofrhinopharynx samples must be <4 days old prior to the studyenrolment.
After obtaining the consent and confirming eligibility, eligible patients will be treatedwith IMP for 7 days and followed up for additional 21 days (total 29days). Patients who are discharged from the hospital or ending the quarantine may have to visit the investigationalsite on a pre-determined date for efficacy and safety follow up observation.Final safety and efficacy data will be collected on the last study day (29t Day).
If patients are fully recovered or discharged fromthe hospital prior to treatment period, all the evaluations on the day/End ofTreatment examination treatment shall be performed on the day of discharging.
Criteria of discharge from quarantined facility orhospital will be granted when fulfilling the following conditions:
â‘ At least 10days after the first symptom
â‘¡ No fever for 24 hourswithout using an antipyretic drug
â‘¢ Other symptomsare improved
Treatment with IMP shall be suspended in case of patientsdischarged prior to the treatment completion, a follow up assessment will be performedon Study days 10, 14 and 21. The final study visit will beperformed at the site on Day 29. During these visits, efficacy, and safety data (adverse events) will be collected.
Should the patient’s conditions not improve during the treatment period(until Day 7), the study treatment will be considered a failure anddiscontinued. The patient will be managed as per local practiceand followed up until Day 29 for the safetyevaluation.
In case of a home quarantine or home isolated patients,field study personnel will travel in vans or cars equipped for transportationof NP swabs and blood samples. All study personnel and supporting staff (e.g.drivers) will use adequate personal protection equipment (PPE) for COVID-19 incompliance with local regulations. Vehicles will be sanitized in compliancewith local regulations.
Phase II —Dose-finding
PhaseII will be enrolled 424 patients (1:1:1:1 ratio) randomly assigned to one ofthe four treatment groups as follows.
· ES16001480 mg /day
· ES16001720 mg /day
· ES16001960 mg /day
· Placebo
Randomizationwill be stratified depending on age and disease severity of patients.
When the phase II clinical study will be completed, theassessment to select the dose will be performed in an unblinded manner by anIndependent Data Monitoring Committee (IDMC). An IDMC charter will be draftedto describe the IDMC’s activities and responsibilities. dose
PhaseIII
In the phase III, safety andefficacy with the dose selected in the phase II will be compared with placebo.In the phase III, about 706 patients will be randomized in 1:1 ratio to testdrug or placebo. Randomization will be stratified depending on the well-knownrisk factors for progression and disease severity of a patient. Final Endpointsand the sample size may be different depending on the results of the phase II.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Those with full understanding of the clinical study and agreeing in the participation of the clinical study voluntarily in writing, or with a deputy granted with legal authority of the relevant patient if he/she is unable to agree with the clinical study in person 2.Adults aged 18 or above at the time of screening (according to the legal age for adult in each country 3.Diagnosis of COVID-19 including a positive RT-PCR for SARS-CoV-2 within 3 days prior to administering the IMP 4.Mild or moderate patients who have the following conditions at screening and confirm at randomization: A.Mild: Those with COVID-19 symptoms relevant to the inclusion criteria 5 without breathing difficulty or other chest radiation examination B.Moderate: Those with disease in respiratory organs in the clinical evaluation or imaging examination (chest radiation examination, etc.) and also relevant to the following conditions: Higher than 94% of oxygen saturation (SpO2) with room air at screening and confirm at randomization Lower than 30 times/min respitatory frequency at screening 5.Those who happen more than one of the following symptoms within 3 days prior to the treatment of IMP and also have more than one of symptoms within a day prior to the treatment of IMP 1.Fever 2.Cough 3.Shortness of breath 4.Chills 5.Muscle pain’ 6.Headache 7.Sore throat 8.Loss of smell/taste 9.Nasal congestion 10.Runny nose 11.Fatigue 12.Nausea and vomiting 13.Diarrhea 14.Phlegm 6.Those being hospitalized or scheduled in hospital or quarantined facilities 7.Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use adequate methods of contraception during the study and through 90 days after the last dose of study medication.
- •Female patients of childbearing potential are all those except patients who are surgically sterile, who have medically documented ovarian failure, or who are at least 1 year postmenopausal.
- •Effective contraception includes an established hormonal therapy or intrauterine device for females, and the use of a barrier contraceptive (i.e. diaphragm or condoms) with spermicide.
排除标准
- •1.Those with known or suspected hypersensitivity to ES16001 or any of its excipients 2.Those with genetic issues with galactose intolerance, lapp lactase deficiency, or glucose-galactose malasorption, etc 3.Patients with ECG evidence of a QTcF > 450 ms in men and > 470 ms in women and patients with any other risk factors for Torsades de pointes (TdP) (hypokalemia, hypomagnesemia or hypocalcemia, family history of long QT syndrome, low left ventricular ejection fraction, left ventricular hypertrophy, ischemia and slow heart rate) 4.Concomitant use of hydroxychloroquine or other drugs known to prolong QT interval throughout the study 5.Suspected active bacterial, fungal, viral, or other infection (besides COVID-19).
- •6.Immunosuppressor or immunomodulatory drugs within the past 3 months (excluding corticosteroids) and patients with autoimmune disease 7.Patients with one of the following severe COVID-19 signs at randomization (based on NIH classification) SpO2<94% of oxygen saturation without oxygen supply in room air PaO2/FiO2<300 mmHg Respiratory frequency >30 times/min Parenchyma infiltration> 50% 8.Patients requiring oxygen treatment (nasal prong, facial mask, and high flow oxygen) or machine respiration (oxygen by NIV or high flow, intubation and mechanical ventilation, and etc.) at randomization 9.Those requiring ECMO or CRRT treatment due to damage on multiple organs with severe illness (respiratory failure, shock, or multiple organ disorder) 10.Those with issues on kidney or liver as follows in the screening 1) ALT or AST > 5 x upper limit of normal (ULN) at screening 2)Total bilirubin that is 1.5 x upper limit of normal (ULN) at screening in the blood 3) Serum creatine > 2mg/dL (> 176.8 μmol/L) or estimated creatine clearance < 30ml/min measured or calculated by Cockroft Gault equation
- •ANC <1000/µL in the screening 11.platelet count <50,000/µL in the screening 12.Those who are pregnant or breastfeeding 13.Treatment with an investigational product within 5 times half-life or to 30 days from the screening (whichever is longer) 14.Those taking antiviral drugs, anti-inflammatory medicine, or neutralizing antibody that is known to influence the treatment of COVID-19 (refer to 7.4.2 Prohibited mendication) Those with chronic disease that is inappropriate for the participation in clinical study judged by the investigator (Uncontrolled diabetes, chronic kidney disease, chronic liver disease, chronic lung disease, chronic cardiovascular disease, blood cancer, chemotherapeutic cancer patients, patients taking immunosuppressants, idiopathic thrombocytopenia, hyperkalemia patients, etc.).
结局指标
主要结局
Primary Efficacy endpoint
时间窗: Approximately 5 Weeks
次要结局
- Secondary endpoint:(•Proportion of subjects requiring hospitalization due to COVID-19 or dead subjects up to the 29th day treatment)