A Phase 2, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Leronlimab for Mild to Moderate Coronavirus Disease 2019 (COVID-19)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 12
- 主要终点
- Mean Change From Baseline in Total Symptom Score
研究概览
简要总结
This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection.
详细描述
This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection. Patients will be randomized to receive weekly doses of 700 mg leronlimab (PRO 140), or placebo. Leronlimab (PRO 140) and placebo will be administered via subcutaneous injection.
The study will have three phases: Screening Period, Treatment Period, and Follow-Up Period.
A total of 75 subjects will be randomized 2:1 in this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female adult ≥ 18 years of age at time of enrollment.
- •Subjects with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection as defined below:
- •Mild (uncomplicated) Illness:
- •Diagnosed with COVID-19 by a standardized RT-PCR assay AND
- •Mild symptoms, such as fever, rhinorrhea, mild cough, sore throat, malaise, headache, muscle pain, or malaise, but with no shortness of breath AND
- •No signs of a more serious lower airway disease AND
- •RR<20, HR <90, oxygen saturation (pulse oximetry) > 93% on room air
- •Moderate Illness:
- •Diagnosed with COVID-19 by a standardized RT-PCR assay AND
- •In addition to symptoms above, more significant lower respiratory symptoms, including shortness of breath (at rest or with exertion) OR
- •Signs of moderate pneumonia, including RR ≥ 20 but <30, HR ≥ 90 but less than 125, oxygen saturation (pulse oximetry) > 93% on room air AND
- •If available, lung infiltrates based on X-ray or CT scan < 50% present
- •Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator.
- •Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
- •Understands and agrees to comply with planned study procedures.
- •Women of childbearing potential must agree to use at least one medically accepted method of contraception (e.g., barrier contraceptives [condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], or intrauterine devices) for the duration of the study.
排除标准
- •Subjects showing signs of acute respiratory distress syndrome (ARDS) or respiratory failure necessitating mechanical ventilation at the time of screening;
- •History of severe chronic respiratory disease and requirement for long-term oxygen therapy;
- •Subjects showing signs of clinical jaundice at the time of screening;
- •History of moderate and severe liver disease (Child-Pugh score >12);
- •Subjects requiring Renal Replacement Therapy (RRT) at the time of screening;
- •History of severe chronic kidney disease or requiring dialysis;
- •Any uncontrolled active systemic infection requiring admission to an intensive care unit (ICU); Note: Subjects infected with chronic hepatitis B virus or hepatitis C virus will be eligible for the study if they have no signs of hepatic decompensation.
- •Note: Subjects infected with HIV-1 will be eligible for the study with undetectable viral load and are on a stable ART regimen. Investigators are required to review the subjects' medical records to confirm HIV-1 RNA suppression within the previous 3 months.
- •Note: Empirical antibiotic treatment for secondary bacterial infections is allowed during the course of study.
- •Patients with malignant tumor, or other serious systemic diseases;
- •Patients who are participating in other clinical trials;
- •Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible; and
- •Inability to provide informed consent or to comply with test requirements
研究组 & 干预措施
Placebo
The placebo comparator consists of the formulation buffer for leronlimab, i.e., the placebo is the same as the active arm without leronimab. The placebo is presented in the same container closure at the same fill volume as the active (nominal 1mL fill volume). The formulation buffer contains histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections.
干预措施: Placebo (Drug)
700mg Leronlimab
Each vial of active contains 175mg of leronlimab at a concentration of 175mg/ml (nominal 1mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections.
干预措施: Leronlimab (700mg) (Drug)
结局指标
主要结局
Mean Change From Baseline in Total Symptom Score
时间窗: Clinical Improvement will be assessed at baseline and at EOT (day 14).
Clinical Improvement as assessed by change in total symptom score (for fever, myalgia, dyspnea and cough) by count of patients showing improvement, no change or worsened. Note: The total score per patient ranges from 0 to 12 points. Each symptom is graded from 0 to 3. \[0=none, 1=mild, 2=moderate, and 3=severe\]. Higher scores mean a worse outcome. A negative change from baseline shows an improvement in symptom score.
次要结局
- Time to Clinical Resolution (TTCR)(Time (in days) from initiation of study treatment until resolution of clinical symptoms (fever, myalgia, dyspnea and cough).)
- Incidence of Hospitalization(From visit 2 (day 0) through day 14 (in days))
- Duration (Days) of Hospitalization(Total duration of hospitalization between visit 2 (day 0) in days and end of treatment)
- Incidence of Mechanical Ventilation(Total duration of mechanical ventilation since visit 2 (day 0) (days))
- Duration of Mechanical Ventilation Supply(Duration of mechanical ventilation since visit 2 (day 0) (days)
- Incidence of Oxygen Use(Use of oxygen since visit 2 (day 0) to end of treatment)
- Duration of Oxygen Use(Total duration of oxygen use since visit 2 (day 0) to EOT (day 14) (days))
- Mortality at Day 14(Mortality at EOT (day 14))
- Time to Return to Normal Activity(Date of first exposure to treatment to the first occurrence of ordinal scale equals "not hospitalized, no limitations of activities")
- Change From Baseline in National Early Warning Score 2 (NEWS2) to Day 3, 7 and 14(Baseline to Day 3, 7 and 14)
- Mean Change in Percent Oxygen Saturation From Baseline to Days 3, 7 and 14(Mean change in percent oxygen saturation from baseline to Days 3, 7 and 14)
- Change From Baseline in the Patient's Health Status on a 7-category Ordinal Scale on Days 3, 7 and 14(Assessments performed Day 0 (first treatment is Visit 2, day 0), Visit 3 (3+/- 1 day after first treatment) Visit 4 (second treatment, 7+/- 1 day from V2, day7) and end of treatment (7+/- 1 day from V4, day 14))