A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Multicenter Study to Evaluate the Efficacy and Safety of F-652 (IL-22:IgG2 Fusion Protein) in Patients With Moderate to Severe COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- NIAID 8-point Ordinal Scale
研究概览
简要总结
This is an interventional, multicenter, 2-arm, parallel-group, randomized, double-blind, placebo controlled, dose-escalation, safety and efficacy study of F-652 treatment versus placebo in patients aged 18 years or older with a COVID-19 diagnosis confirmed by PCR. Eligible patients will have moderate to severe COVID-19 symptoms within 5 days post hospitalization and a positive COVID-19 testing.
详细描述
The study is planned to include 4 cohorts, with enrolled patients being randomized 1:1 in a blinded manner on Day 1, following screening, to F-652 or placebo as follows:
- Cohort 1 (sentinel cohort): Four patients will receive either dose level 1 F-652 or placebo. Upon completion of sentinel, the Data Monitoring Committee will evaluate the safety and tolerability data of the sentinel patients and determine if it is acceptable to dose the remaining patients in this dosing group in Cohort 2.
- Cohort 2: Fourteen patients will receive either dose level 1 F-652 or placebo. Upon completion of Cohort 2, the DMC will convene and review all available safety data to determine if the study can proceed to the next dose level.
- Cohort 3 (sentinel cohort): Four patients will receive either dose level 2 F-652 or placebo. Upon completion of sentinel dosing, the DMC will evaluate the safety and tolerability data of the sentinel patients and determine if it is acceptable to dose the remaining patients in this dosing group in Cohort 4.
- Cohort 4: Sixteen patients will receive either dose level 2 F-652 or placebo. Treatment will begin on Day 1 following randomization. Patients assigned to active drug will receive a total of 2 doses of F-652 (1 IV infusion on Day 1 and 1 IV infusion on Day 8). Patients assigned to placebo will receive identical IV infusions of placebo vehicle on Days 1 and 8. All patients will receive available supportive and antiviral therapies as standard of care. Efficacy will be assessed on Days 15 and 29. Patients will be followed for safety until Day 60.
The primary efficacy endpoint is the proportion of patients with a ≥2-point increase in the National Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal scale from baseline to Day 29.
The secondary efficacy endpoints include the proportion of patients with a ≥2-point increase in the NIAID 8-point ordinal scale from baseline to Day 15, mortality rate by Days 15 and 29, percentage of patients who have recovered and discharged from the hospital by Days 15 and 29, and percentage of patients progressed to severe/critical disease by Day 15.
The safety endpoints include all cause treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs); change from screening (baseline) in clinical symptoms and abnormal vital signs, abnormal laboratory tests; and relationship of any AEs with F-652 treatment.
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)
盲法说明
Patients will be randomized in a 1:1 ratio in a double-blind manner to receive F-652 or placebo.
An independent statistician from Medpace will generate the randomization schedule. Patients meeting eligibility criteria will be randomized on Day 1 in a 1:1 ratio to F-652 or placebo, respectively. Patients will be assigned a randomization number and treatment assignment according to the randomization schedule. This randomization schedule will be maintained by the investigative site pharmacist until it is appropriate to break the blind. The Investigator, investigative site personnel (except site-designated pharmacist and dedicated assistant), study monitors, vendors, Sponsor, and Medpace will remain blinded to treatment assignment.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing to provide informed consent and able to comply with protocol requirements
- •18 years or older
- •Has a COVID-19 diagnosis confirmed by PCR
- •Hospitalized within 5 days and meets the following criteria at screening:
- •Peripheral capillary oxygen saturation (SpO2) ≤ 93% on room air or SpO2 ≥93% on ≤10 liters per minute of supplemental oxygen via nasal cannula
- •Radiographic (chest X-ray, computed tomography scan, or ultrasound) evidence of bilateral pulmonary infiltrates consistent with SARS-CoV-2/COVID-19
- •Clinical symptoms consistent with COVID-19 per Investigator judgement
- •Body mass index between 18 to 40 kg/m2
- •If of reproductive potential, willing to abstain or agree to the use of highly effective contraception
排除标准
- •Respiratory failure at screening
- •History of heart failure
- •History of COPD or bronchial asthma
- •Active TB or history of TB of the following types
- •Uncontrolled arrhythmia within 3 months prior to randomization
- •Heart disease of the following types
- •Moderate to severe renal insufficiency
- •Abnormal white cell and platelet counts
- •History of transplantation of vital organs (e.g., heart, lung, liver, and/or kidney);
- •Malignant tumor
- •Uncontrolled systemic or local autoimmune or inflammatory disease besides SARS-CoV-2
- •Unhealed wounds, active gastric ulcer, had surgery
- •Received other investigational therapeutic products
- •Used interferon therapies
- •History of HIV infection, hepatitis B, and/or hepatitis C
- •Known serious allergic reaction or hypersensitivity to components of F-652
- •Pregnant or breastfeeding
- •History of drug abuse or use of narcotics
- •Treated with immunomodulators or immunosuppressants
- •Other conditions resulting in increased risk
结局指标
主要结局
NIAID 8-point Ordinal Scale
时间窗: Study day 1 before dose to day 29
The proportion of patients with a greater or equal 2-point change in the National Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal scale from baseline to Day 29. The NIAID 8-point ordinal scale includes the following grades: 1. Death; 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; 3. Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplementation oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized, limitation on activities and/or requiring home oxygen; and 8. Not hospitalized, no limitations on activities.
次要结局
未报告次要终点