A Phase 2/3, Randomized, Double Blind, Placebo Controlled, Multicenter Study to Evaluate the Efficacy and Safety of FP-025 in Patients With Severe to Critical COVID 19 With Associated Acute Respiratory Distress Syndrome (ARDS)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 90
- 试验地点
- 8
- 主要终点
- The Percentage of Patients Alive and Not Requiring Non-invasive or Invasive Ventilation
研究概览
简要总结
This is a Phase 2/3, randomized, double blind, placebo controlled, multicenter study to evaluate the efficacy and safety of FP-025 in adult patients with severe to critical COVID 19 with associated ARDS.
详细描述
This is a Phase 2/3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of FP-025 in adult patients with severe to critical COVID-19 with associated ARDS. The patients in each phase (Phase 2 and Phase 3) will be analyzed separately. Each phase will consist of a Screening Visit, Treatment Period, and Follow-Up Period for a total study duration of approximately 60 days.
Phase 2: After eligibility is confirmed, approximately 90 patients will be randomized in a 1:1:1 ratio to receive FP-025 100 mg twice daily (BID), FP-025 300 mg BID, or placebo BID for 28 days. During Phase 2, randomized patients will be stratified by the use of invasive mechanical ventilation at the time of randomization (yes or no). At least one-third of patients should be on invasive mechanical ventilation to ensure that treatment benefits can be assessed for patients at different severity levels.
Patients with Grade 3 to Grade 4 heart failure, Stage 3 or greater chronic obstructive pulmonary disease, persistent asthma, and mild liver disease (ie, Child-Pugh Class A) will not be excluded from the study. The independent Data Monitoring Committee (iDMC) will independently monitor safety of the entire population and in different subgroups and may make recommendations as it deems appropriate. During Phase 2, no limitation in enrollment of subgroups is expected, unless clear safety signals arise in those subgroups during iDMC reviews.
The reason for hospital admission, the standard of care followed for each patient and center, and whether any care decisions were based on resource limitations will be clearly documented for all patients beginning on Day 1 (Visit 2). All patients will be allowed to receive standard of care and/or emergency use authorization (EUA) medications and treatment for COVID-19; however, the study drug should be discontinued for other non-standard of care concomitant medications used with the intent of directly treating COVID-19 unless there is prior Medical Monitor or Sponsor approval for the patient to remain on the study drug. If the use of concomitant medications necessitates study drug discontinuation, the patient should be encouraged to remain in the study and to follow-up for key study visits (Day 28 and Day 60) but will not be required to attend every study visit. If the patient withdraws, he/she should complete the Early Termination Visit.
Standard of care procedures for mechanical ventilation (eg, low tidal volume protective mechanical ventilation) and standard of care procedures for weaning from mechanical ventilation will be followed.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is willing to provide informed consent (or has a legally authorized representative [LAR] willing to provide informed consent) and is willing and able (or has an LAR willing and able) to comply with the protocol required therapy, monitoring, and follow-up;
- •Is a male or female aged ≥ 18 years;
- •Has a COVID-19 diagnosis confirmed by a documented, positive severe acute respiratory syndrome (SARS) CoV-2 reverse transcriptase polymerase chain reaction test (or equivalent test) immediately prior to or during the current hospitalization;
- •Is hospitalized with severe to critical COVID 19 within a 72-hour period prior to the Screening Visit and meeting the following characteristics:
- •Diagnosed with ARDS based on the Berlin criteria as follows:
- •Respiratory symptoms developed within 1 week of a known clinical insult or new or worsening respiratory symptoms developed during the past week;
- •Chest radiograph or computed tomography scan shows bilateral opacities not fully explained by pleural effusions, lobar or lung collapse, or pulmonary nodules; and
- •Respiratory failure is not fully explained by cardiac failure or fluid overload; and
- •Requiring at least 1 of the following:
- •Endotracheal intubation and mechanical ventilation;
- •Oxygen delivered by high flow nasal cannula (heated, humidified oxygen delivered via reinforced nasal cannula at flow rates > 20 L/minute with a fraction of delivered oxygen ≥ 0.5);
- •Non invasive positive pressure ventilation; or
- •Clinical diagnosis of respiratory failure (ie, the clinical need for 1 of the preceding therapies, but preceding therapies are unable to be administered in the setting of resource limitations);
- •If female, is post-menopausal for at least 1 year, surgically sterile (documented by medical record), or a woman of childbearing potential (WCBP) who agrees to use a highly effective method of birth control (ie, method with a failure rate < 1% per year) from enrollment until 30 days following the last dose of study drug. Highly effective methods of birth control are defined as follows: complete sexual abstinence, intrauterine device, intrauterine hormone-releasing system, progestogen-only hormonal contraception (implant, injectable, or oral), and combined (estrogen and progestogen) contraception (oral, intravaginal, or transdermal);
- •If a WCBP, must have a negative serum human chorionic gonadotropin pregnancy test at the Screening Visit, and must agree to monthly urine pregnancy tests during the study; and
- •If male, must be surgically sterile for at least 1 year prior to the Screening Visit (documented by medical record), or must agree to use a double barrier approach (eg, condoms with spermicide) during sexual intercourse between the Screening Visit and at least 90 days after administration of the last dose of study drug. Male patients must ensure that non pregnant female partners of childbearing potential comply with the contraception requirements in Inclusion Criterion 5.
排除标准
- •Is not expected to survive more than 24 hours;
- •Is on extracorporeal membrane oxygenation (ECMO) at the Screening Visit;
- •Has an underlying clinical condition where, in the opinion of the Investigator, it would be extremely unlikely that the patient would come off ventilation (eg, motor neuron disease, Duchenne muscular dystrophy, or rapidly progressive pulmonary fibrosis);
- •Has a known history of idiopathic pulmonary fibrosis or interstitial lung disease as defined by the American Thoracic Society 2018 guidelines;
- •Has known active tuberculosis (TB), a history of incompletely treated TB, and/or suspected or known extrapulmonary TB;
- •Has Child Pugh Class B or C active liver disease or an alanine aminotransferase or aspartate aminotransferase level > 4 x the upper limit of normal at the Screening Visit;
- •Has moderate to severe renal insufficiency, defined as an estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2, at the Screening Visit or requires hemodialysis;
- •Has a malignant tumor (excluding a malignant tumor cured with no recurrence in the past 5 years, completely resected basal cell and squamous cell carcinoma of skin, and/or completely resected carcinoma in situ of any type);
- •Has an uncontrolled systemic or local autoimmune or inflammatory disease besides COVID 19;
- •Has evidence of an active concurrent non COVID 19 pneumonia (requiring additional antimicrobial treatment) caused by a known or suspected bacterial pathogen, respiratory syncytial virus (RSV), influenza virus, SARS CoV 1, Middle East respiratory syndrome CoV, aspergillus, mucormycosis causing fungi, or other pulmonary pathogen(s);
- •Note: A viral respiratory panel will be administered at the Screening Visit to determine eligibility. At a minimum, the panel will evaluate for RSV, influenza A, and influenza B.
- •Has received any other investigational therapeutic products within 4 weeks or 5 half-lives, whichever is longer, prior to randomization;
- •Has a known history of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection;
- •Has a known serious allergic reaction or hypersensitivity to any components of FP-025;
- •Is pregnant or breastfeeding;
- •Has a history of drug or alcohol abuse within the past 2 years;
- •Is currently on another systemic immunomodulatory therapy that is not considered standard of care treatment for COVID 19 (eg, calcineurin inhibitor, hydroxychloroquine, anti cytokine therapy, or Janus kinase inhibitor); or Note: Corticosteroids, including dexamethasone, in doses used for standard of care treatment for COVID 19 are allowed.
- •Note: Corticosteroids that are being used for other indications are also allowed as long as the daily prednisone (or other corticosteroid equivalent) dose is ≤ 10 mg. Inhaled corticosteroids and nasal corticosteroids are also acceptable.
- •Note: As therapies for COVID-19 are rapidly evolving, other medications that may be considered standard of care can be considered with prior approval from the Sponsor or Medical Monitor.
- •Has any other condition that, in the opinion of the Investigator, could interfere with (or for which the treatment might interfere with) the conduct of the study or interpretation of the study results or that would place the patient at undue risk by participating in the study.
研究组 & 干预措施
FP-025 100 mg
Low dose for patient treatment.
干预措施: FP-025 100 mg (Drug)
FP-025 300 mg
High dose for patient treatment.
干预措施: FP-025 300 mg (Drug)
Placebo
Dose without any study drug, to make it a controlled study.
干预措施: Placebo (Drug)
结局指标
主要结局
The Percentage of Patients Alive and Not Requiring Non-invasive or Invasive Ventilation
时间窗: Day 28
Percentage of patients alive and not requiring non-invasive or invasive ventilation at Day 28
次要结局
- Percentage of Patients Alive(Day 60)
- Percentage of Patients on Invasive Mechanical Ventilation(Day 60)
- Percentage of Patients Alive and Not Requiring Non-invasive or Invasive Ventilation(Day 60)