A Prospective, Phase II Study to Evaluate Safety of 101-PGC-005 ('005) for Moderate to Severe COVID-19 Disease Along With Standard of Care
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 2.
研究概览
简要总结
In December 2019, a novel pneumonia caused by a previously unknown pathogen emerged in Wuhan, China. The pathogen was soon identified as a novel coronavirus (SARS-CoV-2), which is closely related to severe acute respiratory syndrome CoV (SARS-CoV) COVID-19, caused by the SARS-CoV-2 virus, leading to a major global public health threat. Many COVID-19 patients develop acute respiratory distress syndrome (ARDS) leading to death. The recent RECOVERY Trial demonstrated the success of dexamethasone in treating late-stage COVID-19 patients. However, use of dexamethasone increases mortality in the early stage of the disease, and dexamethasone is further limited because the therapeutic dose and duration is insufficient to safely and effectively treat most COVID-19 patients. As the majority of cells have glucocorticoid receptors to which dexamethasone binds, highly toxic doses would be needed to effectively treat COVID-19, which results in increased mortality as well as decreased natural immunity (via T-cell and other immune cell modulation). The investigational product 101-PGC-005 ('005) - a prodrug of dexamethasone that is targeted to only activated macrophages - will address the many safety and efficacy issues that limit dexamethasone. '005 can achieve much higher anti-inflammatory doses and avoid all undesirable immunosuppressive activities caused by standard dexamethasone administration, resulting in an even greater reduction in mortality among hospitalized patients and significantly reducing long term morbidity in patients who survive.
详细描述
This prospective Phase IIa study will evaluate the safety of '005 for moderate to severe COVID-19 disease along with Standard of Care (SOC) treatment. The Nineteen (19) eligible patients will be enrolled to receive '005 + SOC, 10 additional patients will be enrolled to a control group receiving the SOC together with placebo.
At the first open-label stage, 3+3+3 design will be implemented. Three (3) patients will be enrolled to receive 10mg '005 together with SOC, three (3) patients will receive 20mg'005 together with SOC, and three (3) patients will receive 30mg '005 together with SOC if no safety concerns are identified the second stage will be initiated.
At the second double blind stage neither the participants nor the investigator will know which treatment participants are receiving until the clinical trial is over [20 patients will be enrolled and randomly allocated in a 1:1 ratio to the treatment (SOC +'005) or placebo group (SOC + placebo)]. The treatment dose will be chosen based on the first stage safety results.
NOTE: '005 will be administered daily for three (3) consecutive days starting from the day of enrollment.
Standard of Care will be administered as long as required, per Investigator's judgment, institutional practice, or local, national, or international guidelines for COVID-19 management.
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
Double blind, neither the participants nor the investigator is aware of the assigned treatment.
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
- •Patients willing and able to provide voluntary written informed consent and to follow the protocol specific requirements.
- •Male or female patients over 18 years old.
- •Patients with positive RT-PCR test for SARS-CoV-2 in nasopharyngeal or oropharyngeal swabs (sample collected within 7 days prior to enrollment) who are admitted or being admitted to the hospital for a primary diagnosis of COVID-
- •In the case of female patients of child-bearing potential, a negative blood pregnancy test prior to beginning the therapy.
- •Patients intended to be hospitalized to receive SOC including dexamethasone treatment for COVID-19.
排除标准
- •Exclusion Criteria:
- •Patients with evidence of other serious infections.
- •Malignancy.
- •Background disease which, in the opinion of the investigator prevents the patient from participating in the study such as:
- •Presence of serious chronic infectious.
- •A condition resulting in immunodeficiency.
- •Participants with glucose levels upon admission ≥ 250 mg/dL
- •Acute psychosis
- •Patients in a critical stage of COVID-19 disease that require mechanical ventilation.
- •Pregnant and lactating women.
- •Patients that are currently or have participated in other clinical studies with investigational drug, biological agent, or device within 1 month or within 5 half-lives (of the drug/biologic) prior to enrollment (whichever is longer).
- •Patient currently receiving chemotherapy or immunosuppressive agents not including dexamethasone within 30 days before the screening.
研究组 & 干预措施
COVID-19 Patients
Moderate to severe COVID-19 patients receiving SOC and '005.
干预措施: 101-PGC-005 ('005) + SOC (Drug)
Control
Moderate to severe COVID-19 patients receiving SOC and placebo.
干预措施: Placebo + SOC (Drug)
结局指标
主要结局
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 2.
时间窗: At day 2
Evaluate the incidence of steroid-induced hyperglycemia Fasting Plasma Glucose (FPG).
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 3.
时间窗: At day 3
Evaluate the incidence of steroid-induced hyperglycemia Fasting Plasma Glucose (FPG).
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 10.
时间窗: At day 10
Evaluate the incidence of steroid-induced hyperglycemia Fasting Plasma Glucose (FPG).
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 4.
时间窗: At day 4
Evaluate the incidence of steroid-induced hyperglycemia Fasting Plasma Glucose (FPG).
次要结局
- To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 2.(At day 2)
- Changes from baseline in pro-inflammatory cytokines and Lymphocyte subtypes.(At day 10)
- Correlation with pro-inflammatory cytokines and change in COVID-19 symptoms(At day 10)
- Improvement of COVID-19 symptoms.(At day 10)
- Time to Saturation ≥94% on Room Air(At day 28)
- Blood evaluation for '005 PK.(At day 3: at baseline 30 min, 1, 2, 4, 5, 6, 8 and 24hr post dose)
- To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 3.(At day 3)
- To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 4.(At day 4)
- To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 10.(At day 10)
- To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.(At 28 days)
- The 28 days discharge rate.(At 28 days)
- COVID-19 severity improvement by MOH COVID-19 severity scale while in hospital, and at days 10 and 28 if discharged.(At 28 days)
- Reduction in inflammatory blood markers.(At 28 days)