A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Proof-Of-Concept Study To Evaluate Efficacy And Safety Of Recombinant Human Plasma Gelsolin (Rhu-pGSN) Added To Standard Of Care In Subjects With Severe Covid-19 Pneumonia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 3
- 主要终点
- Efficacy: Proportion of Subjects Alive Not on Vasopressors, Mechanical Ventilator, or Dialysis
研究概览
简要总结
Study Objectives:
Primary
- To assess the efficacy (survival without organ failure on Day 14) of three doses of rhu-pGSN administered intravenously (IV) plus standard of care (SOC) to hospitalized subjects with a primary diagnosis of COVID-19 pneumonia and a severity score of 4, 5 or 6 on the World Health Organization (WHO) 9-point severity scale
- To evaluate the safety and tolerability of three IV doses of rhu-pGSN administered to hospitalized subjects with a primary diagnosis of COVID-19 pneumonia and a severity score of 4, 5, or 6 on the WHO 9-point severity scale
Secondary
- To further assess the efficacy of IV administered rhu-pGSN
- To assess changes in WHO 9-point severity score for SOC with or without rhu-pGSN
- To evaluate the effect of administered rhu-pGSN on survival rates
- To assess the relationship of pGSN levels (and other biomarkers) at baseline with clinical outcomes
- [OPTIONAL] To follow the pharmacokinetics (PK) of administered rhu-pGSN
Immunogenicity
• To investigate the development of antibodies against rhu-pGSN post-treatment
详细描述
Efficacy and safety of IV rhu-pGSN on top of SOC will be evaluated initially in 60 participants representative of the drug target population: high-risk subjects with acute severe pneumonia due to COVID-19. The rhu-pGSN dose will be based on actual body weight given at 12 mg/kg. Three doses will be given at 0, 12 and 24 hours intervals promptly after enrollment by IV infusion through a 0.2 µm filter. Participants will be randomized 1:1 rhu-pGSN or placebo. Interim safety analyses will be conducted after enrollment of 12, 24, 36, and 48 patients.
The primary efficacy outcome will be the proportion of patients surviving on Day 14 without mechanical ventilation, vasopressors or dialysis. Secondary efficacy outcomes will include: daily change in 9-point WHO severity score through at least Day 14; all-cause mortality at Days 28 and 90; time to death (Kaplan-Meier survival analysis); proportion of subjects alive on Days 7, 28, 60, and 90 without: ongoing use of vasopressors, ongoing intubation/mechanical ventilation, ongoing residence in an intensive care unit (ICU), new ongoing need for dialysis/renal replacement therapy; proportion of subjects discharged to home or immediate prior residence by Day 28; days on the ventilator; length of stay in hospital and in ICU and re-admission to an acute-care hospital up to Day 90. Safety of administration of rhu-pGSN at the indicated dosage will also be evaluated.
Baseline and sequential levels of pGSN and inflammatory biomarkers will be measured. On days 1, 28, and 90, immunogenicity due to the formation of anti-pGSN antibodies will be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Treatment blinded to all but unblinded pharmacist
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
- •Hospitalized with laboratory-confirmed (RT-PCR+) or highly suspected (compatible with at least bilobar lung involvement without another plausible diagnosis) COVID-19
- •Weight ≤100 kg
- •Within 24 hours of reaching a WHO severity score of 4-6 either:
- •At admission
- •While already hospitalized
- •Informed consent obtained from subject/next of kin/legal proxy
- •Primary admitting diagnosis of pneumonia supported by a compatible clinical presentation with a documented infiltrate consistent with pneumonia on chest radiograph or CT as assessed by the admitting emergency-department (ED), clinic, or ward physician or equivalent caregiver
- •Recommended (not mandatory) guidance/discretionary criteria defining patients with pneumonia satisfying all 4 categories below:
- •At least 2 symptoms: difficulty breathing, cough, production of purulent sputum, or chest pain
- •At least 2 vital sign abnormalities: fever, tachycardia, or tachypnea (thresholds -- fever: oral or core temperature >100.4 °F [38 °C]; heart rate >100 beats/min; respiratory rate >24/min)
- •At least one finding of other clinical signs and laboratory abnormalities: hypoxemia (O2 saturation <90%), clinical evidence of pulmonary consolidation, or leukocytosis or leukopenia
- •Chest imaging or CT showing new (or presumed new or worsening) pulmonary infiltrates
- •Principal investigator to note radiologic findings in the electronic case report form (eCRF)
- •Radiology report to be placed in the eCRF
- •A copy of the radiograph attached to be saved for review
- •A hyperinflammatory status (defined by increased ferritin ≥500 µg/L, D-dimer ≥1000 ng/mL, or C-reactive protein (CRP) ≥75 mg/L)
- •During the course of the study starting at screening and for at least 6 months after their final study treatment:
- •Female subjects of childbearing potential must agree to use 2 medically accepted birth control methods
- •Male subjects with a partner who might become pregnant must agree to use reliable forms of contraception (i.e., vasectomy, abstinence), or an acceptable method of birth control must be used by the partner
- •All subjects must agree not to donate sperm or eggs (ovocytes)
排除标准
- •A negative RT-PCR test for COVID-19 during the evaluation of the present illness
- •Extracorporeal membrane oxygenation (ECMO)
- •Pregnant or lactating women
- •Active underlying cancer treated with systemic chemotherapy or radiation therapy during the last 30 days
- •Transplantation of hematopoietic or solid organs
- •Chronic mechanical ventilation or dialysis
- •Otherwise unsuitable for study participation because of chronic, severe, end-stage, and life-limiting underlying disease unrelated to COVID-19 likely to interfere with management and assessment of acute pneumonia, only comfort or limited (non-aggressive) care is to be given, or life expectancy <6 months unrelated to acute COVID infection in the opinion of the Investigator
研究组 & 干预措施
Placebo
Normal saline in matched volume to treatment arm. Undistinguishable in syringe.
干预措施: Placebo (Other)
Rhu-pGSN
Recombinant human plasma gelsolin reconstituted for slow bolus injection.
干预措施: Recombinant human plasma gelsolin (Rhu-pGSN) (Drug)
结局指标
主要结局
Efficacy: Proportion of Subjects Alive Not on Vasopressors, Mechanical Ventilator, or Dialysis
时间窗: Day 14
Number and percentage of subjects alive on Day 14 without ongoing use of vasopressors, ongoing intubation/mechanical ventilation, or new/ongoing need for dialysis/RRT. Subjects who discontinued from the study early or whose survival status was inconclusive on Day 14 were considered as a failure (Not Alive).
Safety: Number of Subjects With SAEs
时间窗: Day 1 through Day 90
Number of subjects with SAEs during the study
次要结局
- Efficacy: All Cause Mortality Rate at Day 90(Day 90)
- Number of Subjects Alive Without Organ Support at Day 90(Through Day 90)
- Safety and Tolerability: Proportion of Subjects With Adverse Events (AEs)(Continuous through Day 28)
- Immunogenicity: Subjects With Rhu-pGSN Antibodies(Day 28)
- Efficacy: Alive Without Support at Day 90(Day 90)
- Safety and Tolerability: Proportion of Subjects With Drug-related Adverse Events (AEs)(Continuous through Day 14)