RESOLUTION: A Double-blind, Randomized, Placebo-controlled, Phase II/III Study of the Efficacy and Safety of LAU-7b in the Treatment of Adult Hospitalized Patients With COVID-19 Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 351
- 试验地点
- 29
- 主要终点
- Primary Outcome for Phase 2: Proportion of Participants Alive and Free of Respiratory Failure by Day 29 (Ordinal Scale Scores 1-4, Inclusively)
研究概览
简要总结
A randomized, double-blind, placebo-controlled Phase 2/3 Study of LAU-7b against confirmed COVID-19 Disease in hospitalized patients at a higher risk of complications.
详细描述
RESOLUTION is a multicenter, randomized, double-blind, placebo-controlled Phase 2/3 study of LAU-7b for the treatment of COVID-19 Disease in participants at a higher risk than the general COVID-19 Disease population to develop complications while hospitalized.
The goal of the study is to evaluate the efficacy of LAU-7b therapy + standard-of-care relative to placebo + standard-of-care in participants with COVID-19 Disease with confirmed SARS-CoV-2 infection. SARS is "severe acute respiratory syndrome". CoV is " Coronavirus".
The purpose of the treatment with LAU-7b is to prevent the worsening of the health of hospitalized participants including aggravation such as recourse to mechanical ventilation and death.
The means are the direct effects of LAU-7b on the resolution of inflammation, interference with viral proliferation and protection from excessive pro-inflammatory response.
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 randomly assigned to take either the active drug (LAU-7b capsule) or a matching inactive placebo (inactive capsule)
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
- •Participant exhibited symptoms [Extension Phase 3 study only: (including at least one lower respiratory symptom such as shortness of breath or dyspnea)] of COVID-19 disease at screening and/or since the start of their hospitalization (may have included treated symptoms)
- •Participant was 18 years and older, of either gender
- •Participant must have had at least one of the following factors/co-morbidities:
- •Controlled or uncontrolled diabetes
- •Pre-existing cardiovascular disease, including hypertension
- •Pre-existing respiratory disease such as chronic obstructive pulmonary disease(COPD), asthma, emphysema
- •Active [Extension Phase 3 study only: or a former smoker] with 20 pack-years of smoking history
- •Obesity as depicted by BMI ≥30 kg/m2
- •Laboratory tests indicative of a higher risk of COVID-19-related complications, such as troponin >1.5 the upper limit of normal (ULN), [Extension Phase 3 study only: D-dimer >3.0 ULN] and/or C reactive protein (CRP) >1.5 ULN
- •Aged 70 years and older who, based on the judgment of the investigator, was at a higher risk of developing complications
- •Participant had a documented positive test for the SARS-CoV-2 virus [Pilot Phase 2 study only: or was suspected to be positive and with a test result pending]. [Extension Phase 3 study only: Co-infection with other viral respiratory infections was allowed and had to be documented in medical history]
- •Participant was under observation by, or admitted to, a controlled facility or hospital [Extension Phase 3 study only: for no more than 48 hours (72 hours from amendment 3 onwards) before screening, including any prior stay in another hospital] to receive standard of care (SoC) for COVID-19 disease
- •[Pilot Phase 2 study only: Participant's hs was 3, 4, or 5 on the WHO ordinal scale and not previously a "6"] [Extension Phase 3 study only: 3 or 4 on the World Health Organization (WHO) ordinal scale and not previously a "5 or a 6"]
- •If female, participant was either post-menopausal (one year or greater without menses), surgically sterile, or, for female subjects of child-bearing potential who were capable of conception had to be practicing a highly effective method of birth control (acceptable methods included intrauterine device, complete abstinence, spermicide + barrier, male partner surgical sterilization, or hormonal contraception) during the study and through 30 days after the last dose of the study medication. Periodical abstinence was not classified as an effective method of birth control. A pregnancy test had to be negative at the Screening Visit
- •Participant had the ability to understand and give informed consent, which could have been verbal with a witness, according to local requirements
- •Participant was deemed capable of adequate compliance including attending scheduled visits for the duration of the study
- •Participant was able to swallow the study drug capsules
排除标准
- •Pregnancy or breastfeeding
- •Health condition deemed to possibly interfere with the study endpoints and/or the safety of the participants. For example, the following conditions were considered contraindicated for participation in the study, but this was not an exhaustive list. In case of doubt, the investigator was to consult with the Sponsor's medical representative:
- •Presence of inherited retinitis pigmentosa
- •Presence or history of liver failure (Child-Pugh B or C)
- •Presence or history of stage 4 severe chronic kidney disease or dialysis requirement
- •Febrile neutropenia
- •[Pilot Phase 2 study: Presence of active cancer treated with systemic chemotherapy or radiotherapy][Extension Phase 3 study: Presence of end-stage cancer]
- •Known history of a severe allergy or sensitivity to retinoids, or with known allergies to excipients in the oral capsule formulation used in the study
- •Participation in another drug clinical trial within 30 days (or a minimum of 5 t½) prior to screening, except ongoing participation in non-interventional studies
- •Calculated creatinine clearance (CrCl), using the Cockroft-Gault equation for example [Pilot Phase 2 study: <60 mL/min] [Extension Phase 3 study: <30 mL/min)]
- •Presence of total bilirubin >1.5 x ULN (in the absence of demonstrated Gilbert's syndrome), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2.5 x ULN
- •[Extension Phase 3 study only: Subject expected to be transferred to ICU or die in the next 24 hours]
研究组 & 干预措施
LAU-7b
Active drug as LAU-7b capsules
干预措施: LAU-7b (Drug)
Placebo
Placebo oral capsule (as inactive capsules identical to active arm)
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Primary Outcome for Phase 2: Proportion of Participants Alive and Free of Respiratory Failure by Day 29 (Ordinal Scale Scores 1-4, Inclusively)
时间窗: On Day 29
This will be assessed through health status scoring using the WHO 7-point Ordinal Scale, a higher score is worse than a low score. 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or extra-corporeal membrane oxygenation 7. Death
Primary Outcome for Phase 3: Proportion of Participants Requiring Mechanical Ventilation (Includes Extra-corporeal Membrane Oxygenation - ECMO) AND/OR Deceased (All Causes) by Day 60 (Ordinal Scale Scores 1-4, Inclusively)
时间窗: By Day 60
This will be assessed through health status scoring using the WHO 7-point Ordinal Scale, a higher score is worse than a low score. 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or extra-corporeal membrane oxygenation 7. Death
次要结局
- The Safety of LAU-7b Therapy, Overview.(From baseline to Day 60)
- The Safety of LAU-7b Therapy, Display of TEAEs With Incidence Equal or Greater Than 10% in Either Treatment Group(From baseline to Day 60)
- Health Status of the Participant on the 7-point Ordinal Scale on Days 14 and 29, Compared Between Active and Placebo Groups.(On Days 14 and 29)
- For Phase 2 Portion: Rate of All-causes Death by Day 29, Depicted by a Change From Baseline in the Ordinal Scale Score to Category 7(On Day 29)
- For Phase 3 Portion: Rate of All-causes Death by Day 29, Depicted by a Change From Baseline in the Ordinal Scale Score to Category 7(On Day 29)
- For Phase 2 Portion: Rate of All-causes Death By Day 60, Depicted by a Change From Baseline in the Ordinal Scale Score to Category 7(On Day 60)
- For Phase 3 Portion: Rate of All-causes Death By Day 60, Depicted by a Change From Baseline in the Ordinal Scale Score to Category 7(On Day 60)
- Proportion of Participants Alive and Free of Respiratory Failure by Day 29 (Ordinal Scale Scores 1-4, Inclusively)(Day 29)
- For Phase 2 Portion: Rate of COVID-19 Disease-related Aggravation, Depicted by a Change From Baseline in the Ordinal Scale Score of at Least One Category(From baseline to Day 60)
- For Phase 3 Portion: Rate of COVID-19 Disease-related Aggravation, Depicted by a Change From Baseline in the Ordinal Scale Score of at Least One Category(From baseline to Day 60)
- For Phase 2 Only: Rate of COVID-19 Disease-related Transfer to Intensive Care Unit, Depicted by a Change From Baseline in the Ordinal Scale Score to Categories 5 or 6.(From baseline to Day 60)
- For Phase 2 Only: Rate of COVID-19 Disease-related Transfer to Mechanical Ventilation, Depicted by a Change From Baseline in the Ordinal Scale Score to Category 6(From baseline to Day 60)
- For Phase 2 Only: Mean Change From Baseline of the Ordinal Scale Patient Health Status as a Function of Assessment Time.(From baseline to Day 60)
- For Phase 2 Only: Time to a Participant's Improvement of at Least One Category on the Ordinal Scale Health Status.(From baseline to Day 60)
- For Phase 2 Portion: Time to Recovery, Defined as the Time to Reach Categories 2 or 1 on the Ordinal Scale Participant Health Status (First Occurrence if More Than Once).(From baseline to Day 60)
- For Phase 3 Portion: Time to Recovery, Defined as the Time to Reach Categories 2 or 1 on the Ordinal Scale Participant Health Status (First Occurrence if More Than Once).(From baseline to Day 60)
- For Phase 2 Only: Time to Mechanical Ventilation, Defined Here as Time to Reach Category 6 on the Ordinal Scale Participant Health Status.(From baseline to Day 60)
- For Phase 2 Only: Time to Death, Defined Here as a Time to Reach Category 7 on the Ordinal Scale Participant Health Status, Censored to Day 60 if it Happens Later Than Day 60(From baseline to Day 60)
- For Phase 2 Portion: Duration of Hospitalization (Days) Within the Study Period Days 1-60(From baseline to Day 60)
- For Phase 3 Portion: Duration of Hospitalization (Days) Within the Study Period Days 1-60(From baseline to Day 60)
- For Phase 2 Only: Time to Attain an Undetectable Viral Load in Oropharyngeal Swabs.(Until discharge of participants, up to Day 60)
- The Change From Baseline in the Score Obtained on the EuroQol Five-dimensions Five-level (EQ-5D-5L) Quality-of-life Survey(On Days 1, 14, 29, 45 and 60)