A Randomized, Double-blind, Placebo-controlled, Phase 2 Study to Evaluate the Efficacy and Safety of oral RP7214, a DHODH inhibitor, in Patients with Symptomatic Mild SARS-CoV-2 Infection.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 204
- 试验地点
- 17
- 主要终点
- Proportion of patients requiring Covid-19 related hospitalization by Day 15
研究概览
简要总结
| RP7214, a novel, potent, oral, inhibitor of DHODH, has shown preclinical evidence in inhibiting viral replication and lung inflammation. |
This was a randomized, double-blind, placebo-controlled phase 2 study in patients with symptomatic mild SARS-CoV-2 infection, having at least one high-risk feature (e.g., hypertension, diabetes mellitus) for developing severe Covid-19 infection. The patients received RP7214 (400 mg BID) or a placebo for 14 days in a blinded fashion and were followed up to 30 days. Patients also received supportive therapy (e.g., antipyretics and antitussives for symptomatic relief) at the discretion of the investigator. The endpoints were Covid 19 related hospitalization rate by Day 15, SARS-CoV-2 viral load and clearance on Days 3,7 and 15, clinical symptoms improvement by Day 15, safety, and the immuno-modulatory effect of RP7214.
A total of 163 patients were treated in the study; 82 received RP7214 and 81 received placebo. Of the total patients, 44.2% had received Covid-19 vaccine prior to the study. The symptom onset was ≤ 3 days in 22.1%. None of the patients in the study required hospitalization. There was no difference in the mean change of viral load between RP7214 and placebo. In the subgroup analysis, in patients having symptom onset of ≤ 3 days, RP7214 significantly reduced viral load on Days 3 and 7, respectively. Similarly, in non-vaccinated patients with symptom onset of ≤ 3 days, RP7214 significantly reduced viral load on Day 3. Overall, there was a trend towards better viral load reduction in RP7214-treated patients with a baseline viral load of 5 log units or higher. For all other endpoints, there was no difference between RP7214 and placebo. Majority of the reported AEs were mild and not related either to study treatment.
RP7214 at 400 mg BID dose level showed a statistically significant reduction in viral load at an early stage of the disease and in non-vaccinated patients. There was a trend towards better viral load reduction in RP7214-treated patients with a baseline viral load of 5 log units or higher. RP7214 showed a favorable safety profile. Further development of RP7214 in Covid 19 in a mild symptomatic population with co-morbidities and treated at an early stage of disease may show benefit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Willing and able to provide informed consent.
- •2.Males and females of ≥ 18 years of age, at the time of signing the informed consent.
- •3.Patient with mild COVID-19 infection having ≥ 1 symptoms.
- •Mild infection is defined as presence of any one of the signs and symptoms of COVID-19 such as fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and/or smell, without shortness of breath or hypoxia.
- •The respiratory rate should be < 24/min and SpO2 ≥ 94% on room air.
- •4.Laboratory confirmed Covid-19 infection by Reverse Transcription Polymerase Chain Reaction (RT-PCR) in nasopharyngeal sample (within 72 hours prior to randomization).
- •Patient should have at least one pre-existing high-risk feature (e.g., age> 60 years, hypertension, diabetes mellitus, chronic lung disease, chronic kidney disease, liver disease, cerebrovascular disease, obesity (Body mass index (BMI) > 30.0 kg/m2), cancer) for developing severe Covid-19 illness.
- •Male patient who is surgically sterile, or who is willing to agree to remain completely abstinent or will agree to use barrier contraceptive measures and agrees to refrain from donating sperm during the entire study treatment period and for 3 months after the last dose of study drug.
- •Women of childbearing potential who should be willing to use a medically acceptable method of contraception as defined in Appendix B while participating in the study and for 30 days after the last dose of study drug AND must have a negative pregnancy test within 3 days prior to dosing on Day
- •Willing to receive telephone calls or have videoconferences with study team personnel.
- •Willing and able to understand the nature of this study, comply with the study procedures and follow-up procedures as per the study protocol.
排除标准
- •Individuals who meet any of the following criteria will be considered ineligible to participate in the study:
- •Patient with asymptomatic Covid-19 infection.
- •Patient who has experienced onset of any of Covid-19 symptoms > 5 days at the time of randomization.
- •Moderate to Severe COVID-19 infection.
- •Moderate infection is defined as patients with pneumonia with no signs of severe disease.
- •Clinical features suggestive of presence of dyspnea and/or hypoxia, fever, cough, including SpO2 ≤ 93% (range 90-93%) on room air OR respiratory rate ≥ 24 per minute.
- •Severe infection is defined as patients with either severe pneumonia, acute respiratory distress syndrome, sepsis or septic shock.
- •Clinical features suggestive of clinical signs of pneumonia plus one of the following parameters such as respiratory rate > 30 breaths/min, severe respiratory distress and SpO2 < 90% on room air; or signs of acute respiratory distress syndrome or sepsis or septic shock.
- •Subjects who are severely immunocompromised (e.g., subjects with HIV infection, subjects with solid organ transplantation or bone marrow transplantation, subjects receiving chemotherapy/ radiotherapy, subjects with primary immunodeficiency).
- •Autoimmune diseases such as multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA).
- •Patients with any bleeding disorder e.g., hemophilia and von Willebrand disease.
- •Patients who are on or immediately require Covid-19 directed treatment such as antivirals (e.g., remdesivir, favipiravir), immunomodulatory treatment (e.g., tocilizumab, itolizumab, baricitinib or JAK inhibitors), convalescent plasma, oral/ intravenous steroids, or monoclonal antibodies at the time of screening.
- •Patients participating in another clinical study or use of any investigational product within 4 weeks or 5 half-lives of the drug, whichever is longer, before the date of dosing.
- •Patient with history of heart failure, Class 2 or greater using the New York Heart Association (NYHA) functional class.
- •Patients on medication that is associated with prolonged QT such as antipsychotic medications or antidepressants (e.g., citalopram, venlafaxine, and bupropion) and unable to stop the same during the trial.
- •Pregnant or lactating females.
- •Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient.
- •Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
- •Concurrent condition that in the investigator’s opinion would jeopardize compliance with the protocol.
结局指标
主要结局
Proportion of patients requiring Covid-19 related hospitalization by Day 15
时间窗: 15 Days
次要结局
- Change from baseline in SARS-CoV-2 viral load(Days 3, 7 and 15)
- Change in the disease specific inflammatory markers(Days 3, 7 and 15 as compared to baseline)
- Time to symptom resolution and improvement in patients receiving RP7214 as compared to placebo.(Day 1 to Day 15)
- Proportion of patients demonstrating symptom resolution
- Adverse Events (AEs) as assessed by laboratory tests, vital signs and physical examination.(Day 1 to 30)
- Effect of RP7214 on SARS-CoV-2 viral load and clearance in patients with mild SARS-CoV-2 infection as compared to placebo.(Effect of RP7214 on clinical symptoms)