A Phase IIa Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability and Efficacy of EIDD-2801 to Eliminate SARS-CoV-2RNA Detection in Persons With COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 204
- 试验地点
- 10
- 主要终点
- Number of Participants With Adverse Events (AEs) Grade 3 or Higher or Leading to Discontinuation of Study Treatment
研究概览
简要总结
This was a phase IIa, double-blind, placebo-controlled, randomized trial, designed to compare the safety, tolerability, and antiviral activity of EIDD-2801 (molnupiravir) versus placebo as measured by SARS-CoV-2 viral RNA detection in symptomatic adult outpatients with COVID-19.
详细描述
This was a phase IIa, double-blind, placebo-controlled, randomized trial, designed to compare the safety, tolerability, and antiviral activity of molnupiravir versus placebo as measured by SARS-CoV-2 viral RNA detection in symptomatic adult outpatients with COVID-19. The study was a multicenter trial that was conducted in the United States.
In this study, 204 participants were randomized and 202 received molnupiravir or placebo orally twice a day (BID) for 5 days. The study enrolled participants in 5 parts with each part evaluating molnupiravir doses of either 200 mg BID, 400 mg BID, or 800 mg BID. Doses were chosen based on emerging virology and safety data from this and ongoing studies. New dose groups were started after the selected dose had been studied for safety in a Phase 1 study.
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
- Double (Participant, Investigator)
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
- •Able to provide informed consent prior to initiation of any study procedures.
- •≥18 years of age at Screening.
- •Study treatment is expected to begin within ≤168 hours from first symptom onset.
- •Ability to swallow pills.
- •Documentation of confirmed active SARS-CoV-2 infection, as determined by a molecular or non-molecular ("rapid") test conducted at any clinic or laboratory that had a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent from a sample collected ≤96 hours prior to study entry.
- •Was experiencing at least one of the following SARS-CoV-2 infection symptoms at the time of enrollment: fever (could be subjective including feeling feverish or having chills) OR signs/symptoms of respiratory illness (including but not limited to upper respiratory congestion, loss of sense of smell or taste, sore throat OR lower respiratory illness - cough, shortness of breath).
- •Agreed to not participate in another interventional clinical trial for the treatment of SARS-CoV-2 during the study period (28 days) unless hospitalized.
- •Agreed to not obtain investigational medications outside of the molnupiravir study.
- •Agreed to the sampling detailed in the schedule of evaluations and to comply with study requirements including contraception requirements.
- •A female participant was eligible to participate if she was not pregnant or breastfeeding and at least one of the following conditions applied:
- •Was not a woman of childbearing potential (WOCBP) OR
- •Was a WOCBP and using a contraceptive method that is highly effective (a low user dependency method OR a user-dependent method in combination with a barrier method), or was abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 2 of the study protocol during the intervention period and for at least 50 days after the last dose of study intervention. The investigator evaluated the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
- •A WOCBP must have had a negative highly sensitive pregnancy test (serum or urine) within 24 hours before the first dose of study intervention.
- •Additional requirements for pregnancy testing during and after study intervention were provided in the study protocol.
- •The investigator was responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
- •Contraceptive use by women was to be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Given the elevated risk of venous thrombotic events in patients hospitalized with COVID-19 (Benson et al, 2020; Spratt et al, 2020), estrogen-containing contraceptives could not be started to fulfill the contraceptive requirement of this study at any time during participant's participation. If contraceptives were interrupted as standard of care management of COVID-19 patients and resumed at a later time point, such as at hospital discharge, then abstinence was practiced for the defined period of back-up contraception per the contraceptive product labeling. After this period, contraceptive use had to adhere to the guidance in Appendix 2 of the study protocol.
- •Male participants were eligible to participate if they agreed to the following during the intervention period and for at least 100 days after the last dose of study intervention:
- •Refrained from donating sperm
- •PLUS either:
- •Were abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agreed to remain abstinent.
- •Had to agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause [Appendix 2 of the study protocol]) as detailed below:
- •Agreed to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who was not pregnant. Note: Men with a pregnant or breastfeeding partner had to agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
- •Contraceptive use by men was to be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
排除标准
- •Need for hospitalization or immediate medical attention in the clinical opinion of the study investigator.
- •Hemoglobin <10 g/dL in men and <9 g/dL in women.
- •Platelet count <100,000/ µL or received a platelet transfusion within 5 days prior to enrollment.
- •Was on dialysis or has an estimated glomerular filtration rate <30 mL/min/1.73 m^2
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) >3x upper limit normal (ULN).
- •History of or current hospitalization for COVID-
- •Note: Individuals hospitalized and then discharged, even if only hospitalized for 1 day, were excluded.
- •History of kidney disease as evidenced by estimated creatinine clearance value <30 mL/min.
- •History of significant liver disease in the opinion of the site investigator or active hepatitis B or active hepatitis C. Human immunodeficiency virus (HIV) that is advanced (CD4<200/mm^3) and/or on treatment with nucleos(t)ide analogues.
- •Use of therapeutic interventions with possible anti-SARS-CoV-2 activity within 30 days prior to study entry, (e.g., remdesivir, lopinavir/ritonavir fixed dose combination, ribavirin, chloroquine, hydroxychloroquine, and convalescent plasma), or participation in a clinical trial involving any of these drugs whether for treatment or prophylaxis.
- •Receipt of a SARS-CoV-2 vaccination prior to study entry.
- •Known allergy/sensitivity or any hypersensitivity to components of molnupiravir, or its formulation.
- •Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- •History of recent (within the past 3 months) hemorrhagic cerebrovascular accident) or major bleed.
- •Presence of a condition, that in the opinion of the investigator, would place the subject at increased risk from study participation.
研究组 & 干预措施
Molnupiravir 200 mg
Molnupiravir 200 mg, twice daily (BID) for 5 days
干预措施: Molnupiravir 200 mg (Drug)
Molnupiravir 400 mg
Molnupiravir 400 mg, twice daily (BID) for 5 days
干预措施: Molnupiravir 400 mg (Drug)
Molnupiravir 800 mg
Molnupiravir 800 mg, twice daily (BID) for 5 days
干预措施: Molnupiravir 800 mg (Drug)
Placebo (PBO) twice daily (BID) for 5 days
干预措施: Placebo (PBO) (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs) Grade 3 or Higher or Leading to Discontinuation of Study Treatment
时间窗: 28 days
1) any AEs leading to early discontinuation of blinded treatment (active or placebo), 2) study drug-related discontinuation of treatment, 3) new grade 3 or higher AEs (not already present at baseline), and 4) study drug-related new grade 3 or higher AEs.
Number of Participants Until First Non-detectable SARS-CoV-2 in Nasopharyngeal (NP) Swabs
时间窗: 28 days
The number of participants until first non-detectable SARS-CoV-2 in nasopharyngeal (NP) swabs will be estimated for each randomized arm (drug versus placebo), using Kaplan-Meier methods with a corresponding log-rank test. Non detectable defined as "a viral load below the limit of quantification
Time to Clearance of SARS-CoV-2 in Nasopharyngeal Swabs
时间窗: 28 days
The distribution of days until first non-detectable SARS-CoV-2 in nasopharyngeal (NP) swabs will be estimated for each randomized arm (drug versus placebo), using Kaplan-Meier methods with a corresponding log-rank test. Non detectable defined as "a viral load below the limit of quantification
次要结局
- Number of Participants With Any Adverse Events (AEs), Grade 2 or Higher(28 days)