A Parallel Treatment, Phase 2a, Double-blind, Randomized, Placebo-controlled, 4-arm Study to Evaluate the Safety, Tolerability, and Potential Efficacy of Intranasal AD17002 in Adult Aged 20 to 70 Years With Mild to Moderate COVID-19
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- The proportion of participants who experience adverse events
研究概览
简要总结
AD17002 has demonstrated superior safety and efficacy as a nasal adjuvant function to an influenza vaccine in two completed clinical studies, and has innate immune modulatory and anti-inflammatory properties which could potentially be an effective treatment for SARS-CoV-2 infection.
This Phase 2a, multi-center study is set up to assess the safety, tolerability, and potential efficacy of AD17002 in participants with mild to moderate COVID-19. The Immunogenicity of repeated doses of AD17002 will also be explored.
详细描述
AD17002 has demonstrated superior safety and efficacy as a nasal adjuvant function to an influenza vaccine in two completed clinical studies and has innate immune-modulatory and anti-inflammatory properties which could potentially be an effective treatment for SARS-CoV-2 infection.
This Phase 2a, multi-center study is set up to assess the safety, tolerability, and potential efficacy of AD17002 in participants with mild to moderate COVID-19. The cycle threshold (Ct) was used as a surrogate biomarker for viral clearance in the exploratory study.
The COVID-19 pandemic has led to significant mortality in global populations and suppression of the economy. The prompt development of the vaccine for SARS-CoV-2 represents an unprecedented achievement for mankind, nevertheless, the unstoppable transmission of the virus highlights human's insufficient and lack of preparedness in mucosal immunity, which acts as the port of entries to not just SARS-CoV-2, but many viruses.
The AD17002, also known as LTh(αK), is an immunomodulator, which induces expression of type I and III interferons (IFN-I/III) from mucosal epithelial cells. The IFN-I/III are critical components to innate immunity, the first line defender against infection, and modulator and initiator of adaptive immunity. The IFN-I is antagonized by many SARS-CoV-2 viral proteins and studies have shown the association between IFN-I deficiency and severe COVID-19. In this study, we intended to treat subjects with AD17002, which induced nasal epithelial cells to express IFN-I/III.
Participants who meet the eligibility criteria will be isolated and confined to the study site to receive treatment for COVID-19. Eligible participants will be assigned to 2 cohorts, Cohort 1 and Cohort 2, sequentially. Cohort 1 will receive 3 doses of AD17002 or placebo weekly, while Cohort 2 will receive 3 doses of LTh(αK) or placebo every other day (Days 1, 3, and 5). Within each cohort, participants will be randomized in a 2:1 ratio to receive standard-of-care treatment and add-on therapy of AD17002 at 20 μg or placebo. Randomized participants will be assigned a participant number. The participants, site personnel, and the Sponsor will be blinded to the treatment assignment. Randomization will not be stratified and participants who withdraw from the study after starting treatment will not be replaced, except for participants who undergo sentinel dosing in Cohort 2.
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)
入排标准
- 年龄范围
- 20 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged ≥ 20 and ≤ 70 years
- •SARS-CoV-2 infection confirmed by real-time RT-PCR ≤ 4 days before randomization.
- •Symptoms of mild to moderate illness with COVID-19 at Screening. At least one key COVID-19 symptom should have a score of 2 or higher using the scoring system in the diary card, with the exception of fever, sense of smell, and sense of taste where participants may be enrolled with a score of 1 or higher.
- •Have a negative serum pregnancy test at Screening (for female participants of childbearing potential). A female participant who is of childbearing potential agrees to remain abstinent or use (or have their partner use) two acceptable methods of birth control within the projected duration of the study. Acceptable methods of birth control are: intrauterine device, hormonal contraception, diaphragm with spermicide, contraceptive sponge, condom, vasectomy, as per local regulations or guidelines.
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5-fold of upper limit of normal (ULN) and total bilirubin ≤ 1.5-fold of ULN.
- •Creatinine clearance ≥ 50 mL/min.
- •A female participant who is not of childbearing potential is eligible without requiring the use of contraception. A female participant who is not of childbearing potential is defined as one who has either:
- •Reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone levels in the postmenopausal range as determined by the laboratory, or 12 months of spontaneous amenorrhea), or
- •At least six weeks postsurgical documented total hysterectomy and/or bilateral salpingo-oophorectomy, or
- •Bilateral tubal ligation
- •Participant or the participant's legal representative understands the study procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
- •Provide written informed consent for the study and willing to adhere to dose regimen and visit schedules.
排除标准
- •Participant has clinical signs suggestive of moderate (pneumonia) or more severe illnesses with COVID-19 (as defined in the Taiwan CDC "Interim Guideline for Clinical Management of SARS-CoV-2 Infection Version 13" (Taiwan CDC, Clinical Management of SARS-CoV-2 Infection).
- •Participation in any other clinical study of an investigational agent treatment for SARS- CoV-2 infection within 30 days prior to the first IMP dosing.
- •Participant who has a history of confirmed SARS-CoV-2 infection.
- •Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 < 24 hours prior to the first IMP dosing.
- •History of severe renal disease (treatment with dialysis or phosphate binders) or clinically apparent hepatic impairment (e.g., jaundice, cholestasis, hepatic synthetic impairment, active hepatitis).
- •Impaired cardiac function or clinically significant cardiac diseases as judged by the Investigator.
- •History of anaphylaxis reaction to any known or unknown cause.
- •Immunosuppressed persons as result of illness (e.g., HIV infection) or treatment.
- •Documented history of Bell's palsy.
- •History of allergic reaction to kanamycin.
- •Immunosuppressive treatment within 3 months prior to the Screening Visit.
- •Ongoing treatment with any specific immunotherapy at the time of the Screening Visit.
- •Assessed by the Investigator to be ineligible to participate in the study.
结局指标
主要结局
The proportion of participants who experience adverse events
时间窗: 7 weeks
Clinicians and Patients reported AEs in the study period (7 weeks)
The nasal tolerability to investigational medicinal products (IMPs)
时间窗: 7 weeks
Nasal symptoms will be assessed by participants and ear-nose-throat (ENT) specialists on symptoms include runny nose, stuffy nose, nasal discomfort, sneezing, lacrimation, change in vision, red eyes, facial swelling, nasal pain. Symptom Score Guide: 0= None; 1= Mild; 2= Moderately; 3= Severe
The proportion of participants with treatment-emergent adverse events (TEAE) leading to investigational medicinal products (IMPs) discontinuation
时间窗: 7 weeks
Measuring and recording the AEs caused by treatment.
次要结局
- The time to proportions of participants have a Ct≥30(7 weeks)
- Time to recovery* of sore throat (days)(7 weeks)
- Time to recovery* of cough (days(7 weeks)
- Time to recovery* of fatigue (days).(7 weeks)
- Time to recovery* of other symptoms (days)(7 weeks)
- The mean change from baseline to each specified time point on National Early Warning Score 2 (NEWS2)(7 weeks)
- Time to recovery* of fever (days)(7 weeks)
- Time to recovery* of muscle/body pain (days)(7 weeks)