A Trial in Participants With Chronic Obstructive Pulmonary Disease (COPD) to Evaluate the Impact of Vapendavir on the Development of Lower Respiratory Tract Symptoms Following Rhinovirus Challenge
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Peak change from baseline
研究概览
简要总结
Vapendavir (VPV) is a drug being developed to treat human rhinovirus (RV) infection, one virus responsible for the common cold. Vapendavir prevents the virus from entering cells and making more infectious copies of itself. A study is being planned to investigate VPV in patients with chronic obstructive pulmonary disease (COPD, a lung disease making it difficult to breathe) who develop a rhinoviral infection; however, VPV has not been approved for use in treating any indication (disease) by the FDA or any other global regulatory agency. Therefore, VPV is considered investigational, and the study doctor is conducting this investigational research study. Safety will be monitored throughout the entire study.
详细描述
Study Drug Indication:
- Treatment of HRV infections in patients with COPD
Study Rationale:
An effective, easily administered therapy for RV infection would have the potential to reduce the serious health effects in vulnerable populations, such as those with COPD. Treatment of RV infection could reduce the severity and frequency of acute COPD exacerbations, preserve pulmonary function, prevent secondary bacterial infections, and mitigate the need for costly medical interventions, including inhaled agents, steroids, antibacterial drugs, emergency treatment, hospitalization, and mechanical ventilation. Thus, early treatment of acute COPD exacerbations related to RV infection could potentially improve both the quality of life and longevity of COPD patients.
Altesa BioSciences, Inc. is developing drugs to treat RV and other respiratory virus infections. VPV has been shown to inhibit RV in vitro and in human clinical trials. Furthermore, VPV has been administered to more than 650 study participants and has been well-tolerated. Based on its potential to prevent severe respiratory complications, Altesa BioSciences, Inc is continuing the development of this drug for the treatment of RV infection.
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
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female age ≥40 years and ≤75 years at the time of signing the informed consent form.
- •If sexually active and/or of child-bearing potential (both females and males), must agree to use a highly effective forms of contraception ≥ 28 days prior to the first dose (females), during the study period (both males and females) and for 30 days (females) or 90 days (males) after the last dose. A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Highly effective contraception is defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly.
- •Males (including those with a vasectomy): agree to use a condom and if a female partner of childbearing potential, use of at least one other contraceptive method; males must also agree not to donate sperm within 90 days after the last dose).
- •WOCBP participants must use at least one highly effective contraceptive method.
- •Birth control methods which may be considered as highly effective:
- •Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
- •intravaginal
- •transdermal
- •progestogen-only hormonal contraception associated with inhibition of ovulation
- •injectable
- •implantable
- •intrauterine device (IUD)
- •intrauterine hormone-releasing system ( IUS)
- •bilateral tubal occlusion
- •vasectomised partner
- •Confirmed diagnosis of Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) stage II COPD as defined by % predicted Forced expiratory volume in 1 second (FEV1) ≥50% and FEV1/Forced vital capacity (FVC) <70%.
- •History of acute exacerbations of COPD as defined by the participant answering "yes" to the question "do your COPD symptoms get noticeably worse when you catch a cold?"
- •If on maintenance therapy, be medically stable for at least 2 months prior to enrolment.
- •Clinically stable with no exacerbations within 2 months prior to enrolment.
- •Ability to understand and give informed consent.
排除标准
- •Participants with other causes of chronic airflow limitation:
- •Including but not limited to: Asthma (mixed COPD and asthma is acceptable); cystic fibrosis (CF); bronchiolitis obliterans; and fibrosis such as tuberculosis (TB), idiopathic pulmonary fibrosis (IPF), or other major respiratory diagnosis (e.g., pneumonia, aspergillosis), etc.
- •Non-CF bronchiectasis
- •Any disorder, for example, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric impairment that is not medically stable, or other major physical impairment that is not considered by the investigator medically stable/controlled.
- •Prescription or over-the-counter medications or herbal products that could be impacted by CYP3A4 and CYP 2C19 induction or inhibition and have serious complications for the participant within the treatment period without the ability to discontinue safely with a sufficient washout period before initiating VPV.
- •Patients on oral contraceptives or estrogen containing hormone replacement therapy.
- •Ingestion of grapefruit, pomegranate, star fruit and Seville oranges within 14 days prior to dosing. The juices and products containing these fruits should also be avoided.
- •History of clinically significant infection (respiratory or non-respiratory) requiring antibiotic or systemic steroids >10 mg/day within 30 days prior to planned RV challenge.
- •Pregnant, planning to become pregnant, testing positive for pregnancy at the screening visit test, or nursing females during and within 30 days of treatment.
- •Any cold symptom within the last 6 weeks such as sore throat, sneezing, rhinorrhoea, malaise, nasal obstruction or cough.
- •Presence (at screening) of serum rhinovirus 16 neutralising antibody titers at greater than or equal to one in four (≥1/4) dilution.
- •Active allergic rhinitis, active nasal disease such as nasal polyposis, chronic rhinosinusitis etc.
- •Active alcohol and/or drug misuse, at the discretion of the Investigator.
- •Use of any over the counter cold prophylaxis products including nasal sprays, C-vitamins, zinc or Echinacea within 1 month prior to the enrolment.
- •Participation in other clinical trial with medical investigational product within 30 days or 5 drug half-lives (whichever is longer) prior to enrolment.
- •Hypersensitivity/allergy to any of the active or placebo ingredients/ components.
- •Individuals with close contact to at risk patient group, including:
- •Infants (less than 6 months);
- •The extremely elderly or infirm;
- •Pregnant and/or breastfeeding women;
- •Patients with immunosuppression (e.g., human immunodeficiency virus (HIV), transplant recipients on anti-rejection medications, those undergoing chemo- or immuno-therapy).
- •Other factors that in the opinion of the investigator are considered a risk.
研究组 & 干预措施
Vapendavir Cohort
VPV will be dispensed by the study team on Day 0 at the clinical study visit at the study site. Participants will be given enough VPV for the 7-day treatment phase, (eg. Days 2 to 8). Treatment is twice daily, am and pm, 12 h apart ± 2 h. VPV micronized free base tablets (250 mg each) will be given orally beginning with a 1,000 mg loading dose (4 tablets) as soon as symptoms are present or the subject answers "yes" to "do you think you have a cold today" followed by 500 mg (2 tablets) either on the same day (eg day 2) or the next day. Treatment will therefore be for a total of 7 days consisting of an initial 1,000 mg dose (4-tablets) followed by thirteen 500mg doses (2-tablets). Treatment may occur within the home, on non-clinical study days.
干预措施: Vapendavir (Drug)
Placebo Cohort
Placebo will be dispensed by the study team on Day 0 at the clinical visit at the study site. Participants will be given enough Placebo for the 7-day treatment phase, (eg. Days 2 to 8). Treatment is twice daily, am and pm, 12 h apart ± 2 h. Placebo tablets will be matched to the active treatment and will be administered orally for 7 days as follows: 4 tablets for the initial dose as soon as symptoms are present or the subject answers "yes" to "do you think you have a cold today" on the first day of dosing (eg. Day 2), and 2 tablets, either on the same day (eg Day 2) or the next day. Treatment will therefore be for a total of 7 days (consisting of an initial 4-tablet dose followed by thirteen 2-tablet doses). Treatment may occur within the home, on non-clinical study days.
干预措施: Placebo (Drug)
结局指标
主要结局
Peak change from baseline
时间窗: From Baseline Visit through Follow-Up Visit, up to 7 weeks
• Evaluation of the peak total lower respiratory symptom score (LRSS) in participants administered with VPV relative to/versus (vs) placebo as determined by Mallia et al (Am J Respir Crit Care Med. 2011) from day of treatment commencement until Day 42. This is a measure of a number of lower respiratory symptoms in a 24 hour period that include: shortness of breath (scale 0-4; 0 = not breathless, 4 = breathless at rest) wheeze (0-4; 0 = no wheeze, 4 = wheeze at rest), cough (0-3; 0 = no cough, 3 = severe cough), sputum quantity (0-3; 0 = none, 3 = large volume , more than 100 ml) sputum quality (0-3; 0 = none, 3 = purulent, green in colour). The total lower respiratory symptom score is the sum of all the above measurements (minimum 0, maximum 17) recorded on each day. These values will be recorded via a study diary over a six week period (day 0-42). Peak value is the highest daily total value over the 6 week post-infection period.
次要结局
- Peak Virus Load as measured in RNA copies per mL(Day of treatment commencement to Day 42)
- Peak Sputum Bacterial Load(Day of treatment commencement to Day 42)
- Maximum Change in Forced Expiratory Volume in 1 Second (FEV1)(Day of treatment commencement to Day 42)
- Peak Overall Symptom severity(Day of treatment commencement to Day 42)
- Maximum Change in Forced Vital Capacity(Day of treatment commencement to Day 42)
- Peak COPD Specific Respiratory Symptoms(Day of treatment commencement to Day 42)
- Peak Upper Respiratory Symptoms(Day of treatment commencement to Day 42)
- Maximum Change in FEV1/FVC(Day of treatment commencement to Day 42)