NCT03960580已完成3 期
A 24-Week Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study Evaluating the Efficacy and Safety of Intranasal Administration of 186 and 372 μg of OPN-375 Twice a Day (BID) in Subjects With Chronic Rhinosinusitis Without the Presence of Nasal Polyps
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 223
- 试验地点
- 87
- 主要终点
- Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) at the End of Week 4
研究概览
简要总结
This is a 24-week randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the efficacy and safety of intranasal administration of 186 and 372 μg twice daily (BID) of OPN-375 in subjects with chronic Rhinosinusitis (CRS) without nasal polyps
详细描述
The primary objective of this study is to compare the efficacy of intranasal administration of twice-daily doses of 186 and 372 µg of OPN-375 (fluticasone propionate) with placebo in subjects with chronic rhinosinusitis using the following co-primary endpoints:
- A change from baseline in symptoms as measured by the average morning composite score of nasal congestion, facial pain or pressure sensation, and nasal discharge (anterior and/or posterior) at the end of Week 4.
- A change from baseline to Week 24/Early Termination (ET) in the average percent of the volume opacified in the ethmoid and maxillary sinuses.
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
- •men or women aged 18 years and older at baseline visit
- •women of child bearing potential must be abstinent, or if sexually active,
- •be practicing an effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method [eg, condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel], or male partner sterilization) before entry and throughout the study, or
- •be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or
- •be postmenopausal (amenorrhea for at least 1 year)
- •women of child-bearing potential must have a negative urine pregnancy test at Visit 1 (Screening)
- •must have a history of chronic sinusitis and be currently experiencing 2 or more of the following symptoms, 1 of which has to be either nasal congestion or nasal discharge (anterior and/or posterior nasal discharge) for equal to or greater than 12 weeks:
- •nasal congestion
- •nasal discharge (anterior and/or posterior nasal discharge)
- •facial pain or pressure
- •reduction or loss of smell
- •endoscopic evidence of nasal mucosal disease, with edema or purulent discharge; or polyps/polypoid tissue <Grade 1 in middle meatus, bilaterally
- •must have confirmatory evidence via a computed tomography(CT) scan of bilateral sinus disease (have at least 1 sinus on each side of nose with a Lund-Mackay score of ≥1)
- •baseline CT scan must show a combined ≥25% opacification of the ethmoid sinuses and ≥25% opacification of at least 1 maxillary sinus
- •must have at least moderate symptoms (as defined in protocol) of nasal congestion as reported by the subject, on average, for the 7-day period preceding Visit 1 (Screening) run-in
- •must have an average morning score of at least 1.5 for congestion on the Nasal Symptom Scale (as defined in protocol) recorded on the subject diary over a 7-day period during the first 14 days of the single-blind run-in period
- •must demonstrate an ability to correctly complete the daily diary during the run-in period to be eligible for randomization
- •Subjects with comorbid asthma or chronic obstructive pulmonary disorder (COPD) must be stable with no exacerbations (eg, no emergency room visits, hospitalizations, or oral or parenteral steroid use) within the 3 months before Visit 1 (Screening). Inhaled corticosteroid use must be limited to stable doses of no more than 1,000 μg/day of beclomethasone (or equivalent) for at least 3 months before Visit 1 (Screening) with plans to continue use throughout the study.
- •Subjects with aspirin-exacerbated respiratory disease, who have undergone aspirin desensitization and are receiving daily aspirin therapy, must be receiving therapy for at least 6 months prior to Visit
- •must be able to cease treatment with intranasal steroids, inhaled corticosteroids (except permitted doses listed above for asthma and COPD) at the screening visit.
- •must be able to cease treatment with oral and nasal decongestants and antihistamines at Visit 1 (Screening)
- •must be able to use the exhalation delivery system correctly; all subjects will be required to demonstrate correct use with the practice exhalation delivery system (EDS) at Visit 1 (Screening).
- •must be capable, in the opinion of the investigator, of providing informed consent to participate in the study. Subjects must sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
排除标准
- •women who are pregnant or lactating
- •inability to have each nasal cavity examined for any reason, including nasal septum deviation
- •inability to achieve bilateral nasal airflow
- •is currently taking XHANCE®
- •have previously used XHANCE® for more than 1 month and did not achieve an adequate symptomatic response
- •the nasal/sinus anatomy prevents the accurate assessment of sinus volume via CT scan
- •history of sinus or nasal surgery within 6 months before Visit 1 or has not healed from a prior sinus or nasal surgery
- •have current evidence of odontogenic sinusitis, sinus mucocele (the affected sinus is completely opacified and either the margins are expanded and/or thinned OR there are areas of complete bone resorption resulting in bony defect and extension of the "mass" into adjacent tissues), evidence of allergic fungal sinusitis, or evidence of complicated sinus disease (including, but not limited to, extension of inflammation outside of the sinuses and nasal cavity)
- •have a paranasal sinus or nasal tumor
- •have polyp grade ≥1 (polyp that is free on 5 sides and has a stalk) on either side of the nose as determined by the nasoendoscopy at screening
- •have a nasal septum perforation
- •have had more than 1 episode of epistaxis with frank bleeding in the month before Visit 1 (Screening)
- •have evidence of significant mucosal injury, ulceration (eg, exposed cartilage) on Visit 1 (Screening) nasal examination/nasoendoscopy
- •have current, ongoing rhinitis medicamentosa (rebound rhinitis)
- •have significant oral structural abnormalities (eg, a cleft palate)
- •have a diagnosis of cystic fibrosis
- •history of Churg-Strauss syndrome or dyskinetic ciliary syndromes
- •symptom resolution or last dose of antibiotics for purulent nasal infection, acute sinusitis, or upper respiratory tract infection has not occurred before Visit 1 or was less than 4 weeks before the CT scan. Potential subjects presenting with any of these infections may be rescreened 4 weeks after symptom resolution.
- •planned sinonasal surgery during the period of the study
- •allergy, hypersensitivity, or contraindication to corticosteroids or steroids
- •has used oral steroids in the past for treatment of chronic sinusitis and did not experience any relief of symptoms
- •has a steroid eluting sinus stent still in place within 30 days of Visit 1
- •allergy or hypersensitivity to any excipients in study drug
- •exposure to any glucocorticoid treatment with potential for systemic effects (eg, oral, parenteral, intraarticular, or epidural steroids, high dose topical steroids) within 1 month before Visit 1 (Screening); except as noted in inclusion criteria for subjects with comorbid asthma or COPD
- •have nasal candidiasis
- •history or current diagnosis of any form of glaucoma or ocular hypertension
- •history of intraocular pressure elevation on any form of steroid therapy
- •history or current diagnosis of the presence (in either eye) of a subcapsular cataract
- •history of immunodeficiency
- •any serious or unstable concurrent disease, psychiatric disorder, or any significant condition that, in the opinion of the investigator could confound the results of the study or could interfere with the subject's participation or compliance in the study
- •have a positive drug screen or a recent (within 1 year of Visit 1 [Screening]) history of drug or alcohol abuse, or dependence that, in the opinion of the investigator could interfere with the subject's participation or compliance in the study
- •have participated in an investigational drug clinical trial within 30 days of Visit 1 (Screening)
- •have received mepolizumab (Nucala®), reslizumab (Cinquair®), dupilumab (Dupixent®), omalizumab (Xolair®), or benralizumab (Fasenra™) within 6 months of Visit 1 (Screening)
- •is using strong cytochrome P450 3A4 (CYP3A4) inhibitors (eg, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, voriconazole)
- •is an employee of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, or is a family member of the employee or the investigator.
- •patients who report unexplained worsening of vision within the past 3 months (e.g. difficulty reading or seeing traffic signs from a distance). A diagnosis of presbyopia established by an eye care professional is not exclusionary.
研究组 & 干预措施
OPN-375 186 μg BID
Active Comparator
OPN-375 186 μg BID x 24 Weeks
干预措施: OPN-375 (Drug)
OPN-375 372 μg BID
Active Comparator
OPN-375 372 μg BID x 24 Weeks
干预措施: OPN-375 (Drug)
Placebo
Placebo Comparator
Matching Placebo BID x 24 Weeks
干预措施: OPN-375 (Drug)
结局指标
主要结局
Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) at the End of Week 4
时间窗: 4 Weeks
Change from baseline to the end of Week 4 in average total instantaneous AM scores (evaluation of symptom severity immediately preceding the time of scoring) for each symptom: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation. Baseline scores are the averaged total instantaneous AM scores over the last 7 days of the single blind run in period, and the end of Week 4, scores are averaged over the 7 days from the subject diary. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. Composite score is a sum of the 3 symptom scores and will range from 0 to 9.
Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified (APOV) in the Ethmoid and Maxillary Sinuses.
时间窗: Baseline, Week 24
Change from baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT. Percent volume opacified can range from 0% to 100%. Outcome measure is the percentage change from percent opacification at baseline to percent opacification at Week 24; therefore, change in opacification volume can range from -100% to 100%. For example, if Baseline opacification was 68.22% and Week 24 opacification was 66.11%, then the change would be reported as -2.11%.
次要结局
- Change From Baseline to Week 4 in Each of the 4 Individual Cardinal Chronic Rhinosinusitis (CRS) Symptoms (AM, Instantaneous).(Baseline, Week 4)
- Time to First Acute Exacerbation of Chronic Sinusitis(24 Weeks)
- Change From Baseline to Defined Timepoints - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains(24 Weeks)
- Change From Baseline to Week 8 and 12 in Composite Symptom Score (Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge) for the Total Population and Patients With and Without Previous Sinus Surgery.(8 weeks, 12 weeks.)
- Change From Baseline to Weeks 8 and 12 in Nasal Congestion Measured by Instantaneous Morning (AM) and Evening (PM) Diary Symptom Scores(8 Weeks; 12 Weeks)
- Change From Baseline to Weeks 8 and 12 in Nasal Discharge (Anterior and/or Posterior) Measured by Instantaneous AM and PM Diary Symptom Scores(Baseline, Week 8, Week 12)
- Change From Baseline to Weeks 8 and 12 in Facial Pain or Pressure Sensation Measured by Instantaneous AM and PM Diary Symptom Scores(Baseline, Week 8, Week 12)
- Change From Baseline to Weeks 8 and 12 in Sense of Smell Scores Measured by Instantaneous AM and PM Diary Symptom Scores(Baseline, Week 8, Week 12)
- Change From Baseline to Week 24/ET in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses for Patients With and Without Previous Sinus Surgery(Baseline, Week 24)
- Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score(Baseline, Week 24)
- Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for Each Sinus Pair(Baseline, Week 24)
- Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus, as Measured by CT Scan Assessment.(Baseline, Week 24)
- Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus, as Measured by CT Scan Assessment.(24 weeks)
- Change From Baseline to Week 24/ET in the Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between Maxillary and Ethmoid Sinuses, as Measured by CT Scan Assessment.(24 weeks)
- Change From Baseline to Week24/ET in the Lund-Mackay Staging System Scores for the Ethmoids and Maxillary Sinuses Combined(24 Weeks)
- Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System Total Score(Baseline, Week 24)
- Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Sinus Pairs.(Baseline, Week 24)
- Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined(24 weeks)
- Change From Baseline to Week 24/ET in the Zinreich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations(24 Weeks)
- Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI)(12 Weeks, 24 Weeks)
- Change in Overall Health From Baseline to Week 4 and Week 24/ET as Measured by the Percent of Subjects Improved as Indicated by the Patient Global Impression of Change (PGIC)(Week 4, Week 24)
- Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2)(24 Weeks)
- Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Component Score (MCS).(24 Weeks)
- Change in the SF-36v2 Physical Component Score (PCS)(24 Weeks)
- Change in Depressive Symptoms From Baseline to Week 24/ET as Measured by Change in the Severity of Depression as Measured by the Quick Inventory of Depression Symptomatology (QIDS)(24 Weeks)
- Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS)(24 Weeks)
- Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™(24 Weeks)
- Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument(24 Weeks)
- Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument(24 Weeks)
- Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery at Baseline and Week 24(Baseline, Week 24)
- Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention at Baseline and Week 24.(Baseline, Week 24)
- Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery(Week 24)
研究者
研究点 (87)
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