FLUTicasone in Eosinophilic Esophagitis (FLUTE): A Randomized, Double-blind, Placebo-controlled, Dose-ranging, and Maintenance Study of APT-1011 in Subjects With Eosinophilic Esophagitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 106
- 试验地点
- 72
- 主要终点
- Percentage of Subjects With ≤6 Peak Eosinophils/High-power Field (HPF)
研究概览
简要总结
Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus, characterized by eosinophilic infiltration and gastrointestinal symptoms. Swallowed, topically acting corticosteroids, such as fluticasone, appear to be effective in resolving acute clinical and pathological features of EoE.
APT-1011 is an orally disintegrating tablet (ODT) formulation of fluticasone propionate. This study is designed to compare the efficacy and safety of APT-1011 with placebo in adults with EoE for an initial 12-week treatment period, followed by an additional 40-week maintenance treatment phase. Histologic response, pharmacokinetics, and dysphagia will be assessed.
详细描述
FLUTE is a phase 2b randomized, double-blind, placebo-controlled dose-ranging clinical trial of APT-1011 versus placebo in 100 adult subjects (≥18 years of age) diagnosed with EoE. Efficacy (including histologic, endoscopic, and symptomatic response), safety, and PK of APT-1011 will be examined. Participants will be given an electronic diary to record symptoms and medication intake daily.
FLUTE will be conducted in several parts (Screening [4 weeks], followed by a 4-week Baseline Symptom Assessment, and 2 treatment parts [Part 1: 14-week Induction and Part 2: 38-week Maintenance]), with a follow-up visit to occur 2 weeks after the final dose of study drug.
In Part 1 of the study, approximately 100 subjects will be randomized 1:1:1:1:1 to receive placebo or one of 4 active doses of APT-1011. All subjects will receive one tablet 30 minutes after breakfast and one tablet at bedtime (HS). The dosing groups include: 1.5 mg HS APT-1011, 1.5 mg twice daily (BID) (total daily dose of 3 mg) APT-1011, 3 mg HS APT-1011, and 3 mg BID (total daily dose of 6 mg) APT-1011, and placebo BID.
In Part 2, all subjects classified as histologic responders at Week 12 will continue to be treated according to the dosing group to which they were randomized, and non-responders will receive single-blind 3 mg BID. All subjects who are histologic non-responders at Week 26 will stop treatment at Week 28 and enter the 2-week follow-up and exit the study. Histologic responders at Week 26 will continue on the same dose until end-of-study at Week 52.
Subjects will complete a follow-up visit 2 weeks after the final dose of study drug. All subjects must have a final EGD within 3 weeks prior to completing the Follow-up Visit unless the subject withdraws consent or has a contraindication to EGD.
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)
盲法说明
Double Blind
入排标准
- 年龄范围
- 18 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 between ≥18 and ≤75 years of age at the time of informed consent
- •Signed informed consent
- •Evidence of EoE defined by ≥15 peak eosinophils per HPF as measured from proximal and distal biopsies
- •Subject-reported history of ≥3 episodes of dysphagia in the 7 days prior to Screening
- •7-day Global EoE Symptom Score >3 at baseline and at screening
- •Willing and able to adhere to study-related treatment regimens, procedures, and visit schedule
排除标准
- •Have known contraindication, hypersensitivity, or intolerance to corticosteroids;
- •Have any physical, mental, or social condition or history of illness or laboratory abnormality that in the Investigator's judgment might interfere with study procedures or the ability of the subject to adhere to and complete the study;
- •Presence of oral or esophageal mucosal infection of any type;
- •Have any mouth or dental condition that prevents normal eating;
- •Have any condition affecting the esophageal mucosa or altering esophageal motility other than EoE;
- •Use of systemic corticosteroids within 60 days prior to Screening, use of inhaled/swallowed corticosteroids within 30 days prior to Screening, or extended use of high-potency dermal topical corticosteroids within 30 days prior to Screening;
- •Initiation of an elimination diet or elemental diet within 30 days before Screening (diet must remain stable after signing ICF);
- •Morning serum cortisol level ≤5 μg/dL (138 nmol/L);
- •Use of biologic immunomodulators in the 24 weeks prior to Screening;
- •Use of calcineurin inhibitors or purine analogues, or potent cytochrome P450 (CYP) 3A4 inhibitors in the 12 weeks prior to Screening;
- •Have a contraindication to or factors that substantially increase the risk of EGD or esophageal biopsy or have narrowing of the esophagus that precludes EGD with a standard 9 mm endoscope;
- •Have a history of an esophageal stricture requiring dilatation within the previous 12 weeks prior to Screening;
- •Have initiated, discontinued or changed dosage regimen of PPIs, H2 antagonists, antacids or antihistamines for any condition such as GERD or allergic rhinitis within 4 weeks prior to qualifying endoscopy. These drugs must remain constant throughout the study.
- •A serum cortisol level <18 μg/dL (497 nmol/L) at 60 minutes with adrenocorticotropic hormone (ACTH) stimulation test using 250 μg cosyntropin (i.e., a positive result on the ACTH stimulation test).
研究组 & 干预措施
APT-1011 3 mg HS
Placebo after breakfast, APT-1011 3 mg HS
干预措施: APT-1011 (Drug)
APT-1011 1.5 mg HS
Placebo after breakfast, APT-1011 1.5 mg HS
干预措施: APT-1011 (Drug)
APT-1011 1.5 mg HS
Placebo after breakfast, APT-1011 1.5 mg HS
干预措施: Placebo (Drug)
APT-1011 1.5 mg BID
APT-1011 1.5 mg after breakfast, APT-1011 1.5 mg HS
干预措施: APT-1011 (Drug)
APT-1011 3 mg HS
Placebo after breakfast, APT-1011 3 mg HS
干预措施: Placebo (Drug)
APT-1011 3 mg BID
APT-1011 3 mg after breakfast, APT-1011 3 mg HS
干预措施: APT-1011 (Drug)
Placebo BID
Placebo 30 minutes after breakfast and HS
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Subjects With ≤6 Peak Eosinophils/High-power Field (HPF)
时间窗: Week 12
Histology (eosinophils per high power field \[HPF\]): percentage of subjects with ≤6 PEAK eosinophils/HPF after assessing at least 5-6 biopsies from the proximal and distal esophagus (\~3 each) where the HPF area is 235 square microns (40 magnification lens with a 22 mm ocular).
次要结局
- Change From Baseline Patient Global Impression of Severity (PGIS) for EoE Symptoms as Assessed Prior to Randomization Post-Baseline Visit(Weeks 4, 8, 12, 14, 18, 22, 26, 28, 36, 44, and 52)
- Change From Baseline PGIS for Difficulty With Food or Pills Going Down as Assessed Prior to Randomization Post-Baseline Visit(Weeks 4, 8, 12, 14, 18, 22, 26, 28, 36, 44, and 52)
- Percentage of Subjects Who Met the Primary Endpoint at Week 12 and Maintained the Primary Endpoint at Weeks 26 and 52(Week 26, and Week 52)
- Percentage of Subjects With a Peak Eosinophils/HPF Number <1 and <15(Week 12, Week 26, and Week 52)
- Change From Baseline Eosinophilic Esophagitis Endoscopic Reference Score (EREFs) at Week 12, 26, and 52(Week 12, Week 26, and Week 52)
- Change From Baseline Global EoE Symptom Score(Week 4, 8, 12, 14, 18, 22, 26, 28, 36, 44, and 52)
- Change in the Number of Dysphagia Episodes(Week 12, Week 26 and Week 52)
- Change From Baseline 7-Day Eosinophilic Esophagitis Activity Index (EEsAI) Total Score(Weeks 12, 26 and 52)
- Change From Baseline 7-Day Eosinophilic Esophagitis Activity Index (EEsAI) Subscores(Weeks 12, 26 and 52)
- Percentage of Subjects With Mean 7-day EEsAI Total Score <20(Weeks 12, 26, and 52)
- Change From Baseline Patient Global Impression of Change (PGIC) for EoE Symptoms as Assessed Prior to Randomization Post-Baseline Visit(Weeks 4, 8, 12, 14, 18, 22, 26, 36, 44, and 52)
- Change From Baseline PGIC of Difficulty With Food or Pills as Assessed Prior to Randomization Post-Baseline Visit(Weeks 4, 8, 12, 14, 18, 22, 26, 36, 44, and 52)
- Percentage of Histologic Non-responders by Dose at Weeks 12, 26, and 52(Weeks 12, 26 and 52)
- Percentage of Subjects Requiring Emergency Endoscopic Food Dis-impaction(before Week 14, between Week 14 and Week 28, between Week 28 and Week 52)
- Percentage of Subjects Requiring Esophageal Dilation(baseline to Week 52)