FLUTE is a randomized, double-blind, placebo-controlled dose-ranging study of 4 total dailydoses of APT-1011 versus placebo in 100 adult subjects (at least 18 years of age) diagnosed with EoE. During the single-blind run-in/baseline symptom assessment, the subjects will receive placebo 30 minutes after breakfast and HS (at bedtime). APT-1011 will be administered in 4 doses: Placebo 30 minutes after breakfast and 1.5 mg HS (at bedtime), 1.5 mg BID (30 minutes after breakfast and at bedtime; total daily dose of 3 mg), 3 mg HS (at bedtime), and 3 mg BID (30 minutes after breakfast and at bedtime; total daily dose of 6 mg), compared with matching placebo administered 30 minutes after breakfast and HS (at bedtime). The randomization scheme is discussed in Section 188.8.131.52. Efficacy (histological response), safety, and PK of APT-1011 will be examined.
FLUTE will enroll around 100 adult (at least 18 years of age) subjects (see Section 8.1 for a discussion of the potential number of subjects to participate in each part).
FLUTE is planned to be performed at approximately 60 active sites in North America (US and Canada) and Western Europe (Belgium, Germany and Spain). The study will be conducted in several parts (Screening, 4-week single-blind placebo run-in and Baseline Symptom Assessment, and 2 treatment parts [Part 1 and Part 21) with a Follow-up Visit to occur 2 weeks after the final dose of study drug. Subjects who enter and complete FLUTE will be in the study for up to 62 weeks until the last subject completes Week 28.
- Diagnosis of EoE must be confirmed by symptoms, histology, and historical documentation of failed treatment on 8 weeks of high-dose PPI. For the purposes of FLUTE, high-dose PPI is defined as 20 mg BID omeprazole or 20 to 40 BID mg of any marketed PPI; maintenance doses of PPls are not acceptable. A lack of response to PPI therapy is defined as 15 PEAK eosinophils/HPF with at least 5 biopsies including both proximal and distal specimens after 8 weeks of high dose PPI treatment.
- Documentation of PPI failure prior to initial diagnosis or by documentation of PPI failure at the time of Screening is required. The subjects may be pre-screened but should not be consented, sign an ICF, or be offered participation in FLUTE if they have not met the diagnostic criteria for EoE that requires that they fail an 8-week trial of high dose PPls EXCEPT those that have taken PP ls for 8 weeks will use the EGO within the study for this documentation. The Investigator and potential subject must make the decision to complete a PPI trial independent of any considerations of the study. There is insufficient time to do the 8-week trial within the current study. Should a subject be consented in error and screen fails due to this point, they may be rescreened as described in the protocol.
- Have a subject-reported history of 3 episodes of dysphagia (difficulty with food going down) in the 7 days prior to Screening;
- Have a 7-day Global EoE Symptom Score >3 at baseline. This will be performed on paper during the Screening visit.
- 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;
FLUTE will be conducted in multiple parts: Screening (4 weeks), 4-week Single-Blind Placebo Run-in/Baseline Symptom Assessment, Part 1 (14-week induction),
Part 2 Maintenance (Weeks 14 to up to Week 52) and a Follow-up Visit to be completed 2 weeks after the last dose of study drug. Subjects who complete all parts of FLUTE will be in the study for up to 62 weeks until the last subject completes Week 28.
Procedures: Blood samples: Approximately 138.0 ml (about 28 teaspoons) of blood will be taken during the entire 62 weeks of the study. No more than 13.5 ml (about 3 teaspoons) of blood will be taken at any one visit. A maximum of 12 urine samples will be collected. A maximum of 4 uper GI endoscopies will be performed (2 for phase 1 and 2 for phase 2). Four ACTH stimulation tests will be perform during the duration of the study (2 for phase 1 and 2 for phase2)
Visits: Maximum of 15 visit between phase 1 and 2