A Study to Investigate Safety and Tolerability of NDX-3315 in Healthy Participants and Patients With Eosinophilic Esophagitis

Study Overview
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Brief Summary
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An open-label phase 1b study to assess the safety and exploratory diagnostic performance of the oral radiopharmaceutical agent NDX-3315 in healthy participants and patients with eosinophilic esophagitis (EoE).

Detailed Description
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This study is a multi-site, Phase 1b, open-label study of orally administered NDX-3315 and esophageal imaging in healthy participants and participants with EoE. Study details include: The study duration or period will be up to around 10 weeks. Participants will receive either one or two doses of NDX-3315 depending on their assigned regimen arm. EoE participants will receive two doses; healthy participants will receive one dose. The visit frequency will be three site visits for healthy participants and four site visits for EoE participants followed by one follow-up phone call visit within the study period.

Official Title
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An Open-label Phase 1b Study Assessing the Safety, Tolerability and Preliminary Diagnostic Performance of a Radioactive Imaging Agent, NDX-3315, in Healthy Adult Participants and Patients With Eosinophilic Esophagitis

Conditions
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Eosinophilic Esophagitis

Intervention / Treatment
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* Drug: NDX-3315


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Participants: • Participants who are healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and electrocardiogram (ECG) assessment. EoE Participants: Documented diagnosis of EoE (based on prior endoscopy with biopsies showing eosinophils ≥15 / HPF); AND History (by patient report) of recurrent dysphagia and/or other related EoE symptoms (with intake of solids off anti-inflammatory therapy) prior to screening; dysphagia is defined as trouble swallowing solid food, or having solid food stuck, by patient report. Exclusion Criteria: Medical Conditions: Participant with presence of any other disease of the GI tract, including cancer, autoimmune esophageal disease, GERD, Barrett's esophagus, eosinophilic gastritis, enteritis, colitis, or proctitis; inflammatory bowel disease; or celiac disease. Known motility disorder of esophagus; achalasia or suspicion thereof. Sleep apnea, if considered by the investigator a concern for the endoscopic procedure. History of recurrent aspiration pneumonia. History of bleeding disorders, liver cirrhosis or esophageal varices. A current malignancy or previous history of cancer in remission for less than 5 years prior to Screening (participants will not be excluded if they had localized carcinoma of the skin that was resected for cure). Participant with a Body Mass Index >40 m2/kg or inability to undergo a CT (or SPECT scan) due to weight limitations. Participant is pregnant or nursing. Prior/Concomitant Therapy: Participant who is on anticoagulation therapy that, in the investigator or Medical Monitor's opinion, cannot safely come off medication. Use of chronic aspirin, nonsteroidal agents, or anti-coagulants within 2 weeks prior to screening. Use of systemic corticosteroids within 3 months or swallowed topical corticosteroids within 6 weeks prior to Screening visit. Participant is being treated with systemic immunosuppression, carafate (sucralfate), or investigational agent of any kind within less than 3 months or 5 half-lives, whichever is longer, prior to Screening visit (this also includes investigational formulations of marketed products). Diagnostic Assessments: Evidence of clinically significant abnormality in the hematological and biochemical assessments at Screening Visit, specifically: International Normalized Ratio (INR) >1.4; platelet count <80,000/μL and creatinine level >2 mg/dL. ECG: QTcF ≥450 msec for males and QTcF ≥470 msec for females at the time of screening. Other Exclusion Criteria: Any condition that would not permit adequate biopsies of the esophagus (e.g., esophageal varices, significant stricture precluding passage of a 9 mm endoscope). Healthy Participants Only: A history or current diagnosis of allergic diseases (e.g., allergic rhinitis/sinusitis, asthma, atopic dermatitis, food allergies) or serum immunoglobulin E (IgE) level ≥100 kU/L.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open-label multi-arm study.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen 5<br>NDX-3315 delivered via oral syringe at   3 mL per minute . | Drug: NDX-3315<br>* Oral solution<br>|
| Experimental: Regimen 10<br>NDX-3315 delivered via oral syringe at   1.5 mL per minute. | Drug: NDX-3315<br>* Oral solution<br>|
| Experimental: Regimen 1<br>NDX-3315 delivered via oral syringe single  15 mL dose. | Drug: NDX-3315<br>* Oral solution<br>|
| Experimental: Regimen 10 (Supine)<br>NDX-3315 delivered via oral syringe at   1.5 mL per minute while in supine position. | Drug: NDX-3315<br>* Oral solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of all participants with AEs following administration of NDX-3315 | An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product and that does not necessarily have causal relationship with this treatment. | From start of study drug administration up to End of study (EOS) ( Up to 3 Weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial thromboplastin time (PTT) as marker of pharmacodynamic (PD) | Blood samples will be collected to measure Partial Thromboplastin Time (PTT), which is a blood test that looks at how long it takes for blood to clot. | Baseline, 2 hours post-dose (Up to 1 Week) | 
| Radioactivity of blood collected from participants exposed to NDX-3315. | Blood samples will be collected to measure radioactivity as counts per minute(cpm). | 2.5 hours post-dose (Up to 1 Week) | 
| Visual ratings of SPECT images | A blinded central reviewer will review SPECT images for uptake of NDX-3315 per region of interest(ROI) of the esophagus using a 5 point scale (0= no uptake to 4 = uptake similar to bowel), with 4 being the worst result. | Up to 45 minutes after dose | 
| Counts of SPECT imaging | SPECT images will be analyzed for radioactive counts per region of interest(ROI) of the esophagus. | Up to 45 minutes after dose | 
| Peak eosinophil counts per high power field(HPF) | A blinded pathologist will perform peak eosinophil counts per high powered field(HPF) on biopsy specimens of the esophagus. | Up to 10 days after last dose | 
| Deposition of eMBP1 | A blinded immunostaining analyst will perform analysis of deposition of eMBP1 (Eosinophil major basic protein 1) via immunostaining of biopsy specimens of the esophagus. | Up to 10 days after last dose | 
| EoE Endoscopic Reference Score (EREFS) | EoE-EREFS are used to measure the endoscopically identified EoE esophageal mucosal characteristics. The stricture (if applicable); exudates (absent, mild, severe); furrows (absent, present); edema (absent, present); crepe paper esophagus (absent, present); overall general appearance incorporating all endoscopically identified EoE findings (i.e., fixed rings, strictures, whitish exudates, furrowing, edema, and crepe paper mucosa). The EoE -EREF score being used in this study has a range from 0-11, with 11 being worst result. | Up to 10 days after last dose | 
| EoE Symptom Collection Questionnaire | A questionnaire will be used to collect study participant symptoms such as severity of EoE dysphasia as well as concerns about pain. Answers will have corresponding score ranging from 1-18, with 18 being the worst result. | Baseline (All participants), Day 1 (EoE participants only) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EoE, Eosinophilic Esophagitis, Diagnostic