Clinical trial NCT05757856: A Study to Investigate Safety and Tolerability of NDX-3315 and NDX-3324 in Healthy Participants and Patients with Eosinophilic Esophagitis
Official title: An Open-label Phase 2 Study Assessing the Safety, Tolerability and Preliminary Diagnostic Performance of a Radioactive Imaging Agent, NDX-3315 and NDX-3324, in Healthy Adult Participants and Patients with Eosinophilic Esophagitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Eosinophilic Esophagitis
Keywords: Eosinophilic Esophagitis
EoE
Diagnostic
Lead sponsor: NexEos Diagnostics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-03-07
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label single-arm study.
Primary purpose: DIAGNOSTIC

Brief summary: An open-label phase 2 study to assess the safety and exploratory diagnostic performance of the oral radiopharmaceutical agent NDX-3315 and NDX-3324 in healthy participants and patients with eosinophilic esophagitis (EoE).

Detailed description: This study is a multi-site, Phase 2, open-label study of orally administered NDX-3315 or NDX-3324 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 or NDX-3324 depending on their assigned regimen arm. EoE participants will receive two doses; healthy participants will receive one dose. There will be a SPECT/CT scan performed at each 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.

Eligibility criteria: 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 which is symptomatic or uncontrolled, 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 (with the exception of low-dose aspirin as long as the dose remains stable and not increased while on study), 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, known allergy to sedative used for endoscopy).
  * Healthy Participants Only: A history or current diagnosis of allergic diseases (Should be discussed with Medical Monitor and PI to decide whether exclusionary), autoimmune disease, chronic rhinosinusitis or serum immunoglobulin E (IgE) level ≥100 kU/L. On any medications including NSAIDS and any over the counter (OTC) medications unless it is birth control or acne medications with the exception of Accutane, or if deemed acceptable to use by Medical Monitor and PI.

Primary outcomes:
measure: The proportion of all participants with AEs following administration of NDX-3315 and NDX-3324
timeFrame: From start of study drug administration up to End of Study (EOS) ( Up to 3 Weeks)
measure: Peak eosinophil counts per high-power field (HPF)
timeFrame: Up to 10 days after last dose
measure: Absolute quantification of SPECT imaging
timeFrame: Up to 45 minutes after dose
measure: Determine Concordance of Outcomes
timeFrame: Up to 10 Days After Last Dose
Secondary outcomes:
measure: Partial Thromboplastin Time (PTT) as marker of pharmacodynamics (PD)
timeFrame: Baseline, 2 hours post-dose (Up to 1 Week)
measure: Radioactivity of blood collected from participants exposed to NDX-3315 and NDX-3324.
timeFrame: 2.5 hours post-dose (Up to 1 Week)
measure: Visual ratings of SPECT images
timeFrame: Up to 45 minutes after dose
measure: Deposition of eMBP1
timeFrame: Up to 10 days after last dose
measure: EoE Endoscopic Reference Score (EREFS)
timeFrame: Up to 10 days after last dose
measure: EoE Symptom Collection Questionnaire
timeFrame: Baseline (All participants), Day 1 (EoE participants only)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Univerisity
state: Illinois
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
References: