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

Primary Purpose

Eosinophilic Esophagitis

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
NDX-3315
Sponsored by
NexEos Diagnostics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Eosinophilic Esophagitis focused on measuring Eosinophilic Esophagitis, EoE, Diagnostic

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • University of PennsylvaniaRecruiting
  • University of UtahRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Regimen 5

Regimen 10

Regimen 1

Regimen 10 (Supine)

Arm Description

NDX-3315 delivered via oral syringe at ~ 3 mL per minute .

NDX-3315 delivered via oral syringe at ~ 1.5 mL per minute.

NDX-3315 delivered via oral syringe single ~15 mL dose.

NDX-3315 delivered via oral syringe at ~ 1.5 mL per minute while in supine position.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Radioactivity of blood collected from participants exposed to NDX-3315.
Blood samples will be collected to measure radioactivity as counts per minute(cpm).
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.
Counts of SPECT imaging
SPECT images will be analyzed for radioactive counts per region of interest(ROI) of the esophagus.
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.
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.
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.
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.

Full Information

First Posted
February 10, 2023
Last Updated
May 4, 2023
Sponsor
NexEos Diagnostics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05757856
Brief Title
A Study to Investigate Safety and Tolerability of NDX-3315 in Healthy Participants and Patients With Eosinophilic Esophagitis
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 20, 2023 (Actual)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
August 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NexEos Diagnostics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Eosinophilic Esophagitis
Keywords
Eosinophilic Esophagitis, EoE, Diagnostic

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Open-label multi-arm study.
Masking
Outcomes Assessor
Masking Description
The pathologist and immunostaining analyst receiving study participant biopsies for analysis, as well as the radiologist scoring the scans will be blinded to regimen assignment, EoE diagnosis and other test results.
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Regimen 5
Arm Type
Experimental
Arm Description
NDX-3315 delivered via oral syringe at ~ 3 mL per minute .
Arm Title
Regimen 10
Arm Type
Experimental
Arm Description
NDX-3315 delivered via oral syringe at ~ 1.5 mL per minute.
Arm Title
Regimen 1
Arm Type
Experimental
Arm Description
NDX-3315 delivered via oral syringe single ~15 mL dose.
Arm Title
Regimen 10 (Supine)
Arm Type
Experimental
Arm Description
NDX-3315 delivered via oral syringe at ~ 1.5 mL per minute while in supine position.
Intervention Type
Drug
Intervention Name(s)
NDX-3315
Intervention Description
Oral solution
Primary Outcome Measure Information:
Title
The proportion of all participants with AEs following administration of NDX-3315
Description
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.
Time Frame
From start of study drug administration up to End of study (EOS) ( Up to 3 Weeks)
Secondary Outcome Measure Information:
Title
Partial thromboplastin time (PTT) as marker of pharmacodynamic (PD)
Description
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.
Time Frame
Baseline, 2 hours post-dose (Up to 1 Week)
Title
Radioactivity of blood collected from participants exposed to NDX-3315.
Description
Blood samples will be collected to measure radioactivity as counts per minute(cpm).
Time Frame
2.5 hours post-dose (Up to 1 Week)
Title
Visual ratings of SPECT images
Description
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.
Time Frame
Up to 45 minutes after dose
Title
Counts of SPECT imaging
Description
SPECT images will be analyzed for radioactive counts per region of interest(ROI) of the esophagus.
Time Frame
Up to 45 minutes after dose
Title
Peak eosinophil counts per high power field(HPF)
Description
A blinded pathologist will perform peak eosinophil counts per high powered field(HPF) on biopsy specimens of the esophagus.
Time Frame
Up to 10 days after last dose
Title
Deposition of eMBP1
Description
A blinded immunostaining analyst will perform analysis of deposition of eMBP1 (Eosinophil major basic protein 1) via immunostaining of biopsy specimens of the esophagus.
Time Frame
Up to 10 days after last dose
Title
EoE Endoscopic Reference Score (EREFS)
Description
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.
Time Frame
Up to 10 days after last dose
Title
EoE Symptom Collection Questionnaire
Description
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.
Time Frame
Baseline (All participants), Day 1 (EoE participants only)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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, 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
NDX-3315-1001 Study Team
Phone
(484) 267-3909
Email
clinicaltrials.gov@nexeosdx.com
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Manager
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Research Manager

12. IPD Sharing Statement

Plan to Share IPD
No

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

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