An Evaluation of the Safety of Intravenous Tc 99m Tilmanocept and a Comparison of Imaging With Sulfur Colloid in Subjects With and Without NASH

Study Overview
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Brief Summary
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This is a prospective, open-label, multicenter, safety, comparative study of IV administered Tc99m-tilmanocept and unfiltered Tc99m sulfur colloid in the detection of and assessment of three dimensional tessellation localization to the liver in subjects with and without moderate to severe nonalcoholic steatohepatitis (NASH) by planar and SPECT/CT imaging. This study is designed to evaluate the safety and tolerability of Tc99m-tilmanocept in subjects with NASH.

Official Title
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An Evaluation of the Safety of Intravenous (IV) Tc 99m Tilmanocept and a Comparison of Localization to Tc 99m Sulfur Colloid in Subjects With Nonalcoholic Steatohepatitis (NASH) and Healthy Controls (HC)

Conditions
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Nonalcoholic Steatohepatitis, NASH - Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: Tc 99M Sulfur Colloid
* Drug: Tc99m-tilmanocept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ALL SUBJECTS: The subject has provided written informed consent with HIPAA (Health Information Portability and Accountability Act) authorization before the initiation of any study-related procedures. The subject is ≥18 years of age at the time of consent. The subject has a body mass index (BMI) between 18 and 45. CONTROL SUBJECTS: The subject is deemed to be clinically free of any infectious/inflammatory disease(s) for at least 4 weeks prior to the consent date. The subject has not taken any antibiotics for at least 4 weeks prior to the consent date. NASH SUBJECTS: 4. The subject has biopsy-confirmed NASH within 12 months prior to enrollment. 5. The subject has a NAFLD Activity Score (NAS) of ≥ 4, with a score of at least 1 for each steatosis, lobular inflammation, and hepatocyte ballooning. 6. The subject has fibrosis staging of F3-F4. Exclusion Criteria: ALL SUBJECTS: The subject is pregnant or lactating. The subject size or weight is not compatible with imaging per the investigator. The subject has received radiation therapy or chemotherapy or has a previous diagnosis of cancer other than basal cell carcinoma. The subject has renal insufficiency as demonstrated by a GFR of < 60 mL/min. The subject has a chronic or persistent infection or has any condition that would, in the opinion of the examining physician, preclude their participation. The subject has a known allergy to or has had an adverse reaction to dextran exposure. The subject has received an investigational product within 30 days prior to the Tc 99m sulfur colloid administration. The subject has received any radiopharmaceutical within 7 days prior to the administration of Tc 99m sulfur colloid. The subject is HIV positive. The subject has a history of alcohol abuse or currently consumes alcohol in excess of 3 drinks/day for men or 2 drinks/day for women. The subject has hepatitis B or C. CONTROL SUBJECTS: The subject has hepatic insufficiency as demonstrated by ALT (alanine aminotransferase [SGPT]) or AST (aspartate aminotransferase [SGOT]) greater than two times the upper limit of normal (ULN). The subject has been diagnosed with NASH, NAFLD, or other chronic liver disease. The subject has been diagnosed with metabolic syndrome or Type I or II diabetes. NASH SUBJECTS: 12. The subject has any chronic liver disease aside from NASH/NAFLD. 13. The subject has uncontrolled diabetes as indicated by an A1c >9% within the 3 months prior to enrollment.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tc99m-sulfur colloid + Tc99m-tilmanocept<br>All subjects will receive a single IV injection of unfiltered sulfur colloid radiolabeled with 8 mCi Tc99m on study day 0. All subjects will receive a single IV injection of 200 mcg tilmanocept radiolabeled with 8 mCi Tc99m on study day 3. | Drug: Tc 99M Sulfur Colloid<br>* Sulfur colloid is a radiotracer that is indicated for imaging areas of functional reticuloendothelial cells in the liver, spleen, and bone marrow.<br>* Other names: Sulfur colloid;Drug: Tc99m-tilmanocept<br>* Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.<br>* Other names: Lymphoseek;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Drug Reaction | Proportion of subjects experiencing noxious pharmacologic activity/an Adverse Drug Reaction (ADR). | 5 days after Tc 99m tilmanocept injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Localization of Tc 99m tilmanocept | Determine the three dimensional tessellation localization of Tc 99m tilmanocept by planar and SPECT/CT imaging in subjects with NASH and asymptomatic controls. | 5 days after Tc 99m tilmanocept injection | 
| Localization of Tc 99m sulfur colloid | Determine the three dimensional tessellation localization of unfiltered Tc 99m sulfur colloid by planar and SPECT/CT imaging in subjects with NASH and asymptomatic controls. | 5 days after Tc 99m tilmanocept injection | 
| Localization Distribution Comparison | Comparison of liver localization distribution tessellation pattern intensities between Tc 99m tilmanocept and unfiltered Tc 99m sulfur colloid. | 5 days after Tc 99m tilmanocept injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tilmanocept, NASH, Nonalcoholic Steatohepatitis, Tc99m-tilmanocept