An Evaluation of Tc 99m Tilmanocept by Intravenous (IV) and Subcutaneous (SC) Injection in Kaposi Sarcoma (KS)

Study Overview
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Brief Summary
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To determine the safety of escalating IV doses of Tc 99m tilmanocept in HIV (human immunodeficiency virus) subjects with confirmed KS and to compare results obtained from subcutaneous and IV administrations of Tc 99m tilmanocept in the same subjects.

Detailed Description
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This is a Manocept Platform prospective, single-center, open-label, non-randomized, dose escalation, comparative, safety study of intravenously and subcutaneously injected Tc 99m tilmanocept in the localization and detection of cutaneous and non-cutaneous KS tumor(s) in subjects with biopsy-confirmed KS. Three IV doses (µg/mCi) of tilmanocept will be evaluated in three cohort groups. One subcutaneous dose will be evaluated in cohort group 3. This study is designed to evaluate the safety and tolerability of escalating doses of IV Tc 99m tilmanocept and to compare results obtained from IV and subcutaneous administrations of Tc 99m tilmanocept in the same subjects. Whole body planar as well as SPECT/CT imaging will be performed to provide greater resolution of areas of Tc 99m tilmanocept localization. A biopsy of a non-visceral KS lesion will be taken to correlate pathology with Tc 99m tilmanocept localization. This study is designed to evaluate the use of Tc 99m tilmanocept as an imaging agent in HIV-positive subjects with known KS by evaluating localization in known and unknown cutaneous and non-cutaneous lesions.

Official Title
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An Evaluation of the Safety of Escalating Doses of Tc 99m Tilmanocept by Intravenous (IV) Injection and a Comparison to Subcutaneous (SC) Injection in Human Immunodeficiency Virus (HIV) Subjects Diagnosed With Kaposi Sarcoma (KS)

Conditions
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Kaposi Sarcoma, HIV Infections

Intervention / Treatment
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* Drug: Tc99m-tilmanocept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has provided written informed consent with HIPAA authorization before the initiation of any study-related procedures. The subject is at least 18 years of age at the time of consent. The subject is HIV positive. The subject has a biopsy-confirmed diagnosis of KS and is classified into one of the categories below: Confirmed cutaneous KS/oral lesions without edema. Confirmed cutaneous KS/oral lesions with edema. Confirmed cutaneous KS/oral lesions with or without edema and suspected non-cutaneous KS due to clinical symptomology or confirmed non-cutaneous KS lesion(s). Exclusion Criteria: The subject is pregnant or lactating. The subject has received chemotherapy or radiation therapy to KS sites within six weeks of enrollment. The subject has known sensitivity to dextran. The subject has received an investigational product within 30 days prior to the Tc 99m tilmanocept administration on Day 1. The subject has received any radiopharmaceutical within 7 days prior to the administration of Tc 99m tilmanocept on Day 1. Any condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100 mcg/5 mCi Tc99m-Tilmanocept<br>Four subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 5 mCi. | 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;|
| Experimental: 100 mcg/10 mCi Tc99m-Tilmanocept<br>Four subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 10 mCi. | 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;|
| Experimental: 200 mcg/5 mCi Tc99m-Tilmanocept<br>Up to six subjects will receive a single subcutaneous injection and a single IV injection of 200 micrograms of Tc99m tilmanocept radiolabeled with 5 mCi. | 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). | 7 days after IV Tc 99m tilmanocept administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Per Subject Localization | Per subject localization rate of Tc 99m tilmanocept in at least one KS suspected or confirmed lesion by planar and/or SPECT/CT imaging. | 7 days after IV Tc 99m tilmanocept administration | 
| Localization concordance with physical observations | Per lesion/region concordance of Tc 99m localization with anatomical areas of active KS defined by confirmed diagnosis or clinical symptomology. | 7 days after IV Tc 99m tilmanocept administration | 
| Localization Intensity | Localization intensity for each biopsied and clinically defined lesion, as determined by quantitative SPECT gamma counts. | 7 days after IV Tc 99m tilmanocept administration | 
| Per subject localization | Per subject localization rate of Tc 99m tilmanocept in areas other than KS by planar and/or SPECT/CT imaging. | 7 days after IV Tc 99m tilmanocept administration | 
| Per area localization rate | Per area localization rate of Tc 99m tilmanocept in the most frequently identified areas other than KS by planar and/or SPECT CT imaging. | 7 days after IV Tc 99m tilmanocept administration | 
| Biopsy analyses | Per biopsied lesion proportion of CD206-expressing cells and total CD206, as determined by histology and relative IHC fluorescence. | 7 days after IV Tc 99m tilmanocept administration | 
| Localization concordance of subcutaneous injection and IV injection | Per lesion/region concordance of IV vs subcutaneous Tc 99m localization with anatomical areas of active KS defined by confirmed diagnosis or clinical symptomology. | 7 days after IV Tc 99m tilmanocept administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kaposi Sarcoma, KS, HIV