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

Primary Purpose

Kaposi Sarcoma, HIV Infections

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Tc99m-tilmanocept

About this trial

This is an interventional diagnostic trial for Kaposi Sarcoma focused on measuring Kaposi Sarcoma, KS, HIV

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:
1. Confirmed cutaneous KS/oral lesions without edema.
2. Confirmed cutaneous KS/oral lesions with edema.
3. 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.

Sites / Locations

Zuckerberg San Francisco General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

100 mcg/5 mCi Tc99m-Tilmanocept

100 mcg/10 mCi Tc99m-Tilmanocept

200 mcg/5 mCi Tc99m-Tilmanocept

Arm Description

Four subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 5 mCi.

Four subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 10 mCi.

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.

Outcomes

Primary Outcome Measures

Adverse Drug Reaction

Proportion of subjects experiencing noxious pharmacologic activity/an Adverse Drug Reaction (ADR).

Secondary Outcome Measures

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.

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.

Localization Intensity

Localization intensity for each biopsied and clinically defined lesion, as determined by quantitative SPECT gamma counts.

Per subject localization

Per subject localization rate of Tc 99m tilmanocept in areas other than KS by planar and/or SPECT/CT imaging.

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.

Biopsy analyses

Per biopsied lesion proportion of CD206-expressing cells and total CD206, as determined by histology and relative IHC fluorescence.

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.

Full Information

NCT ID

NCT03157167

First Posted

May 4, 2017

Last Updated

July 14, 2020

Sponsor

Navidea Biopharmaceuticals

Collaborators

National Institutes of Health (NIH), National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT03157167

Brief Title

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

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

December 1, 2017 (Actual)

Primary Completion Date

November 5, 2019 (Actual)

Study Completion Date

March 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Navidea Biopharmaceuticals

Collaborators

National Institutes of Health (NIH), National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Kaposi Sarcoma, HIV Infections

Keywords

Kaposi Sarcoma, KS, HIV

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

100 mcg/5 mCi Tc99m-Tilmanocept

Arm Type

Experimental

Arm Description

Four subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 5 mCi.

Arm Title

100 mcg/10 mCi Tc99m-Tilmanocept

Arm Type

Experimental

Arm Description

Four subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 10 mCi.

Arm Title

200 mcg/5 mCi Tc99m-Tilmanocept

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Tc99m-tilmanocept

Other Intervention Name(s)

Lymphoseek

Intervention Description

Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.

Primary Outcome Measure Information:

Title

Adverse Drug Reaction

Description

Proportion of subjects experiencing noxious pharmacologic activity/an Adverse Drug Reaction (ADR).

Time Frame

7 days after IV Tc 99m tilmanocept administration

Secondary Outcome Measure Information:

Title

Per Subject Localization

Description

Per subject localization rate of Tc 99m tilmanocept in at least one KS suspected or confirmed lesion by planar and/or SPECT/CT imaging.

Time Frame

7 days after IV Tc 99m tilmanocept administration

Title

Localization concordance with physical observations

Description

Per lesion/region concordance of Tc 99m localization with anatomical areas of active KS defined by confirmed diagnosis or clinical symptomology.

Time Frame

7 days after IV Tc 99m tilmanocept administration

Title

Localization Intensity

Description

Localization intensity for each biopsied and clinically defined lesion, as determined by quantitative SPECT gamma counts.

Time Frame

7 days after IV Tc 99m tilmanocept administration

Title

Per subject localization

Description

Per subject localization rate of Tc 99m tilmanocept in areas other than KS by planar and/or SPECT/CT imaging.

Time Frame

7 days after IV Tc 99m tilmanocept administration

Title

Per area localization rate

Description

Per area localization rate of Tc 99m tilmanocept in the most frequently identified areas other than KS by planar and/or SPECT CT imaging.

Time Frame

7 days after IV Tc 99m tilmanocept administration

Title

Biopsy analyses

Description

Per biopsied lesion proportion of CD206-expressing cells and total CD206, as determined by histology and relative IHC fluorescence.

Time Frame

7 days after IV Tc 99m tilmanocept administration

Title

Localization concordance of subcutaneous injection and IV injection

Description

Per lesion/region concordance of IV vs subcutaneous Tc 99m localization with anatomical areas of active KS defined by confirmed diagnosis or clinical symptomology.

Time Frame

7 days after IV Tc 99m tilmanocept administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Blue, MD

Organizational Affiliation

Navidea Biopharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Zuckerberg San Francisco General Hospital

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

Citation

Cope, F.O., W. Metz, et al. Innovations in receptor-targeted precision imaging at Navidea: diagnosis up close and personal. Nature Outlook (31 October 2013); S125-S129.

Results Reference

background

PubMed Identifier

27866590

Citation

Cope FO, Abbruzzese B, Sanders J, Metz W, Sturms K, Ralph D, Blue M, Zhang J, Bracci P, Bshara W, Behr S, Maurer T, Williams K, Walker J, Beverly A, Blay B, Damughatla A, Larsen M, Mountain C, Neylon E, Parcel K, Raghuraman K, Ricks K, Rose L, Sivakumar A, Streck N, Wang B, Wasco C, Williams A, Schlesinger LS, Azad A, Rajaram MVS, Jarjour W, Young N, Rosol T, McGrath M. Corrigendum to the inextricable axis of targeted diagnostic imaging and therapy: An immunological natural history approach [Nucl Med Biol 43 (2016) 215-225]. Nucl Med Biol. 2016 Dec;43(12):837. doi: 10.1016/j.nucmedbio.2016.10.001. No abstract available.

Results Reference

result

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

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