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

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)

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03157167

Enrollment

Registered

2017-05-17

Start date

2017-12-01

Completion date

2020-03-30

Last updated

2025-03-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV Infections, Kaposi Sarcoma

Keywords

Kaposi Sarcoma, KS, HIV

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.

Interventions

DRUGTc99m-tilmanocept

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

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

DIAGNOSTIC

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. The subject has provided written informed consent with HIPAA authorization before the initiation of any study-related procedures. 2. The subject is at least 18 years of age at the time of consent. 3. The subject is HIV positive. 4. 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

1. The subject is pregnant or lactating. 2. The subject has received chemotherapy or radiation therapy to KS sites within six weeks of enrollment. 3. The subject has known sensitivity to dextran. 4. The subject has received an investigational product within 30 days prior to the Tc 99m tilmanocept administration on Day 1. 5. The subject has received any radiopharmaceutical within 7 days prior to the administration of Tc 99m tilmanocept on Day 1. 6. 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.

Design outcomes

Primary

Measure	Time frame	Description
To Determine the Safety of Escalating Doses of Tc 99m Tilmanocept in HIV Subjects With Biopsy-confirmed KS.	10 days after IV Tc 99m tilmanocept administration	Cohort 1 (100 mcg/ 5mCi) was conducted first. A safety data review meeting was held after completion of Cohort 1 and again after completion of Cohort 2 at which the principal investigators and sponsor representatives reviewed the safety data to determine whether to proceed to the next cohort. All cohorts were evaluated for safety. Safety evaluations included AEs, clinical laboratory tests, vital signs, physical examinations, and ECGs. The data table includes the number of safety signals detected during the evaluation for each cohort.

Secondary

Measure	Time frame	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	10 days after IV Tc 99m tilmanocept administration	Presents Tc 99m tilmanocept KS lesion localization in each cohort. IV injections occurred in all three cohorts. SC injections occurred in cohort 3 only.
Qualify and Quantify Tc 99m Tilmanocept Localization Intensity on Imaging With CD206 Locale and Quantity by Histology and IHC in Biopsied KS Lesions to Determine Optimal IV Dose.	10 days after IV Tc 99m tilmanocept administration	Localization intensity for each biopsied and clinically defined lesion was to be determined by Planar and/or SPECT/CT imaging. The results would have been average pixel intensity and percentage above background. Note: Cohort 1 was completed before this outcome measure was introduced, therefore no cohort 1 subjects were evaluated for this outcome measure.
Localization Concordance of Subcutaneous Injection and IV Injection	10 days after IV Tc 99m tilmanocept administration	Per lesion/region concordance of IV vs subcutaneous Tc 99m localization with anatomical areas of active KS defined by confirmed diagnosis or clinical symptomology. Note: IV routes of administration are used in all three cohorts. Cohort 3 is the only SC route of administration.
Exploratory: Quantify HHV8 in Biopsied KS Lesions. Mean and Standard Deviation Results.	10 days after IV Tc 99m tilmanocept administration	Quantify HHV8 in biopsied KS lesions by using qPCR. Note: Cohort 1 was completed before this outcome measure was introduced, therefore no cohort 1 subjects were evaluated for this outcome measure. If there is identification of HHv8, that would confirm the presence of KS cells in the biopsied tissue.
Exploratory: Quantify HHV8 in Biopsied KS Lesions. Median Results.	10 days after IV Tc 99m tilmanocept administration	Quantify HHV8 in biopsied KS lesions by using qPCR. Note: Cohort 1 was completed before this outcome measure was introduced, therefore no cohort 1 subjects were evaluated for this outcome measure. If there is identification of HHv8, that would confirm the presence of KS cells in the biopsied tissue.

Countries

United States

Participant flow

Pre-assignment details

One subject was enrolled and injected with Tc 99m tilmanocept but after experiencing an AE (anxiety) did not undergo imaging and withdrew from the trial. The safety population is defined as any subject that was injected with Tc 99m tilmanocept (15 subjects). The intent to diagnose population is defined as all subjects that completed the trial (14 subjects), unless otherwise noted in the outcome measure. One subject in cohort 1 withdrew after injection and was not imaged.

Participants by arm

Arm	Count
100 mcg/5 mCi Tc99m-Tilmanocept Four subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 5 mCi. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	5
100 mcg/10 mCi Tc99m-Tilmanocept Four subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 10 mCi. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	4
200 mcg/5 mCi Tc99m-Tilmanocept 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. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	6
Total	15

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Withdrawal by Subject	1	0	0

Baseline characteristics

Characteristic	100 mcg/5 mCi Tc99m-Tilmanocept	100 mcg/10 mCi Tc99m-Tilmanocept	200 mcg/5 mCi Tc99m-Tilmanocept	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	1 Participants	0 Participants	0 Participants	1 Participants
Age, Categorical Between 18 and 65 years	4 Participants	4 Participants	6 Participants	14 Participants
Age, Continuous	58.0 years	53.5 years	38.5 years	54.0 years
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	1 Participants	1 Participants	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants	3 Participants	5 Participants	13 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	0 Participants	1 Participants	2 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	2 Participants	0 Participants	1 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	1 Participants	0 Participants	2 Participants
Race (NIH/OMB) White	1 Participants	3 Participants	3 Participants	7 Participants
Region of Enrollment United States	5 Participants	4 Participants	6 Participants	15 Participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	5 Participants	4 Participants	6 Participants	15 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 5	0 / 4	0 / 6
other Total, other adverse events	1 / 5	1 / 4	0 / 6
serious Total, serious adverse events	0 / 5	0 / 4	0 / 6

Outcome results

Primary

To Determine the Safety of Escalating Doses of Tc 99m Tilmanocept in HIV Subjects With Biopsy-confirmed KS.

Cohort 1 (100 mcg/ 5mCi) was conducted first. A safety data review meeting was held after completion of Cohort 1 and again after completion of Cohort 2 at which the principal investigators and sponsor representatives reviewed the safety data to determine whether to proceed to the next cohort. All cohorts were evaluated for safety. Safety evaluations included AEs, clinical laboratory tests, vital signs, physical examinations, and ECGs. The data table includes the number of safety signals detected during the evaluation for each cohort.