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| ID | Type | Description | Link |
|---|---|---|---|
| 1R44CA192859-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Cancer Institute (NCI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 100 mcg/5 mCi Tc99m-Tilmanocept | Experimental | Four subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 5 mCi. |
|
| 100 mcg/10 mCi Tc99m-Tilmanocept | Experimental | Four subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 10 mCi. |
|
| 200 mcg/5 mCi Tc99m-Tilmanocept | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tc99m-tilmanocept | Drug | Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 10 days after IV Tc 99m tilmanocept administration |
| Measure | Description | Time Frame |
|---|---|---|
| Per Subject Localization Rate of Tc 99m Tilmanocept in at Least One KS Suspected or Confirmed Lesion by Planar and/or SPECT/CT Imaging | Presents Tc 99m tilmanocept KS lesion localization in each cohort. IV injections occurred in all three cohorts. SC injections occurred in cohort 3 only. | 10 days after IV Tc 99m tilmanocept administration |
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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:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Blue, MD | Navidea Biopharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zuckerberg San Francisco General Hospital | San Francisco | California | 94143 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | 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. | ||
| 27866590 | Result | 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. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Safety population, including all subjects injected with Tc99m tilmanocept. | Posted | Number | Safety Signals | 10 days after IV Tc 99m tilmanocept administration |
|
50 days
No deaths occurred during the trial. No SAEs were reported. No other significant AEs were reported.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 100 mcg/5 mCi Tc99m-Tilmanocept | Four subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 5 mCi. Note that one additional subject was injected with Tc 99m tilmanocept but withdrew after experiencing anxiety (AE). This brings the safety population for this cohort to 5. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anxiety | Psychiatric disorders | MedDRA v20.1 | Systematic Assessment | Cohort 1 subject who withdrew after injection. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael Blue, MD | Navidea Biopharmaceuticals | 6145714313 | mblue@navidea.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 1, 2019 | Aug 21, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 30, 2020 | Dec 18, 2024 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 10, 2019 | Aug 21, 2024 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D012514 | Sarcoma, Kaposi |
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
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Not provided
| ID | Term |
|---|---|
| C431884 | technetium-diethylenetriaminepentaacetic acid-mannosyl-dextran |
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Not provided
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|
| 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. |
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. |
| 10 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. Note: IV routes of administration are used in all three cohorts. Cohort 3 is the only SC route of administration. | 10 days after IV Tc 99m tilmanocept administration |
| Exploratory: Quantify HHV8 in Biopsied KS Lesions. Mean and Standard Deviation Results. | 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. | 10 days after IV Tc 99m tilmanocept administration |
| Exploratory: Quantify HHV8 in Biopsied KS Lesions. Median Results. | 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. | 10 days after IV Tc 99m tilmanocept administration |
| 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. |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | 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. |
| OG002 | 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. |
|
|
| Secondary | Per Subject Localization Rate of Tc 99m Tilmanocept in at Least One KS Suspected or Confirmed Lesion by Planar and/or SPECT/CT Imaging | Presents Tc 99m tilmanocept KS lesion localization in each cohort. IV injections occurred in all three cohorts. SC injections occurred in cohort 3 only. | The intent to diagnose population, including subjects that were imaged and completed the trial. | Posted | Count of Participants | Participants | 10 days after IV Tc 99m tilmanocept administration |
|
|
|
| Secondary | 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. | 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. | The intent to diagnose population, including subjects that were imaged and completed the trial, excluding cohort 1 as this cohort was completed before this outcome measure was introduced. | Posted | Count of Participants | Participants | 10 days after IV Tc 99m tilmanocept administration |
|
|
|
| Secondary | 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. Note: IV routes of administration are used in all three cohorts. Cohort 3 is the only SC route of administration. | The intent to diagnose population, including subjects that were imaged and completed the trial. | Posted | Count of Units | Lesions | 10 days after IV Tc 99m tilmanocept administration | Lesions | Lesions |
|
|
|
| Secondary | Exploratory: Quantify HHV8 in Biopsied KS Lesions. Mean and Standard Deviation Results. | 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. | The intent to diagnose population, including subjects that were imaged and completed the trial, excluding cohort 1 as this cohort was completed before this outcome measure was introduced. | Posted | Mean | Standard Deviation | HHV8 (RFU) | 10 days after IV Tc 99m tilmanocept administration |
|
|
|
| Secondary | Exploratory: Quantify HHV8 in Biopsied KS Lesions. Median Results. | 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. | The intent to diagnose population, including subjects that were imaged and completed the trial, excluding cohort 1 as this cohort was completed before this outcome measure was introduced. | Posted | Median | Full Range | HHV8 (RFU) | 10 days after IV Tc 99m tilmanocept administration |
|
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 1 |
| 5 |
| EG001 | 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. | 0 | 4 | 0 | 4 | 1 | 4 |
| EG002 | 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. | 0 | 6 | 0 | 6 | 0 | 6 |
|
| Bronchitis | Infections and infestations | MedDRA v20.1 | Systematic Assessment |
|
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| D012509 |
| Sarcoma |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009383 | Neoplasms, Vascular Tissue |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| Localized KS Lesions for SC Injection |
|
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| Biopsy Sample Collection Criteria Met |
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| Participants with Valid Biopsy Imaged by SPECT/CT |
|
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| Participants with Valid Biopsy Imaged by Planar Image |
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| Participant with Valid Biopsy that was able to be Quantified |
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| Localized Lesions via SC |
|
|