Kaposi SarcomaPhase 1NCT03157167
An Evaluation of Tc 99m Tilmanocept by Intravenous (IV) and Subcutaneous (SC) Injection in Kaposi Sarcoma (KS)
A Phase 1 study testing Tc99m-tilmanocept in people with Kaposi Sarcoma and HIV Infections, run by Navidea Biopharmaceuticals at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kaposi Sarcoma, HIV Infections
- What is being tested?
- Tc99m-tilmanocept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2017to 30 Mar 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Zuckerberg San Francisco General Hospital
San Francisco, California, 94143
About this study
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)
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.
Read the 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.
- Conditions
- Kaposi Sarcoma, HIV Infections
- Being tested
- Tc99m-tilmanocept
- Keywords
- Kaposi Sarcoma, KS, HIV
- Medical subject headings
- Sarcoma, Kaposi, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tc99m-tilmanoceptDrug
Also called Lymphoseek
Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Tc99m-tilmanocept |
| 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. Receives: Drug: Tc99m-tilmanocept |
| 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. Receives: Drug: Tc99m-tilmanocept |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 10 days after IV Tc 99m tilmanocept administration
Secondary outcomes (5)
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.
Measured: 10 days after IV Tc 99m tilmanocept administration
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 10 days after IV Tc 99m tilmanocept administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2017
- Study start1 Dec 2017
- Primary completion5 Nov 2019
- Study completion30 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Kaposi SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Navidea Biopharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Michael Blue, MD, Study director, Navidea Biopharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03157167
- Sponsor's protocol ID
- NAV3-24
- Other IDs
- 1R44CA192859-01
- Status last verified
- Jul 2020
- First submitted
- 4 May 2017
- Last updated
- 5 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
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.
PubMed 27866590
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03157167
- Acronym / sponsor ID
- NAV3-24
- Conditions
- Kaposi Sarcoma, HIV Infections
- Keywords
- Kaposi Sarcoma, KS, HIV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Navidea BiopharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Study start
- 1 Dec 2017 (actual)
- Primary completion
- 5 Nov 2019 (actual)
- Study completion
- 30 Mar 2020 (actual)
- First posted
- 17 May 2017 (actual)
- Results
- Posted 5 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 100 mcg/5 mCi Tc99m-Tilmanocept | Experimental | Drug: Tc99m-tilmanoceptFour subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 5 mCi. |
| 100 mcg/10 mCi Tc99m-Tilmanocept | Experimental | Drug: Tc99m-tilmanoceptFour subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 10 mCi. |
| 200 mcg/5 mCi Tc99m-Tilmanocept | Experimental | Drug: Tc99m-tilmanoceptUp to six subjects will receive a single subcutaneous injection and a single IV injection of 200 micrograms of Tc99m tilmanocept radiolabeled with 5 mCi. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tc99m-tilmanoceptAlso: LymphoseekTilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. | Drug | 100 mcg/10 mCi Tc99m-Tilmanocept, 100 mcg/5 mCi Tc99m-Tilmanocept, 200 mcg/5 mCi Tc99m-Tilmanocept |
Primary outcome
To Determine the Safety of Escalating Doses of Tc 99m Tilmanocept in HIV Subjects With Biopsy-confirmed KS.
Time frame: 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.
5 secondary outcomes
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: 10 days after IV Tc 99m tilmanocept administration
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.
Time frame: 10 days after IV Tc 99m tilmanocept administration
Localization Concordance of Subcutaneous Injection and IV Injection
Time frame: 10 days after IV Tc 99m tilmanocept administration
Exploratory: Quantify HHV8 in Biopsied KS Lesions. Mean and Standard Deviation Results.
Time frame: 10 days after IV Tc 99m tilmanocept administration
Exploratory: Quantify HHV8 in Biopsied KS Lesions. Median Results.
Time frame: 10 days after IV Tc 99m tilmanocept administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundCope, 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 publication: PubMed 27866590Cope 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Blue, MD study director
Navidea Biopharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tc99m-tilmanocept in people with Kaposi Sarcoma and HIV Infections, run by Navidea Biopharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To Determine the Safety of Escalating Doses of Tc 99m Tilmanocept in HIV Subjects With Biopsy-confirmed KS. (time frame: 10 days after IV Tc 99m tilmanocept administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03157167, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2025.