Nonalcoholic SteatohepatitisPhase 1NCT03332940
Safety Evaluation of IV Tc 99m Tilmanocept and Comparison of Imaging With Sulfur Colloid in Subjects With and Without NASH
A Phase 1 study testing Tc 99M Sulfur Colloid and Tc99m-tilmanocept in people with Nonalcoholic Steatohepatitis and NASH - Nonalcoholic Steatohepatitis, run by Navidea Biopharmaceuticals at 1 site in United States.
Trial summary
This is a prospective, open-label, multicenter, safety, comparative study of IV administered Tc99m-tilmanocept and unfiltered Tc99m sulfur colloid in the detection of and assessment of three dimensional tessellation localization to the liver in subjects with and without moderate to severe nonalcoholic steatohepatitis… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Nonalcoholic Steatohepatitis, NASH - Nonalcoholic Steatohepatitis
- What is being tested?
- Tc 99M Sulfur Colloid and Tc99m-tilmanocept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Dec 2017to 10 Mar 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- ALL SUBJECTS:
- The subject has provided written informed consent with HIPAA (Health Information Portability and Accountability Act) authorization before the initiation of any study-related procedures.
- The subject is ≥18 years of age at the time of consent.
- The subject has a body mass index (BMI) between 18 and 45.
- CONTROL SUBJECTS:
- The subject is deemed to be clinically free of any infectious/inflammatory disease(s) for at least 4 weeks prior to the consent date.
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- The subject has not taken any antibiotics for at least 4 weeks prior to the consent date.
- NASH SUBJECTS:
- 4. The subject has biopsy-confirmed NASH within 12 months prior to enrollment. 5. The subject has a NAFLD Activity Score (NAS) of ≥ 4, with a score of at least 1 for each steatosis, lobular inflammation, and hepatocyte ballooning.
- 6. The subject has fibrosis staging of F3-F4.
Who cannot join
- ALL SUBJECTS:
- The subject is pregnant or lactating.
- The subject size or weight is not compatible with imaging per the investigator.
- The subject has received radiation therapy or chemotherapy or has a previous diagnosis of cancer other than basal cell carcinoma.
- The subject has renal insufficiency as demonstrated by a GFR of < 60 mL/min.
- The subject has a chronic or persistent infection or has any condition that would, in the opinion of the examining physician, preclude their participation.
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- The subject has a known allergy to or has had an adverse reaction to dextran exposure.
- The subject has received an investigational product within 30 days prior to the Tc 99m sulfur colloid administration.
- The subject has received any radiopharmaceutical within 7 days prior to the administration of Tc 99m sulfur colloid.
- The subject is HIV positive.
- The subject has a history of alcohol abuse or currently consumes alcohol in excess of 3 drinks/day for men or 2 drinks/day for women.
- The subject has hepatitis B or C.
- CONTROL SUBJECTS:
- The subject has hepatic insufficiency as demonstrated by ALT (alanine aminotransferase [SGPT]) or AST (aspartate aminotransferase [SGOT]) greater than two times the upper limit of normal (ULN).
- The subject has been diagnosed with NASH, NAFLD, or other chronic liver disease.
- The subject has been diagnosed with metabolic syndrome or Type I or II diabetes.
- NASH SUBJECTS:
- 12. The subject has any chronic liver disease aside from NASH/NAFLD.
- 13. The subject has uncontrolled diabetes as indicated by an A1c >9% within the 3 months prior to enrollment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Evaluation of the Safety of Intravenous (IV) Tc 99m Tilmanocept and a Comparison of Localization to Tc 99m Sulfur Colloid in Subjects With Nonalcoholic Steatohepatitis (NASH) and Healthy Controls (HC)
This is a prospective, open-label, multicenter, safety, comparative study of IV administered Tc99m-tilmanocept and unfiltered Tc99m sulfur colloid in the detection of and assessment of three dimensional tessellation localization to the liver in subjects with and without moderate to severe nonalcoholic steatohepatitis (NASH) by planar and SPECT/CT imaging.
This study is designed to evaluate the safety and tolerability of Tc99m-tilmanocept in subjects with NASH.
- Being tested
- Tc 99M Sulfur Colloid, Tc99m-tilmanocept
- Keywords
- Tc99m-tilmanocept, Tilmanocept, NASH, Nonalcoholic Steatohepatitis
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tc 99M Sulfur ColloidDrug
Also called Sulfur colloid
Sulfur colloid is a radiotracer that is indicated for imaging areas of functional reticuloendothelial cells in the liver, spleen, and bone marrow.
Tc99m-tilmanoceptDrug
Also called Tilmanocept, 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 |
|---|---|---|
| NASH subjects | Experimental | All subjects will receive a single IV injection of unfiltered sulfur colloid radiolabeled with 8 mCi Tc99m on study day 0. All subjects will receive a single IV injection of 200 mcg tilmanocept radiolabeled with 8 mCi Tc99m on study day 3. Receives: Drug: Tc 99M Sulfur Colloid; Drug: Tc99m-tilmanocept |
| Healthy controls | Experimental | All subjects will receive a single IV injection of unfiltered sulfur colloid radiolabeled with 8 mCi Tc99m on study day 0. All subjects will receive a single IV injection of 200 mcg tilmanocept radiolabeled with 8 mCi Tc99m on study day 3. Receives: Drug: Tc 99M Sulfur Colloid; Drug: Tc99m-tilmanocept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Drug Reaction
Proportion of subjects experiencing noxious pharmacologic activity/an Adverse Drug Reaction (ADR).
Measured: 5 days after Tc 99m tilmanocept injection
Secondary outcomes (3)
Localization of Tc 99m tilmanocept
Determine the three dimensional tessellation localization of Tc 99m tilmanocept by planar and SPECT/CT imaging in subjects with NASH and asymptomatic controls.
Measured: 5 days after Tc 99m tilmanocept injection
Localization of Tc 99m sulfur colloid
Determine the three dimensional tessellation localization of unfiltered Tc 99m sulfur colloid by planar and SPECT/CT imaging in subjects with NASH and asymptomatic controls.
Measured: 5 days after Tc 99m tilmanocept injection
Localization Distribution Comparison
Comparison of liver localization distribution tessellation pattern intensities between Tc 99m tilmanocept and unfiltered Tc 99m sulfur colloid.
Measured: 5 days after Tc 99m tilmanocept injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start6 Dec 2017
- Primary completion10 Mar 2019
- Study completion10 Mar 2019
Why it stopped: No meaningful differences in the pattern of liver uptake were observed between Tc 99m tilmanocept and the comparator (Tc 99m sulfur colloid) after a review of the first six subjects.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Nonalcoholic SteatohepatitisStudies 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
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Navidea Biopharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Blue, MD, Study director, Navidea Biopharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03332940
- Sponsor's protocol ID
- NAV3-30
- Status last verified
- Jan 2023
- First submitted
- 1 Nov 2017
- Last updated
- 24 Dec 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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 27866590Cope, 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.
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Evaluation of the Safety of Intravenous (IV) Tc 99m Tilmanocept and a Comparison of Localization to Tc 99m Sulfur Colloid in Subjects With Nonalcoholic Steatohepatitis (NASH) and Healthy Controls (HC)
- ClinicalTrials.gov ID
- NCT03332940
- Acronym / sponsor ID
- NAV3-30
- Keywords
- Tc99m-tilmanocept, Tilmanocept, NASH, Nonalcoholic Steatohepatitis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No meaningful differences in the pattern of liver uptake were observed between Tc 99m tilmanocept and the comparator (Tc 99m sulfur colloid) after a review of the first six subjects.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Navidea BiopharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 6 Dec 2017 (actual)
- Primary completion
- 10 Mar 2019 (actual)
- Study completion
- 10 Mar 2019 (actual)
- First posted
- 6 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, open-label, multicenter, safety, comparative study of IV administered Tc99m-tilmanocept and unfiltered Tc99m sulfur colloid in the detection of and assessment of three dimensional tessellation localization to the liver in subjects with and without moderate to severe nonalcoholic steatohepatitis (NASH) by planar and SPECT/CT imaging.
This study is designed to evaluate the safety and tolerability of Tc99m-tilmanocept in subjects with NASH.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NASH subjects | Experimental | Drug: Tc 99M Sulfur Colloid, Drug: Tc99m-tilmanoceptAll subjects will receive a single IV injection of unfiltered sulfur colloid radiolabeled with 8 mCi Tc99m on study day 0. All subjects will receive a single IV injection of 200 mcg tilmanocept radiolabeled with 8 mCi Tc99m on study day 3. |
| Healthy controls | Experimental | Drug: Tc 99M Sulfur Colloid, Drug: Tc99m-tilmanoceptAll subjects will receive a single IV injection of unfiltered sulfur colloid radiolabeled with 8 mCi Tc99m on study day 0. All subjects will receive a single IV injection of 200 mcg tilmanocept radiolabeled with 8 mCi Tc99m on study day 3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- ALL SUBJECTS:
- 4. The subject has biopsy-confirmed NASH within 12 months prior to enrollment. 5. The subject has a NAFLD Activity Score (NAS) of ≥ 4, with a score of at least 1 for each steatosis, lobular inflammation, and hepatocyte ballooning.
- 6. The subject has fibrosis staging of F3-F4.
Key exclusion criteria (19 listed)
- ALL SUBJECTS:
- 12. The subject has any chronic liver disease aside from NASH/NAFLD.
- 13. The subject has uncontrolled diabetes as indicated by an A1c >9% within the 3 months prior to enrollment.
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 |
|---|---|---|
| Tc 99M Sulfur ColloidAlso: Sulfur colloidSulfur colloid is a radiotracer that is indicated for imaging areas of functional reticuloendothelial cells in the liver, spleen, and bone marrow. | Drug | Healthy controls, NASH subjects |
| Tc99m-tilmanoceptAlso: Tilmanocept, LymphoseekTilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. | Drug | Healthy controls, NASH subjects |
Primary outcome
Adverse Drug Reaction
Time frame: 5 days after Tc 99m tilmanocept injection
Proportion of subjects experiencing noxious pharmacologic activity/an Adverse Drug Reaction (ADR).
3 secondary outcomes
Localization of Tc 99m tilmanocept
Time frame: 5 days after Tc 99m tilmanocept injection
Localization of Tc 99m sulfur colloid
Time frame: 5 days after Tc 99m tilmanocept injection
Localization Distribution Comparison
Time frame: 5 days after Tc 99m tilmanocept injection
Results and safety
The study was stopped early (reason given: No meaningful differences in the pattern of liver uptake were observed between Tc 99m tilmanocept and the comparator (Tc 99m sulfur colloid) after a review of the first six subjects.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2024.
- Background: 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.
- 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.
- 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, Inc.
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 Tc 99M Sulfur Colloid and Tc99m-tilmanocept in people with Nonalcoholic Steatohepatitis and NASH - Nonalcoholic Steatohepatitis, 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 10 inclusion and 19 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: stopped early, as of the sponsor's last update on 24 Dec 2024. 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?
The study was stopped early (reason given: No meaningful differences in the pattern of liver uptake were observed between Tc 99m tilmanocept and the comparator (Tc 99m sulfur colloid) after a review of the first six subjects.). Results are not available in the source record.
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?
Adverse Drug Reaction (time frame: 5 days after Tc 99m tilmanocept injection). 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 NCT03332940, 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 24 Dec 2024.