Safety Evaluation of IV Tc 99m Tilmanocept and Comparison of Imaging With Sulfur Colloid in Subjects With and Without NASH

NCT03332940 | Terminated Phase 1 FDA Drug

• 1 other identifier: NAV3-30
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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 (NASH) by planar and SPECT/CT imaging. This study is designed to evaluate the safety and tolerability of Tc99m-tilmanocept in subjects with NASH.

Conditions

Nonalcoholic Steatohepatitis; NASH - Nonalcoholic Steatohepatitis

Keywords

Tc99m-tilmanocept; Tilmanocept; NASH; Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Adverse Drug Reaction

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

  5 days after Tc 99m tilmanocept injection

Secondary Outcomes (3)

• Localization of Tc 99m tilmanocept

  5 days after Tc 99m tilmanocept injection

• Localization of Tc 99m sulfur colloid

  5 days after Tc 99m tilmanocept injection

• Localization Distribution Comparison

  5 days after Tc 99m tilmanocept injection

Other Outcomes (2)

• Tc 99m tilmanocept Localization Distribution of SPECT/CT vs Elastography

  5 days after Tc 99m tilmanocept injection

• Tc 99m sulfur colloid Localization Distribution of SPECT/CT vs Elastography

  5 days after Tc 99m tilmanocept injection

Study Arms (2)

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.

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.

Drug: Tc 99M Sulfur Colloid; Drug: Tc99m-tilmanocept

Interventions

Tc 99M Sulfur Colloid DRUG

Sulfur colloid is a radiotracer that is indicated for imaging areas of functional reticuloendothelial cells in the liver, spleen, and bone marrow.

Also known as: Sulfur colloid

Healthy controls; NASH subjects

Tc99m-tilmanocept DRUG

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

Also known as: Tilmanocept, Lymphoseek

Healthy controls; NASH subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• The subject has not taken any antibiotics for at least 4 weeks prior to the consent date.
• NASH SUBJECTS:
• \. 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.
• \. The subject has fibrosis staging of F3-F4.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Navidea Biopharmaceuticals: lead

Study Sites (1)

Kettering Medical Center

Kettering, Ohio, 45429, United States

Location

Related Publications (2)

• 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.

  PMID: 27866590 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.

  BACKGROUND

Related Links

• Navidea Biopharmaceuticals, Inc.

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Technetium Tc 99m Sulfur Colloid; technetium-diethylenetriaminepentaacetic acid-mannosyl-dextran

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Sulfur Compounds; Inorganic Chemicals; Technetium Compounds

Study Officials

• Michael Blue, MD

  Navidea Biopharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2017
• First Posted: November 6, 2017
• Study Start: December 6, 2017
• Primary Completion: March 10, 2019
• Study Completion: March 10, 2019
• Last Updated: December 24, 2024

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)