Comparison of Tc 99m Tilmanocept Imaging With IHC Analysis of CD206 Expression in Synovial Tissue of Subjects With RA

NCT04078191 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: NAV3-322018-003418-41
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 4

Brief Summary

This study is a comparison of quantitative Tc 99m tilmanocept imaging with IHC analysis of CD206 expression in synovial tissue of RA subjects.

Conditions

Rheumatoid Arthritis

Keywords

tilmanocept; RA imaging; synovial biopsy

Outcome Measures

Primary Outcomes (1)

• Correlation Between Joint-specific Tilmanocept Uptake and CD206 Expression

  The correlation between joint-specific tilmanocept uptake value (TUVjoint) and the number and area fraction of CD206 expression as determined by IHC assessment.

  Through study completion, up to 45 days

Secondary Outcomes (2)

• Correlation Between Joint-specific Tilmanocept Uptake and CD68 and CD163 Expression

  Through study completion, up to 45 days

• Classification of Synovial Anatomic Pathotype by IHC Assessment

  Through study completion, up to 45 days

Other Outcomes (3)

• Exploratory Objective: Correlation Between CD206, CD68, and CD163 Expression

  Through study completion, up to 45 days

• Safety Evaluation - AEs

  Through study completion, up to 45 days

• Safety Evaluation - Laboratory Tests, ECGs, and Vital Signs

  Through study completion, up to 45 days

Study Arms (1)

RA Subjects on Stable Therapy

EXPERIMENTAL

RA subjects who are on stable treatment will receive a single dose of 150 mcg tilmanocept radiolabeled with 10 mCi Tc 99m.

Drug: Tc 99m tilmanocept

Interventions

Tc 99m 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: Lymphoseek

RA Subjects on Stable Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject has provided written informed consent with HIPAA (Health Information Portability and Accountability Act) or equivalent authorization before the initiation of any study-related procedures.
• Women and men of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) for the duration of the study.
• The subject is at least 18 years of age and was ≥ 18 years of age at the time of RA diagnosis.
• The subject has RA as determined by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria (score of ≥ 6/10 at or before screening).
• The subject has a 28-joint disease activity score (DAS28) of ≥ 3.2 (includes the C-reactive protein \[CRP\] test and visual analog scale \[VAS\]).
• Subjects receiving traditional DMARDs must have been on therapy for ≥ 90 days and at a stable dose for ≥ 30 days prior to the first imaging visit (Day 0).
• If the subject is receiving biologic disease-modifying antirheumatic drug (bDMARD) or janus kinase (JAK) inhibitor therapy, they have been at a stable dose \> 180 days prior to the first imaging visit (Day 0).
• If the subject is receiving NSAIDs (nonsteroidal anti-inflammatory drug) or oral corticosteroids, the dose has been at a stable dose for ≥ 28 days prior to imaging. The corticosteroid dose should be ≤ 10 mg/day of prednisone or an equivalent steroid dose.
• The subject has a hand or wrist joint with a minimum ultrasound gray-scale synovitis score of 2 (range 0 to 3).

You may not qualify if:

• The subject is pregnant or lactating.
• The subject size or weight is not compatible with imaging per the investigator.
• The subject has had or is currently receiving radiation therapy or chemotherapy.
• The subject has renal insufficiency as demonstrated by a glomerular filtration rate of \< 60 mL/min.
• The subject has hepatic insufficiency as demonstrated by ALT (alanine aminotransferase \[SGPT\]) or AST (aspartate aminotransferase \[SGOT\]) greater than 3 times the upper limit of normal.
• The subject has any severe, acute, or chronic medical conditions and/or psychiatric conditions and/or laboratory abnormalities that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration that would deem the subject inappropriate for study 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 tilmanocept administration (Day 0).
• The subject has received intra-articular corticosteroids ≤ 8 weeks prior to imaging (Day 0).
• The subject has received any radiopharmaceutical within 7 days or 10 half-lives prior to the administration of Tc 99m tilmanocept (Day 0).
• The subject has an intolerance to anesthetic and antiseptic agents indicated for the synovial biopsy procedure.
• The subject is currently receiving anticoagulants (oral anti-platelet agents are permitted) or has a condition that is contraindicated with ultrasound-guided synovial biopsy e.g., needle phobia.

Sponsors & Collaborators

• Navidea Biopharmaceuticals: lead

Study Sites (4)

Attune Health

Beverly Hills, California, 90210, United States

Location

Northwestern University

Chicago, Illinois, 60208, United States

Location

Barts Hospital

London, England, United Kingdom

Location

Royal Free Hospital

London, England, United Kingdom

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

technetium-diethylenetriaminepentaacetic acid-mannosyl-dextran

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

Analysis of NAV3-32 trial data was halted prior to evaluation of the acquired images. Preliminary analysis of data from other trials indicated that the ability of Tc 99m tilmanocept imaging to predict response to anti-TNFα therapy in RA patients would not be sufficient for the product to be commercially viable. Therefore, further development of the product for this indication was halted.

Results Point of Contact

• Title: Michael Blue, MD
• Organization: Navidea

mblue@navidea.com

6145714313

Study Officials

• Michael Blue, MD

  Navidea Biopharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2019
• First Posted: September 4, 2019
• Study Start: September 14, 2021
• Primary Completion: July 9, 2024
• Study Completion: July 9, 2024
• Last Updated: January 8, 2025
• Results First Posted: January 8, 2025

Record last verified: 2024-07

Locations

GB (2); US (2)