Comparison of Tc 99m Tilmanocept Quantitative Imaging With Immunohistochemical (IHC) Analysis of CD206 Expression in Synovial Tissue of Subjects With Rheumatoid Arthritis (RA)

April 24, 2023 updated by: Navidea Biopharmaceuticals

A Comparison of Tc 99m Tilmanocept Quantitative Imaging With Immunohistochemical (IHC) Analysis of CD206 Expression in Synovial Tissue From Subjects Clinically Diagnosed With Rheumatoid Arthritis (RA)

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Manocept Platform phase 2b, open-label, multi-center, multinational, non-randomized, single-dose study designed to assess the relationship between quantitative Tc 99m tilmanocept planar imaging and synovial histopathology in subjects clinically diagnosed with RA.

Study Type

Interventional

Enrollment (Anticipated)

24

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United Kingdom
      • London, United Kingdom, EC1M 6BQ
        • Recruiting
        • Barts Health
        • Contact:
        • Principal Investigator:
          • Costantino Pitzalis, MD, PhD, FRCP
      • London, United Kingdom, NW3 2QG
        • Recruiting
        • Royal Free Hospital
        • Contact:
        • Principal Investigator:
          • Richard Stratton, MD
  • United States
    • California
      • Los Angeles, California, United States, 90211
        • Recruiting
        • Attune Health
        • Contact:
          • Natalie Fortune
          • Phone Number: 310-652-0010
        • Principal Investigator:
          • R. Swamy Venuturupalli, MD
    • Illinois
      • Chicago, Illinois, United States, 60611

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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.
  2. 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.
  3. The subject is at least 18 years of age and was ≥ 18 years of age at the time of RA diagnosis.
  4. 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).
  5. 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]).
  6. 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).
  7. 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).
  8. 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.
  9. The subject has a hand or wrist joint with a minimum ultrasound gray-scale synovitis score of 2 (range 0 to 3).

Exclusion Criteria:

  1. The subject is pregnant or lactating.
  2. The subject size or weight is not compatible with imaging per the investigator.
  3. The subject has had or is currently receiving radiation therapy or chemotherapy.
  4. The subject has renal insufficiency as demonstrated by a glomerular filtration rate of < 60 mL/min.
  5. 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.
  6. 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.
  7. The subject has a known allergy to or has had an adverse reaction to dextran exposure.
  8. The subject has received an investigational product within 30 days prior to the Tc 99m tilmanocept administration (Day 0).
  9. The subject has received intra-articular corticosteroids ≤ 8 weeks prior to imaging (Day 0).
  10. The subject has received any radiopharmaceutical within 7 days or 10 half-lives prior to the administration of Tc 99m tilmanocept (Day 0).
  11. The subject has an intolerance to anesthetic and antiseptic agents indicated for the synovial biopsy procedure.
  12. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RA Subjects on Stable Therapy
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
Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
Other Names:
  • Lymphoseek

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between joint-specific tilmanocept uptake and CD206 expression
Time Frame: Through study completion, up to 45 days
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between joint-specific tilmanocept uptake and CD68 and CD163 expression
Time Frame: Through study completion, up to 45 days
The correlation between TUVjoint and the number and area fraction of CD68 and CD163 determined by IHC assessments.
Through study completion, up to 45 days
Classification of synovial anatomic pathotype by IHC assessment
Time Frame: Through study completion, up to 45 days

Classification of synovial anatomic pathology into

  • Lympho-myeloid
  • Diffuse myeloid
  • Pauci-immune fibroid types as a function of CD68, CD163, CD206, CD3, CD20, CD55, and TE7 expression determined by IHC assessments using a polytomous logistic regression model.
Through study completion, up to 45 days
Correlation between CD206, CD68, and CD163 expression
Time Frame: Through study completion, up to 45 days
The correlation between the expression of CD68, CD163, and CD206.
Through study completion, up to 45 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Navidea Biopharmaceuticals

Investigators

  • Study Director: Michael Blue, MD, Navidea Biopharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 14, 2021

Primary Completion (Anticipated)

June 1, 2023

Study Completion (Anticipated)

September 1, 2023

Study Registration Dates

First Submitted

August 21, 2019

First Submitted That Met QC Criteria

September 3, 2019

First Posted (Actual)

September 4, 2019

Study Record Updates

Last Update Posted (Actual)

April 26, 2023

Last Update Submitted That Met QC Criteria

April 24, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NAV3-32
  • 2018-003418-41 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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