Development of a Normative Database for Rheumatoid Arthritis (RA) Imaging With Tc99m Tilmanocept

This study will establish a normative database of Tilmanocept Uptake Values (TUVjoint) in healthy controls age-matched to the RA population.

Study Overview

• Status: Active, not recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Tc99m tilmanocept

Detailed Description

This is a prospective, open-label, multicenter, single-dose study designed to develop a normative database of TUVjoint in HCs and to assess the feasibility of qualitative and quantitative SPECT/CT assessments in HCs and subjects with active RA.

This study is stratified into 2 arms. Arm 1 is comprised of HCs and Arm 2 is comprised of HCs and clinically diagnosed RA subjects on stable treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 135
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • San Marcus Research Clinic
    • Palmetto Bay, Florida, United States, 33157
      • Innovation Medical Research Center
  • Ohio
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74137
      • Essential Medical Research
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • Texas
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
    • Webster, Texas, United States, 77598
      • Tranquility Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

ALL SUBJECTS

1. The subject has provided written informed consent with HIPAA (Health Information Portability and Accountability Act) authorization before the initiation of any study-related procedures.

2. The subject has agreed to not engage in any diet, lifestyle, or medication changes until study completion.

   HEALTHY CONTROL SUBJECTS

3. The subject is 30 years of age or greater at the time of consent.
4. The subject is deemed to be clinically free of any inflammatory disease(s), autoimmune disease(s), or arthropathies and has not experienced joint pain for at least 28 days prior to the consent date.
5. The subject is not currently on anti-inflammatory drugs (including non-steroidal anti-inflammatory drugs [NSAIDs]) and has not taken any anti-inflammatories for at least 28 days prior to the consent date.
6. For all ongoing concomitant medications, the subject has maintained a stable dose for at least 28 days prior to the consent date.

CLINICALLY DIAGNOSED ACTIVE RA SUBJECTS

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 moderate to severe RA as determined by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria (score of ≥ 6/10).

5. The subject has a 28-joint disease activity score (DAS28) of ≥ 3.2 (includes the Erythrocyte Sedimentation Rate [ESR] 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 imaging visit (Day 0). 7. If the subject is receiving bDMARD or janus kinase (JAK) inhibitor therapy, they have been at a stable dose > 60 days prior to the imaging visit (Day 0). 8. If the subject is receiving NSAIDs or oral corticosteroids, the dose has been stable for ≥ 28 days prior to the imaging visit (Day 0). The corticosteroid dose must be ≤ 10 mg/day of prednisone or an equivalent steroid dose.

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 is currently receiving radiation therapy or chemotherapy or has received radiation therapy or chemotherapy in the past six months.
4. The subject has had a finger, hand, and/or wrist amputation or hand or wrist joint arthroplasty.
5. The subject has renal insufficiency as demonstrated by a glomerular filtration rate of < 60 mL/min.
6. The subject has hepatic insufficiency as demonstrated by ALT (alanine aminotransferase [SGPT]) or AST (aspartate aminotransferase [SGOT]) greater than 2 times the upper limit of normal.
7. 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 or compromise the safety of the subject or the quality of the data.
8. The subject has any unstable medical illnesses, including hepatic, renal, gastroenterologic, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
9. The subject has a known allergy to or has had an adverse reaction to dextran exposure.
10. The subject has received an investigational product within 30 days prior to Tc 99m tilmanocept administration (Day 0).
11. The subject has received intra-articular corticosteroid injections ≤ 8 weeks prior to Tc 99m tilmanocept administration (Day 0).
12. The subject has received any radiopharmaceutical within 7 days or 10 half-lives prior to Tc 99m tilmanocept administration (Day 0).
13. Healthy Controls only: The subject has a positive rheumatoid factor and an elevated ESR or CRP.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subjects Free of Inflammatory Disease; The first arm will be comprised of HCs who are deemed to be clinically free of inflammatory diseases, arthropathies, and/or arthroplasties and clinically free of joint pain for at least 28 days prior to the consent date.	Drug: Tc99m tilmanocept; Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.; Other Names: Lymphoseek
Experimental: Healthy Controls and RA Subjects on Stable Therapy; The second arm is comprised of [1] disease-free HCs and [2] clinically diagnosed RA subjects on stable treatment.	Drug: Tc99m 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
Normal Limits of TUVjoint in Healthy Subjects	The normal limits of TUVjoint (on a per joint basis) in HC subjects, which are defined as the 5 and 95 percentiles of TUVjoint of bilateral joints (i.e., bilateral wrists, metacarpophalangeal joint [MCPs], proximal interphalangeal [PIPs]).	Up to 39 days
Qualitative Evaluation of SPECT/CT for Tilmanocept Localization	Presence/absence of tilmanocept localization in the hands and wrists will be summarized with frequency counts and percentages by reader and joint.	Up to 39 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normal Distribution of TUVjoint	Applicability of the Normal (Gaussian) distribution to TUVjoint data as assessed by normal quantile plots provided per joint and reader and p-value for the Shapiro-Wilk test of Normality.	Up to 39 days
Quantitative Evaluation of SPECT/CT	Determination of joint-specific standardized uptake value (SUV) from SPECT/CT imaging within synovial spaces of the bilateral hands and wrists in HCs and RA subjects.	Up to 39 days
Planar and SPECT/CT Comparison	Assessment of the predictive value of planar scans for SPECT/CT scans.	Up to 39 days

Collaborators and Investigators

• Sponsor: Navidea Biopharmaceuticals
• Investigators: Study Director: Michael Blue, MD, Navidea Biopharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2021
• Primary Completion (Actual): January 21, 2022
• Study Completion (Anticipated): April 1, 2022

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: June 23, 2021
• First Posted (Actual): July 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 22, 2022
• Last Update Submitted That Met QC Criteria: March 21, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Tilmanocept; RA; Healthy control; HC
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: NAV3-35

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No