Evaluation of the Precision and Sensitivity of Tilmanocept Uptake Value (TUV) on Tc 99m Tilmanocept Planar Imaging
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Tc 99m tilmanocept
Intervention description: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a prospective, open-label, multicenter, single and repeated-dose study designed to evaluate the reliability and sensitivity of TUV assessments in healthy controls and subjects with active RA.
Masking: None (Open Label)
Enrollment: 116.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: RA; healthy control; tilmanocept; diagnostic; imaging

Summary:

      This clinical trial will look at scans of the hands and wrists taken from healthy control
      subjects (HCs) and from subjects with rheumatoid arthritis (RA). Before each scan, subjects
      will be given an injection of Tc 99m tilmanocept to help the scan identify inflammation in
      the hand and wrist joints, which can be a part of the RA disease. Data from the scans will be
      used to calculate a number referred to as tilmanocept uptake value (or TUV) that is a measure
      of how much Tc 99m tilmanocept has located in the joints. The questions this trial aims to
      answer are:

        -  How consistent are the scan results (TUVs) when the scans are repeated over time?

        -  What are normal TUVs in healthy people? This will help define abnormally high values in
           people with RA.

        -  Are TUVs calculated early after a person starts a new drug to treat RA able to predict
           whether that person will have a good response to the drug later on (after it has had
           time to take full effect several weeks later)?
    

Eligibility criteria:

        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. ARMS 1 and 2 (only): The subject has agreed to not engage in any diet, lifestyle, or
             medication changes until study completion.

             HEALTHY CONTROL SUBJECTS

          3. The subject is between 18 and 80 years of age at the time of consent.

          4. The subject is deemed to be clinically free of any inflammatory disease(s) 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 NSAIDs) and has not
             taken 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 first imaging visit (Day 0).

        7. If the subject is receiving 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 or oral corticosteroids, the dose has been stable for
        > 28 days prior to first imaging visit (Day 1). The corticosteroid dose must be ≤ 10 mg/day
        of prednisone or an equivalent steroid dose.

        9. ARM 3 (only): The subject is receiving anti-rheumatic treatment and is a candidate for
        initiation of, or change to, a new anti-TNFα bDMARD treatment.

        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.

          9. The subject has received intra-articular corticosteroid injections ≤ 8 weeks prior to
             the first imaging visit (Day 0).

         10. The subject has received any radiopharmaceutical within 7 days or 10 half-lives prior
             to the administration of Tc 99m tilmanocept.