Evaluation of the Precision and Sensitivity of Tilmanocept Uptake Value (TUV) on Tc 99m Tilmanocept Planar Imaging

This trial is a prospective, open-label, multicenter, single and repeated-dose study designed to evaluate the reliability and sensitivity of TUV assessments in healthy control subjects and subjects with active RA.

This study is stratified into 3 arms. The first 2 arms, consisting of [1] disease-free HCs and [2] clinically diagnosed RA subjects on stable treatment, respectively, are designed to evaluate the image re-image and/or test re-test (i.e., repeated dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals.

The third arm consists of clinically-diagnosed subjects with active RA who are candidates for initiation of, or change to, a new anti-TNFα bDMARD therapy. This arm is designed to assess the efficacy of TUVglobal as an early predictor of response to the new anti-TNFα bDMARD therapy.

Inclusion criteria

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.
• 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

• The subject is between 18 and 80 years of age at the time of consent.
• 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.
• 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.
• 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:

• The subject is at least 18 years of age and was ≥ 18 years of age at the time of RA diagnosis.

• 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).

• 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]).

• 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 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 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.

• 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

• 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.
• The subject has received intra-articular corticosteroid injections ≤ 8 weeks prior to the first imaging visit (Day 0).
• The subject has received any radiopharmaceutical within 7 days or 10 half-lives prior to the administration of Tc 99m tilmanocept.