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)?
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
116
Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
Imaging Endpoints
Scottsdale, Arizona, United States
Axis Clinical Trials
Los Angeles, California, United States
University of California San Francisco
San Francisco, California, United States
Innovation Medical Research Center
Palmetto Bay, Florida, United States
Physician Research Collaboration
Lincoln, Nebraska, United States
University Hospitals
Cleveland, Ohio, United States
Kettering Medical Center
Kettering, Ohio, United States
Central States Research
Tulsa, Oklahoma, United States
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Arms 1 & 2: Assess Camera-specific Precision of TUV
The camera-specific precision of TUVjoint in subjects with active RA and Healthy Controls (HCs), which is described as the Root Mean Square Difference (RMSD) between the 15-minute planar images (referred to as A and B images at 60 and 180 minutes). The RMSD is calculated as the square root of the mean squared deviation from zero.
Time frame: Day 0 tilmanocept injection followed by imaging at 60 minutes (60A) and 75 minutes (60B) and at 180 minutes (180A) and 195 minutes (180B).
Arms 1 and 2: Stability of the Mean/Variance Relationship
The stability of the mean/variance relationship, which is assessed by comparing the Coefficient of Variation (CV) of TUVjoint and TUVglobal in subjects with active RA and in healthy control subjects at 60 and 180 minutes.
Time frame: Day 0 tilmanocept injection followed by imaging at 60 minutes and 180 minutes.
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy
The Kendall rank correlation of the change in global TUV from baseline to 5 weeks (ΔTUVglobal\[5w\]) and response to new anti-TNFα bDMARD therapy defined by the change from baseline of CDAI to 12 ± 1 weeks and 24 ± 1 weeks (ΔCDAI12w and ΔCDAI24w).• The Kendall rank correlation of ΔTUVglobal\[5w\] and response to new anti-TNFα bDMARD therapy from baseline to 12 ± 1 weeks and 24 ± 1 weeks defined by ACR Response Criteria (ΔACR12w and ΔACR24w)
Time frame: Imaging (60 minutes after tilmanocept injection) on Day 0 and at 5 weeks after new therapy initiation; Assessment of CDAI and ACR Response Criteria at 12 and 24 weeks after new therapy initiation.
Longitudinal (8-day) Variation of TUV
Longitudinal (8-day) variation of TUV analyzed for each DAS28 joint, defined as the root mean square deviation (RMSD) and 95% confidence interval for the RMSD for each joint at Day 0 vs Day 8
Time frame: Imaging (60 minutes after tilmanocept injection) on Day 0 and Day 8
Arm 1 Normal Ranges of TUVjoint
The normal range of tilmanocept uptake values (TUVs) in hand and wrist joints of healthy control subjects, expressed as the mean and standard deviation. TUV is defined as the average pixel intensity of the region of interest (hand or wrist joint) divided by the average pixel intensity of the reference region (includes the region from one wrist region of interest diameter above the wrist region of interest down to the fingertips)
Time frame: Images obtained 60 minutes after tilmanocept injection on Day 0.
Qualitative Evaluations of SPECT/CT as an Indication of Bone Involvement Rather Than Localization Within the Synovial Space in the Hands and Wrists of Arm 2 Subjects
Percent of Arm 2 subjects who had SPECT/CT scans who were determined to have bone involvement rather than localization within the synovial space of the hands and wrists
Time frame: A SPECT/CT scan was performed at approximately 210 minutes after the tilmanocept injection on Day 8 of the trial.
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy)
The correlation of the TUVglobal\[baseline\] and response to new anti-TNFα bDMARD therapy defined by the change from baseline (CFB) of CDAI to 12 ± 1 weeks and 24 ± 1 weeks (ΔCDAI12w and ΔCDAI24w, respectively) and by ACR Response Criteria (ACR12w and ACR24w, respectively).
Time frame: Images were obtained 60 minutes after tilmanocept injection on Day 0. New anti-TNFα therapy was initiated after completion of Day 0 procedures. CDAI and ACR were assessed on Day 0 and again 12 and 24 weeks after initiation of new anti-TNFα therapy.
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