Trial Outcomes & Findings for Evaluation of the Precision and Sensitivity of Tilmanocept Uptake Value (TUV) on Tc 99m Tilmanocept Planar Imaging (NCT NCT03938636)

Last Updated: 2023-08-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

116 participants

Primary outcome timeframe

Day 0 tilmanocept injection followed by imaging at 60 minutes (60A) and 75 minutes (60B) and at 180 minutes (180A) and 195 minutes (180B).

Results posted on

2023-08-24

Participant Flow

Participant milestones

Participant milestones
Measure	Subjects Free of Inflammatory Disease Arm 1 comprises disease-free HCs. Arm 1 was designed to evaluate image/re-image consistency (repeatability and stability) of joint-specific and global TUVs across a variety of image acquisition intervals and to collect normative HC data. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	RA Subjects on Stable Therapy Arm 2 comprises clinically diagnosed RA subjects on stable treatment. Arm 2 was designed to evaluate image/re-image and test re-test (i.e., repeat dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	Candidates for Initiation of a New Anti-TNFα Therapy Arm 3 comprises clinically diagnosed RA subjects on stable treatment who are candidates for initiation of, or change to, new anti-TNFα therapy. Arm 3 was designed to assess the efficacy of global TUVs, obtained before and after initiation of a new anti-TNFα therapy, to predict future clinical responsiveness to the new therapy. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
Overall Study STARTED	44	41	31
Overall Study COMPLETED	44	38	28
Overall Study NOT COMPLETED	0	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	RA Subjects on Stable Therapy Arm 2 comprises clinically diagnosed RA subjects on stable treatment. Arm 2 was designed to evaluate image/re-image and test re-test (i.e., repeat dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	Candidates for Initiation of a New Anti-TNFα Therapy Arm 3 comprises clinically diagnosed RA subjects on stable treatment who are candidates for initiation of, or change to, new anti-TNFα therapy. Arm 3 was designed to assess the efficacy of global TUVs, obtained before and after initiation of a new anti-TNFα therapy, to predict future clinical responsiveness to the new therapy. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
Overall Study Protocol Violation	1	1
Overall Study Subject withdrew due to death in family	1	0
Overall Study Missed visit	1	0
Overall Study Adverse Event	0	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Subjects Free of Inflammatory Disease n=44 Participants Arm 1 comprised disease-free HCs. Arm 1 evaluated image/re-image consistency (repeatability and stability) of joint-specific and global TUVs across a variety of image acquisition intervals and collect normative HC data. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	RA Subjects on Stable Therapy n=41 Participants Arm 2 comprised clinically diagnosed RA subjects on stable treatment. Arm 2 evaluated image/re-image and test re-test (i.e., repeat dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	RA Subjects Who Are Candidates for Initiation of a New Anti-TNFα Therapy n=31 Participants Arm 3 comprised clinically diagnosed RA subjects on stable treatment who were candidates for new anti-TNFα therapy. Arm 3 assessed the efficacy of global TUVs, obtained before and after initiation of a new anti-TNFα therapy, to predict future clinical responsiveness to the new therapy. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	Total n=116 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants
Age, Categorical Between 18 and 65 years	44 Participants n=39 Participants	31 Participants n=41 Participants	22 Participants n=35 Participants	97 Participants n=31 Participants
Age, Categorical >=65 years	0 Participants n=39 Participants	10 Participants n=41 Participants	9 Participants n=35 Participants	19 Participants n=31 Participants
Age, Continuous	36.8 years STANDARD_DEVIATION 10.98 • n=39 Participants	56.8 years STANDARD_DEVIATION 11.19 • n=41 Participants	57.0 years STANDARD_DEVIATION 13.68 • n=35 Participants	49.3 years STANDARD_DEVIATION 15.28 • n=31 Participants
Sex: Female, Male Female	26 Participants n=39 Participants	34 Participants n=41 Participants	25 Participants n=35 Participants	85 Participants n=31 Participants
Sex: Female, Male Male	18 Participants n=39 Participants	7 Participants n=41 Participants	6 Participants n=35 Participants	31 Participants n=31 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=39 Participants	3 Participants n=41 Participants	15 Participants n=35 Participants	31 Participants n=31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=39 Participants	38 Participants n=41 Participants	16 Participants n=35 Participants	85 Participants n=31 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=39 Participants	1 Participants n=41 Participants	0 Participants n=35 Participants	1 Participants n=31 Participants
Race (NIH/OMB) Asian	2 Participants n=39 Participants	2 Participants n=41 Participants	1 Participants n=35 Participants	5 Participants n=31 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Black or African American	17 Participants n=39 Participants	11 Participants n=41 Participants	2 Participants n=35 Participants	30 Participants n=31 Participants
Race (NIH/OMB) White	24 Participants n=39 Participants	23 Participants n=41 Participants	28 Participants n=35 Participants	75 Participants n=31 Participants
Race (NIH/OMB) More than one race	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=39 Participants	4 Participants n=41 Participants	0 Participants n=35 Participants	5 Participants n=31 Participants
Region of Enrollment United States	44 participants n=39 Participants	41 participants n=41 Participants	31 participants n=35 Participants	116 participants n=31 Participants

PRIMARY outcome

Timeframe: Day 0 tilmanocept injection followed by imaging at 60 minutes (60A) and 75 minutes (60B) and at 180 minutes (180A) and 195 minutes (180B).

Population: Planned interim analysis of first 15 subjects in Arms 1 and 2

Outcome measures

Outcome measures
Measure	Subjects Free of Inflammatory Disease n=15 Participants Arm 1 comprised disease-free HCs. Arm 1 evaluated image/re-image consistency (repeatability and stability) of joint-specific and global TUVs across a variety of image acquisition intervals and collect normative HC data. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	RA Subjects on Stable Therapy n=15 Participants Arm 2 comprised clinically diagnosed RA subjects on stable treatment. Arm 2 evaluated image/re-image and test re-test (i.e., repeat dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
Arms 1 & 2: Assess Camera-specific Precision of TUV Left metacarpophalangeal 1, RMSD of TUV at 60 min A vs 60 min B	0.159 Pixel intensity Interval 0.11 to 0.23	0.067 Pixel intensity Interval 0.05 to 0.1
Arms 1 & 2: Assess Camera-specific Precision of TUV Left metacarpophalangeal 2, RMSD of TUV at 60 min A vs 60 min B	0.091 Pixel intensity Interval 0.07 to 0.14	0.124 Pixel intensity Interval 0.09 to 0.19
Arms 1 & 2: Assess Camera-specific Precision of TUV Left metacarpophalangeal 3, RMSD of TUV at 60 min A vs 60 min B	0.087 Pixel intensity Interval 0.06 to 0.13	0.125 Pixel intensity Interval 0.09 to 0.19
Arms 1 & 2: Assess Camera-specific Precision of TUV Left metacarpophalangeal 4, RMSD of TUV at 60 min A vs 60 min B	0.094 Pixel intensity Interval 0.07 to 0.14	0.130 Pixel intensity Interval 0.09 to 0.2
Arms 1 & 2: Assess Camera-specific Precision of TUV Left metacarpophalangeal 5, RMSD of TUV at 60 min A vs 60 min B	0.077 Pixel intensity Interval 0.06 to 0.12	0.070 Pixel intensity Interval 0.05 to 0.09
Arms 1 & 2: Assess Camera-specific Precision of TUV Left proximal interphalangeal 1, RMSD of TUV at 60 min A vs 60 min B	0.078 Pixel intensity Interval 0.05 to 0.11	0.080 Pixel intensity Interval 0.05 to 0.1
Arms 1 & 2: Assess Camera-specific Precision of TUV Left proximal interphalangeal 2, RMSD of TUV at 60 min A vs 60 min B	0.058 Pixel intensity Interval 0.04 to 0.09	0.066 Pixel intensity Interval 0.05 to 0.1
Arms 1 & 2: Assess Camera-specific Precision of TUV Left proximal interphalangeal 3, RMSD of TUV at 60 min A vs 60 min B	0.064 Pixel intensity Interval 0.05 to 0.1	0.099 Pixel intensity Interval 0.07 to 0.14
Arms 1 & 2: Assess Camera-specific Precision of TUV Left proximal interphalangeal 4, RMSD of TUV at 60 min A vs 60 min B	0.080 Pixel intensity Interval 0.06 to 0.12	0.077 Pixel intensity Interval 0.05 to 0.11
Arms 1 & 2: Assess Camera-specific Precision of TUV Left proximal interphalangeal 5, RMSD of TUV at 60 min A vs 60 min B	0.050 Pixel intensity Interval 0.03 to 0.07	0.043 Pixel intensity Interval 0.03 to 0.07
Arms 1 & 2: Assess Camera-specific Precision of TUV Left wrist, RMSD of TUV at 60 min A vs 60 min B	0.089 Pixel intensity Interval 0.06 to 0.13	0.086 Pixel intensity Interval 0.06 to 0.13
Arms 1 & 2: Assess Camera-specific Precision of TUV Right metacarpophalangeal 1, RMSD of TUV at 60 min A vs 60 min B	0.124 Pixel intensity Interval 0.08 to 0.17	0.083 Pixel intensity Interval 0.05 to 0.11
Arms 1 & 2: Assess Camera-specific Precision of TUV Right metacarpophalangeal 2, RMSD of TUV at 60 min A vs 60 min B	0.096 Pixel intensity Interval 0.07 to 0.14	0.165 Pixel intensity Interval 0.12 to 0.25
Arms 1 & 2: Assess Camera-specific Precision of TUV Right metacarpophalangeal 3, RMSD of TUV at 60 min A vs 60 min B	0.097 Pixel intensity Interval 0.07 to 0.15	0.152 Pixel intensity Interval 0.11 to 0.23
Arms 1 & 2: Assess Camera-specific Precision of TUV Right metacarpophalangeal 4, RMSD of TUV at 60 min A vs 60 min B	0.058 Pixel intensity Interval 0.04 to 0.09	0.069 Pixel intensity Interval 0.05 to 0.1
Arms 1 & 2: Assess Camera-specific Precision of TUV Right metacarpophalangeal 5, RMSD of TUV at 60 min A vs 60 min B	0.067 Pixel intensity Interval 0.05 to 0.1	0.062 Pixel intensity Interval 0.05 to 0.1
Arms 1 & 2: Assess Camera-specific Precision of TUV Right proximal interphalangeal 1, RMSD of TUV at 60 min A vs 60 min B	0.090 Pixel intensity Interval 0.06 to 0.14	0.095 Pixel intensity Interval 0.07 to 0.14
Arms 1 & 2: Assess Camera-specific Precision of TUV Right proximal interphalangeal 2, RMSD of TUV at 60 min A vs 60 min B	0.080 Pixel intensity Interval 0.06 to 0.12	0.070 Pixel intensity Interval 0.05 to 0.11
Arms 1 & 2: Assess Camera-specific Precision of TUV Right proximal interphalangeal 3, RMSD of TUV at 60 min A vs 60 min B	0.062 Pixel intensity Interval 0.05 to 0.1	0.059 Pixel intensity Interval 0.04 to 0.09
Arms 1 & 2: Assess Camera-specific Precision of TUV Right proximal interphalangeal 4, RMSD of TUV at 60 min A vs 60 min B	0.084 Pixel intensity Interval 0.06 to 0.12	0.095 Pixel intensity Interval 0.07 to 0.14
Arms 1 & 2: Assess Camera-specific Precision of TUV Right proximal interphalangeal 5, RMSD of TUV at 60 min A vs 60 min B	0.048 Pixel intensity Interval 0.04 to 0.07	0.111 Pixel intensity Interval 0.08 to 0.17
Arms 1 & 2: Assess Camera-specific Precision of TUV Right wrist 5, RMSD of TUV at 60 min A vs 60 min B	0.070 Pixel intensity Interval 0.05 to 0.1	0.097 Pixel intensity Interval 0.07 to 0.15
Arms 1 & 2: Assess Camera-specific Precision of TUV Left metacarpophalangeal 1, RMSD of TUV at 180 min A vs 180 min B	0.119 Pixel intensity Interval 0.09 to 0.18	0.113 Pixel intensity Interval 0.08 to 0.17
Arms 1 & 2: Assess Camera-specific Precision of TUV Left metacarpophalangeal 2, RMSD of TUV at 180 min A vs 180 min B	0.086 Pixel intensity Interval 0.06 to 0.13	0.167 Pixel intensity Interval 0.11 to 0.23
Arms 1 & 2: Assess Camera-specific Precision of TUV Left metacarpophalangeal 3, RMSD of TUV at 180 min A vs 180 min B	0.090 Pixel intensity Interval 0.06 to 0.14	0.097 Pixel intensity Interval 0.07 to 0.14
Arms 1 & 2: Assess Camera-specific Precision of TUV Left metacarpophalangeal 4, RMSD of TUV at 180 min A vs 180 min B	0.110 Pixel intensity Interval 0.07 to 0.14	0.106 Pixel intensity Interval 0.08 to 0.16
Arms 1 & 2: Assess Camera-specific Precision of TUV Left metacarpophalangeal 5, RMSD of TUV at 180 min A vs 180 min B	0.097 Pixel intensity Interval 0.06 to 0.13	0.114 Pixel intensity Interval 0.08 to 0.18
Arms 1 & 2: Assess Camera-specific Precision of TUV Left proximal interphalangeal 1, RMSD of TUV at 180 min A vs 180 min B	0.071 Pixel intensity Interval 0.04 to 0.09	0.106 Pixel intensity Interval 0.08 to 0.16
Arms 1 & 2: Assess Camera-specific Precision of TUV Left proximal interphalangeal 2, RMSD of TUV at 180 min A vs 180 min B	0.050 Pixel intensity Interval 0.03 to 0.07	0.075 Pixel intensity Interval 0.05 to 0.11
Arms 1 & 2: Assess Camera-specific Precision of TUV Left proximal interphalangeal 3, RMSD of TUV at 180 min A vs 180 min B	0.057 Pixel intensity Interval 0.04 to 0.08	0.131 Pixel intensity Interval 0.09 to 0.2
Arms 1 & 2: Assess Camera-specific Precision of TUV Left proximal interphalangeal 4, RMSD of TUV at 180 min A vs 180 min B	0.068 Pixel intensity Interval 0.05 to 0.1	0.083 Pixel intensity Interval 0.06 to 0.13
Arms 1 & 2: Assess Camera-specific Precision of TUV Left proximal interphalangeal 5, RMSD of TUV at 180 min A vs 180 min B	0.077 Pixel intensity Interval 0.05 to 0.1	0.073 Pixel intensity Interval 0.05 to 0.11
Arms 1 & 2: Assess Camera-specific Precision of TUV Left wrist, RMSD of TUV at 180 min A vs 180 min B	0.085 Pixel intensity Interval 0.05 to 0.11	0.137 Pixel intensity Interval 0.09 to 0.18
Arms 1 & 2: Assess Camera-specific Precision of TUV Right metacarpophalangeal 1, RMSD of TUV at 180 min A vs 180 min B	0.079 Pixel intensity Interval 0.06 to 0.12	0.109 Pixel intensity Interval 0.08 to 0.16
Arms 1 & 2: Assess Camera-specific Precision of TUV Right metacarpophalangeal 2, RMSD of TUV at 180 min A vs 180 min B	0.097 Pixel intensity Interval 0.07 to 0.15	0.184 Pixel intensity Interval 0.13 to 0.27
Arms 1 & 2: Assess Camera-specific Precision of TUV Right metacarpophalangeal 3, RMSD of TUV at 180 min A vs 180 min B	0.083 Pixel intensity Interval 0.06 to 0.13	0.138 Pixel intensity Interval 0.1 to 0.2
Arms 1 & 2: Assess Camera-specific Precision of TUV Right metacarpophalangeal 4, RMSD of TUV at 180 min A vs 180 min B	0.103 Pixel intensity Interval 0.07 to 0.14	0.105 Pixel intensity Interval 0.08 to 0.16
Arms 1 & 2: Assess Camera-specific Precision of TUV Right metacarpophalangeal 5, RMSD of TUV at 180 min A vs 180 min B	0.076 Pixel intensity Interval 0.05 to 0.1	0.078 Pixel intensity Interval 0.06 to 0.12
Arms 1 & 2: Assess Camera-specific Precision of TUV Right proximal interphalangeal 1, RMSD of TUV at 180 min A vs 180 min B	0.065 Pixel intensity Interval 0.05 to 0.09	0.107 Pixel intensity Interval 0.07 to 0.14
Arms 1 & 2: Assess Camera-specific Precision of TUV Right proximal interphalangeal 2, RMSD of TUV at 180 min A vs 180 min B	0.086 Pixel intensity Interval 0.06 to 0.13	0.088 Pixel intensity Interval 0.06 to 0.13
Arms 1 & 2: Assess Camera-specific Precision of TUV Right proximal interphalangeal 3, RMSD of TUV at 180 min A vs 180 min B	0.056 Pixel intensity Interval 0.04 to 0.08	0.125 Pixel intensity Interval 0.09 to 0.19
Arms 1 & 2: Assess Camera-specific Precision of TUV Right proximal interphalangeal 4, RMSD of TUV at 180 min A vs 180 min B	0.048 Pixel intensity Interval 0.03 to 0.07	0.099 Pixel intensity Interval 0.07 to 0.15
Arms 1 & 2: Assess Camera-specific Precision of TUV Right wrist, RMSD of TUV at 180 min A vs 180 min B	0.087 Pixel intensity Interval 0.06 to 0.11	0.163 Pixel intensity Interval 0.11 to 0.22

PRIMARY outcome

Timeframe: Day 0 tilmanocept injection followed by imaging at 60 minutes and 180 minutes.

Population: Planned interim analysis of first 15 subjects in Arms 1 and 2

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.

Outcome measures

Outcome measures
Measure	Subjects Free of Inflammatory Disease n=15 Participants Arm 1 comprised disease-free HCs. Arm 1 evaluated image/re-image consistency (repeatability and stability) of joint-specific and global TUVs across a variety of image acquisition intervals and collect normative HC data. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	RA Subjects on Stable Therapy n=15 Participants Arm 2 comprised clinically diagnosed RA subjects on stable treatment. Arm 2 evaluated image/re-image and test re-test (i.e., repeat dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
Arms 1 and 2: Stability of the Mean/Variance Relationship Global TUV at 60 min	263.31 Coefficient of variation	208.79 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left metacarpophalangeal 1 TUV at 60 min	16.92295 Coefficient of variation	13.189704 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left metacarpophalangeal 2 TUV at 60 min	19.613096 Coefficient of variation	20.477108 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left metacarpophalangeal 3 TUV at 60 min	18.651035 Coefficient of variation	16.378147 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left metacarpophalangeal 4 TUV at 60 min	18.511573 Coefficient of variation	13.970308 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left metacarpophalangeal 5 TUV at 60 min	21.20135 Coefficient of variation	12.21378 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left proximal interphalangeal 1 TUV at 60 min	12.819593 Coefficient of variation	11.370952 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left proximal interphalangeal 2 TUV at 60 min	17.553684 Coefficient of variation	9.7087077 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left proximal interphalangeal 3 TUV at 60 min	17.847881 Coefficient of variation	12.604637 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left proximal interphalangeal 4 TUV at 60 min	17.407371 Coefficient of variation	15.660407 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left proximal interphalangeal 5 TUV at 60 min	14.424961 Coefficient of variation	10.066291 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left wrist TUV at 60 min	14.401304 Coefficient of variation	8.7901247 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right metacarpophalangeal 1 TUV at 60 min	13.628956 Coefficient of variation	11.48462 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right metacarpophalangeal 2 TUV at 60 min	19.774959 Coefficient of variation	18.014491 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right metacarpophalangeal 3 TUV at 60 min	20.228576 Coefficient of variation	23.49369 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right metacarpophalangeal 4 TUV at 60 min	18.728588 Coefficient of variation	18.207621 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right metacarpophalangeal 5 TUV at 60 min	19.283062 Coefficient of variation	12.958136 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right proximal interphalangeal 1 TUV at 60 min	14.308134 Coefficient of variation	11.080537 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right proximal interphalangeal 2 TUV at 60 min	18.710387 Coefficient of variation	12.508548 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right proximal interphalangeal 3 TUV at 60 min	14.969821 Coefficient of variation	12.831644 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right proximal interphalangeal 4 TUV at 60 min	18.369256 Coefficient of variation	16.271218 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right proximal interphalangeal 5 TUV at 60 min	18.873772 Coefficient of variation	16.805949 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right wrist TUV at 60 min	13.05914 Coefficient of variation	10.202857 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Global TUV at 180 min	355.82 Coefficient of variation	287.80 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left metacarpophalangeal 1 TUV at 180 min	19.4363 Coefficient of variation	12.081512 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left metacarpophalangeal 2 TUV at 180 min	21.914899 Coefficient of variation	19.814146 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left metacarpophalangeal 3 TUV at 180 min	24.269644 Coefficient of variation	15.786226 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left metacarpophalangeal 4 TUV at 180 min	23.438328 Coefficient of variation	17.776583 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left metacarpophalangeal 5 TUV at 180 min	21.045602 Coefficient of variation	14.647724 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left proximal interphalangeal 1 TUV at 180 min	18.335106 Coefficient of variation	15.40672 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left proximal interphalangeal 2 TUV at 180 min	19.144279 Coefficient of variation	10.324402 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left proximal interphalangeal 3 TUV at 180 min	16.707115 Coefficient of variation	11.347808 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left proximal interphalangeal 4 TUV at 180 min	20.968296 Coefficient of variation	11.384086 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left proximal interphalangeal 5 TUV at 180 min	15.155009 Coefficient of variation	12.16714 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Left wrist TUV at 180 min	17.46611 Coefficient of variation	10.10065 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right metacarpophalangeal 1 TUV at 180 min	18.333323 Coefficient of variation	12.726762 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right metacarpophalangeal 2 TUV at 180 min	19.876281 Coefficient of variation	16.017255 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right metacarpophalangeal 3 TUV at 180 min	19.314268 Coefficient of variation	19.791295 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right metacarpophalangeal 4 TUV at 180 min	21.176376 Coefficient of variation	18.332795 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right metacarpophalangeal 5 TUV at 180 min	21.480266 Coefficient of variation	13.444692 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right proximal interphalangeal 1 TUV at 180 min	16.290041 Coefficient of variation	10.408102 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right proximal interphalangeal 2 TUV at 180 min	18.330801 Coefficient of variation	11.916304 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right proximal interphalangeal 3 TUV at 180 min	17.515896 Coefficient of variation	10.748883 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right proximal interphalangeal 4 TUV at 180 min	20.621393 Coefficient of variation	16.172441 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right proximal interphalangeal 5 TUV at 180 min	18.927298 Coefficient of variation	14.872591 Coefficient of variation
Arms 1 and 2: Stability of the Mean/Variance Relationship Right wrist TUV at 180 min	16.823037 Coefficient of variation	10.559086 Coefficient of variation

PRIMARY outcome

Timeframe: 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.

Population: All Arm 3 subjects with data at the specified timepoint (Week 12 or Week 24)

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)

Outcome measures

Outcome measures
Measure	Subjects Free of Inflammatory Disease n=29 Participants Arm 1 comprised disease-free HCs. Arm 1 evaluated image/re-image consistency (repeatability and stability) of joint-specific and global TUVs across a variety of image acquisition intervals and collect normative HC data. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	RA Subjects on Stable Therapy Arm 2 comprised clinically diagnosed RA subjects on stable treatment. Arm 2 evaluated image/re-image and test re-test (i.e., repeat dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔCDAI12w (overall) - Reader 1	0.248 Kendall rank correlation Interval 0.003 to 0.494	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔCDAI12w (overall) - Reader 2	0.238 Kendall rank correlation Interval 0.002 to 0.474	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔCDAI24w (overall) - Reader 1	0.115 Kendall rank correlation Interval -0.221 to 0.452	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔCDAI24w (overall) - Reader 2	0.121 Kendall rank correlation Interval -0.207 to 0.449	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR12w (Swollen Joint Count) - Reader 1	0.165 Kendall rank correlation Interval -0.077 to 0.407	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR12w (Swollen Joint Count) - Reader 2	0.154 Kendall rank correlation Interval -0.096 to 0.405	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ACR24w (Swollen Joint Count) - Reader 1	0.226 Kendall rank correlation Interval -0.024 to 0.476	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR24w (Swollen Joint Count) - Reader 2	0.235 Kendall rank correlation Interval -0.013 to 0.483	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR12w (Tender Joint Count) - Reader 1	0.119 Kendall rank correlation Interval -0.152 to 0.389	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR12w (Tender Joint Count) - Reader 2	0.138 Kendall rank correlation Interval -0.124 to 0.399	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR24w (Tender Joint Count) - Reader 1	0.161 Kendall rank correlation Interval -0.146 to 0.469	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR24w (Tender Joint Count) - Reader 2	0.194 Kendall rank correlation Interval -0.11 to 0.499	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR12w (ESR) - Reader 1	-0.199 Kendall rank correlation Interval -0.506 to 0.107	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR12w (ESR) - Reader 2	-0.110 Kendall rank correlation Interval -0.412 to 0.192	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR24w (ESR) - Reader 1	-0.267 Kendall rank correlation Interval -0.588 to 0.053	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR24w (ESR) - Reader 2	-0.186 Kendall rank correlation Interval -0.493 to 0.121	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR12w (VAS Pain Scale) - Reader 1	0.110 Kendall rank correlation Interval -0.153 to 0.374	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR12w (VAS Pain Scale) - Reader 2	0.105 Kendall rank correlation Interval -0.153 to 0.362	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR24w (VAS Pain Scale) - Reader 1	-0.125 Kendall rank correlation Interval -0.447 to 0.197	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR24w (VAS Pain Scale) - Reader 2	-0.121 Kendall rank correlation Interval -0.433 to 0.19	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR12w (Patient's Global Assessment) - Reader 1	0.299 Kendall rank correlation Interval 0.108 to 0.49	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR12w (Patient's Global Assessment) - Reader 2	0.261 Kendall rank correlation Interval 0.037 to 0.484	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR24w (Patient's Global Assessment) - Reader 1	0.051 Kendall rank correlation Interval -0.257 to 0.359	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR24w (Patient's Global Assessment) - Reader 2	0.070 Kendall rank correlation Interval -0.226 to 0.366	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR12w (Physician's Global Assessment) - Reader 1	0.137 Kendall rank correlation Interval -0.09 to 0.365	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR12w (Physician's Global Assessment) - Reader 2	0.115 Kendall rank correlation Interval -0.117 to 0.348	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR24w (Physician's Global Assessment) - Reader 1	-0.057 Kendall rank correlation Interval -0.349 to 0.234	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR24w (Physician's Global Assessment) - Reader 2	-0.032 Kendall rank correlation Interval -0.323 to 0.259	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR12w (HAQ-DI Score) - Reader 1	0.025 Kendall rank correlation Interval -0.237 to 0.286	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR12w (HAQ-DI Score) - Reader 2	0.083 Kendall rank correlation Interval -0.167 to 0.333	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR24w (HAQ-DI Score) - Reader 1	-0.032 Kendall rank correlation Interval -0.339 to 0.276	—
Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy ΔTUVglobal[5w] and ΔACR24w (HAQ-DI Score) - Reader 2	0.051 Kendall rank correlation Interval -0.227 to 0.329	—

PRIMARY outcome

Timeframe: Imaging (60 minutes after tilmanocept injection) on Day 0 and Day 8

Population: All Arm 2 subjects with evaluable images at Days 0 and 8

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

Outcome measures

Outcome measures
Measure	Subjects Free of Inflammatory Disease n=35 Participants Arm 1 comprised disease-free HCs. Arm 1 evaluated image/re-image consistency (repeatability and stability) of joint-specific and global TUVs across a variety of image acquisition intervals and collect normative HC data. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	RA Subjects on Stable Therapy Arm 2 comprised clinically diagnosed RA subjects on stable treatment. Arm 2 evaluated image/re-image and test re-test (i.e., repeat dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.183 Pixel intensity Interval 0.147 to 0.237	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.135 Pixel intensity Interval 0.109 to 0.175	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.151 Pixel intensity Interval 0.122 to 0.196	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.221 Pixel intensity Interval 0.174 to 0.28	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.179 Pixel intensity Interval 0.145 to 0.234	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.235 Pixel intensity Interval 0.186 to 0.299	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.263 Pixel intensity Interval 0.213 to 0.342	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.198 Pixel intensity Interval 0.16 to 0.257	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.172 Pixel intensity Interval 0.139 to 0.224	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.229 Pixel intensity Interval 0.185 to 0.298	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.233 Pixel intensity Interval 0.181 to 0.291	—
Longitudinal (8-day) Variation of TUV Left wrist, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.107 Pixel intensity Interval 0.084 to 0.135	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.142 Pixel intensity Interval 0.115 to 0.185	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.134 Pixel intensity Interval 0.109 to 0.175	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.131 Pixel intensity Interval 0.106 to 0.171	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.208 Pixel intensity Interval 0.167 to 0.268	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.213 Pixel intensity Interval 0.167 to 0.269	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.221 Pixel intensity Interval 0.176 to 0.283	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.227 Pixel intensity Interval 0.182 to 0.292	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.212 Pixel intensity Interval 0.169 to 0.271	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.261 Pixel intensity Interval 0.206 to 0.332	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.244 Pixel intensity Interval 0.196 to 0.315	—
Longitudinal (8-day) Variation of TUV Right wrist, RMSD of TUV at Day 0 vs Day 8, Reader 1, Anterior view	0.078 Pixel intensity Interval 0.063 to 0.102	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.180 Pixel intensity Interval 0.137 to 0.219	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.170 Pixel intensity Interval 0.137 to 0.221	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.148 Pixel intensity Interval 0.119 to 0.191	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.130 Pixel intensity Interval 0.104 to 0.168	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.180 Pixel intensity Interval 0.142 to 0.228	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.346 Pixel intensity Interval 0.277 to 0.445	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.245 Pixel intensity Interval 0.198 to 0.318	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.160 Pixel intensity Interval 0.129 to 0.208	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.202 Pixel intensity Interval 0.163 to 0.262	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.242 Pixel intensity Interval 0.193 to 0.31	—
Longitudinal (8-day) Variation of TUV Left wrist, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.106 Pixel intensity Interval 0.079 to 0.126	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.137 Pixel intensity Interval 0.109 to 0.175	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.120 Pixel intensity Interval 0.096 to 0.154	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.124 Pixel intensity Interval 0.099 to 0.16	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.159 Pixel intensity Interval 0.128 to 0.206	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.165 Pixel intensity Interval 0.133 to 0.213	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.237 Pixel intensity Interval 0.192 to 0.309	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.172 Pixel intensity Interval 0.138 to 0.222	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.219 Pixel intensity Interval 0.178 to 0.286	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.271 Pixel intensity Interval 0.215 to 0.345	—
Longitudinal (8-day) Variation of TUV Right wrist, RMSD of TUV at Day 0 vs Day 8, Reader 2, Anterior view	0.084 Pixel intensity Interval 0.062 to 0.098	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.251 Pixel intensity Interval 0.203 to 0.326	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.229 Pixel intensity Interval 0.182 to 0.293	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.225 Pixel intensity Interval 0.18 to 0.29	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.224 Pixel intensity Interval 0.182 to 0.292	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.357 Pixel intensity Interval 0.289 to 0.465	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.303 Pixel intensity Interval 0.245 to 0.395	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.254 Pixel intensity Interval 0.199 to 0.321	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.251 Pixel intensity Interval 0.203 to 0.326	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.240 Pixel intensity Interval 0.187 to 0.3	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.313 Pixel intensity Interval 0.254 to 0.408	—
Longitudinal (8-day) Variation of TUV Left wrist, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.180 Pixel intensity Interval 0.146 to 0.234	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.288 Pixel intensity Interval 0.233 to 0.375	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.214 Pixel intensity Interval 0.173 to 0.278	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.143 Pixel intensity Interval 0.114 to 0.183	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.188 Pixel intensity Interval 0.149 to 0.239	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.247 Pixel intensity Interval 0.195 to 0.314	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.307 Pixel intensity Interval 0.249 to 0.4	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.253 Pixel intensity Interval 0.204 to 0.328	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.221 Pixel intensity Interval 0.178 to 0.286	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.246 Pixel intensity Interval 0.2 to 0.321	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.367 Pixel intensity Interval 0.297 to 0.477	—
Longitudinal (8-day) Variation of TUV Right wrist, RMSD of TUV at Day 0 vs Day 8, Reader 1, Posterior view	0.133 Pixel intensity Interval 0.108 to 0.173	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.112 Pixel intensity Interval 0.087 to 0.139	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.112 Pixel intensity Interval 0.09 to 0.144	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.105 Pixel intensity Interval 0.085 to 0.136	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.109 Pixel intensity Interval 0.088 to 0.142	—
Longitudinal (8-day) Variation of TUV Left metacarpophalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.152 Pixel intensity Interval 0.123 to 0.198	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.227 Pixel intensity Interval 0.18 to 0.29	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.133 Pixel intensity Interval 0.108 to 0.173	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.205 Pixel intensity Interval 0.161 to 0.259	—
Longitudinal (8-day) Variation of TUV Left proximal interphalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.281 Pixel intensity Interval 0.221 to 0.356	—
Longitudinal (8-day) Variation of TUV Left wrist, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.081 Pixel intensity Interval 0.062 to 0.099	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.149 Pixel intensity Interval 0.12 to 0.194	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.141 Pixel intensity Interval 0.111 to 0.179	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.132 Pixel intensity Interval 0.107 to 0.173	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.137 Pixel intensity Interval 0.109 to 0.175	—
Longitudinal (8-day) Variation of TUV Right metacarpophalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.165 Pixel intensity Interval 0.134 to 0.215	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 1, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	1.834 Pixel intensity Interval 1.471 to 2.365	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 2, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.178 Pixel intensity Interval 0.144 to 0.231	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 3, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.199 Pixel intensity Interval 0.16 to 0.257	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 4, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.200 Pixel intensity Interval 0.162 to 0.26	—
Longitudinal (8-day) Variation of TUV Right proximal interphalangeal 5, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.215 Pixel intensity Interval 0.174 to 0.279	—
Longitudinal (8-day) Variation of TUV Right wrist, RMSD of TUV at Day 0 vs Day 8, Reader 2, Posterior view	0.081 Pixel intensity Interval 0.065 to 0.104	—

SECONDARY outcome

Timeframe: Images obtained 60 minutes after tilmanocept injection on Day 0.

Population: Healthy control subjects with evaluable scans. Unevaluable scans included those with poor hand placement/positioning and low signal (overlapping with background) in most of the fingers.

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)

Outcome measures

Outcome measures
Measure	Subjects Free of Inflammatory Disease n=29 Participants Arm 1 comprised disease-free HCs. Arm 1 evaluated image/re-image consistency (repeatability and stability) of joint-specific and global TUVs across a variety of image acquisition intervals and collect normative HC data. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	RA Subjects on Stable Therapy Arm 2 comprised clinically diagnosed RA subjects on stable treatment. Arm 2 evaluated image/re-image and test re-test (i.e., repeat dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 1, Anterior View, Reader 1	1.01 Pixel intensity Standard Deviation 0.213	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 1, Anterior View, Reader 2	1.20 Pixel intensity Standard Deviation 0.257	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 1, Posterior View, Reader 1	1.05 Pixel intensity Standard Deviation 0.185	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 1, Posterior View, Reader 2	1.33 Pixel intensity Standard Deviation 0.200	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 2, Anterior View, Reader 1	0.85 Pixel intensity Standard Deviation 0.169	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 2, Anterior View, Reader 2	0.92 Pixel intensity Standard Deviation 0.180	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 2, Posterior View, Reader 1	0.86 Pixel intensity Standard Deviation 0.158	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 2, Posterior View, Reader 2	1.00 Pixel intensity Standard Deviation 0.170	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 3, Anterior View, Reader 1	0.79 Pixel intensity Standard Deviation 0.158	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 3, Anterior View, Reader 2	0.90 Pixel intensity Standard Deviation 0.197	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 3, Posterior View, Reader 1	0.86 Pixel intensity Standard Deviation 0.186	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 3, Posterior View, Reader 2	1.04 Pixel intensity Standard Deviation 0.174	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 4, Anterior View, Reader 1	0.77 Pixel intensity Standard Deviation 0.192	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 4, Anterior View, Reader 2	0.90 Pixel intensity Standard Deviation 0.201	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 4, Posterior View, Reader 1	0.80 Pixel intensity Standard Deviation 0.144	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 4, Posterior View, Reader 2	1.01 Pixel intensity Standard Deviation 0.161	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 5, Anterior View, Reader 1	0.73 Pixel intensity Standard Deviation 0.186	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 5, Anterior View, Reader 2	0.82 Pixel intensity Standard Deviation 0.189	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 5, Posterior View, Reader 1	0.80 Pixel intensity Standard Deviation 0.162	—
Arm 1 Normal Ranges of TUVjoint Left Metacarpophalangeal 5, Posterior View, Reader 2	0.92 Pixel intensity Standard Deviation 0.169	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 1, Anterior View, Reader 1	0.75 Pixel intensity Standard Deviation 0.158	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 1, Anterior View, Reader 2	0.89 Pixel intensity Standard Deviation 0.192	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 1, Posterior View, Reader 1	0.79 Pixel intensity Standard Deviation 0.175	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 1, Posterior View, Reader 2	0.93 Pixel intensity Standard Deviation 0.166	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 2, Anterior View, Reader 1	0.71 Pixel intensity Standard Deviation 0.170	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 2, Anterior View, Reader 2	0.77 Pixel intensity Standard Deviation 0.179	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 2, Posterior View, Reader 1	0.68 Pixel intensity Standard Deviation 0.129	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 2, Posterior View, Reader 2	0.79 Pixel intensity Standard Deviation 0.155	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 3, Anterior View, Reader 1	0.70 Pixel intensity Standard Deviation 0.184	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 3, Anterior View, Reader 2	0.73 Pixel intensity Standard Deviation 0.192	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 3, Posterior View, Reader 1	0.69 Pixel intensity Standard Deviation 0.126	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 3, Posterior View, Reader 2	0.82 Pixel intensity Standard Deviation 0.146	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 4, Anterior View, Reader 1	0.66 Pixel intensity Standard Deviation 0.143	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 4, Anterior View, Reader 2	0.72 Pixel intensity Standard Deviation 0.167	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 4, Posterior View, Reader 1	0.64 Pixel intensity Standard Deviation 0.128	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 4, Posterior View, Reader 2	0.75 Pixel intensity Standard Deviation 0.156	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 5, Anterior View, Reader 1	0.59 Pixel intensity Standard Deviation 0.147	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 5, Anterior View, Reader 2	0.66 Pixel intensity Standard Deviation 0.141	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 5, Posterior View, Reader 1	0.59 Pixel intensity Standard Deviation 0.124	—
Arm 1 Normal Ranges of TUVjoint Left Proximal Interphalangeal 5, Posterior View, Reader 2	0.69 Pixel intensity Standard Deviation 0.135	—
Arm 1 Normal Ranges of TUVjoint Left Wrist, Anterior View, Reader 1	1.32 Pixel intensity Standard Deviation 0.229	—
Arm 1 Normal Ranges of TUVjoint Left Wrist, Anterior View, Reader 2	1.48 Pixel intensity Standard Deviation 0.243	—
Arm 1 Normal Ranges of TUVjoint Left Wrist, Posterior View, Reader 1	1.40 Pixel intensity Standard Deviation 0.183	—
Arm 1 Normal Ranges of TUVjoint Left Wrist, Posterior View, Reader 2	1.66 Pixel intensity Standard Deviation 0.180	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 1, Anterior View, Reader 1	0.98 Pixel intensity Standard Deviation 0.185	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 1, Anterior View, Reader 2	1.17 Pixel intensity Standard Deviation 0.244	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 1, Posterior View, Reader 1	1.04 Pixel intensity Standard Deviation 0.190	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 1, Posterior View, Reader 2	1.29 Pixel intensity Standard Deviation 0.297	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 2, Anterior View, Reader 1	0.87 Pixel intensity Standard Deviation 0.180	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 2, Anterior View, Reader 2	0.88 Pixel intensity Standard Deviation 0.181	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 2, Posterior View, Reader 1	0.94 Pixel intensity Standard Deviation 0.206	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 2, Posterior View, Reader 2	1.00 Pixel intensity Standard Deviation 0.182	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 3, Anterior View, Reader 1	0.83 Pixel intensity Standard Deviation 0.176	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 3, Anterior View, Reader 2	0.91 Pixel intensity Standard Deviation 0.191	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 3, Posterior View, Reader 1	0.86 Pixel intensity Standard Deviation 0.143	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 3, Posterior View, Reader 2	1.02 Pixel intensity Standard Deviation 0.189	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 4, Anterior View, Reader 1	0.83 Pixel intensity Standard Deviation 0.214	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 4, Anterior View, Reader 2	0.94 Pixel intensity Standard Deviation 0.216	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 4, Posterior View, Reader 1	0.83 Pixel intensity Standard Deviation 0.141	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 4, Posterior View, Reader 2	1.02 Pixel intensity Standard Deviation 0.199	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 5, Anterior View, Reader 1	0.74 Pixel intensity Standard Deviation 0.174	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 5, Anterior View, Reader 2	0.86 Pixel intensity Standard Deviation 0.212	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 5, Posterior View, Reader 1	0.78 Pixel intensity Standard Deviation 0.156	—
Arm 1 Normal Ranges of TUVjoint Right Metacarpophalangeal 5, Posterior View, Reader 2	0.96 Pixel intensity Standard Deviation 0.200	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 1, Anterior View, Reader 1	0.79 Pixel intensity Standard Deviation 0.162	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 1, Anterior View, Reader 2	0.89 Pixel intensity Standard Deviation 0.198	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 1, Posterior View, Reader 1	0.80 Pixel intensity Standard Deviation 0.161	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 1, Posterior View, Reader 2	0.95 Pixel intensity Standard Deviation 0.155	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 2, Anterior View, Reader 1	0.68 Pixel intensity Standard Deviation 0.140	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 2, Anterior View, Reader 2	0.75 Pixel intensity Standard Deviation 0.159	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 2, Posterior View, Reader 1	0.73 Pixel intensity Standard Deviation 0.114	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 2, Posterior View, Reader 2	0.79 Pixel intensity Standard Deviation 0.129	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 3, Anterior View, Reader 1	0.66 Pixel intensity Standard Deviation 0.164	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 3, Anterior View, Reader 2	0.73 Pixel intensity Standard Deviation 0.183	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 3, Posterior View, Reader 1	0.71 Pixel intensity Standard Deviation 0.118	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 3, Posterior View, Reader 2	0.80 Pixel intensity Standard Deviation 0.139	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 4, Anterior View, Reader 1	0.67 Pixel intensity Standard Deviation 0.196	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 4, Anterior View, Reader 2	0.73 Pixel intensity Standard Deviation 0.172	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 4, Posterior View, Reader 1	0.65 Pixel intensity Standard Deviation 0.132	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 4, Posterior View, Reader 2	0.73 Pixel intensity Standard Deviation 0.142	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 5, Anterior View, Reader 1	0.58 Pixel intensity Standard Deviation 0.141	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 5, Anterior View, Reader 2	0.66 Pixel intensity Standard Deviation 0.135	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 5, Posterior View, Reader 1	0.55 Pixel intensity Standard Deviation 0.093	—
Arm 1 Normal Ranges of TUVjoint Right Proximal Interphalangeal 5, Posterior View, Reader 2	0.66 Pixel intensity Standard Deviation 0.122	—
Arm 1 Normal Ranges of TUVjoint Right Wrist, Anterior View, Reader 1	1.35 Pixel intensity Standard Deviation 0.221	—
Arm 1 Normal Ranges of TUVjoint Right Wrist, Anterior View, Reader 2	1.51 Pixel intensity Standard Deviation 0.253	—
Arm 1 Normal Ranges of TUVjoint Right Wrist, Posterior View, Reader 1	1.41 Pixel intensity Standard Deviation 0.188	—
Arm 1 Normal Ranges of TUVjoint Right Wrist, Posterior View, Reader 2	1.65 Pixel intensity Standard Deviation 0.264	—

SECONDARY outcome

Timeframe: A SPECT/CT scan was performed at approximately 210 minutes after the tilmanocept injection on Day 8 of the trial.

Population: All Arm 2 subjects who received SPECT/CT scan

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

Outcome measures

Outcome measures
Measure	Subjects Free of Inflammatory Disease n=20 Participants Arm 1 comprised disease-free HCs. Arm 1 evaluated image/re-image consistency (repeatability and stability) of joint-specific and global TUVs across a variety of image acquisition intervals and collect normative HC data. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	RA Subjects on Stable Therapy Arm 2 comprised clinically diagnosed RA subjects on stable treatment. Arm 2 evaluated image/re-image and test re-test (i.e., repeat dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
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	0 Percent of participants	—

SECONDARY outcome

Timeframe: 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.

Population: All Arm 3 subjects with data at the specified timepoint (Week 12 or Week 24)

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).

Outcome measures

Outcome measures
Measure	Subjects Free of Inflammatory Disease n=29 Participants Arm 1 comprised disease-free HCs. Arm 1 evaluated image/re-image consistency (repeatability and stability) of joint-specific and global TUVs across a variety of image acquisition intervals and collect normative HC data. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	RA Subjects on Stable Therapy Arm 2 comprised clinically diagnosed RA subjects on stable treatment. Arm 2 evaluated image/re-image and test re-test (i.e., repeat dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals. TC99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔCDAI12w (overall) - Reader 1	-0.045 Kendall rank correlation Interval -0.32 to 0.229	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔCDAI24w (overall) - Reader 1	0.072 Kendall rank correlation Interval -0.215 to 0.359	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR12w (Swollen Joint Count) - Reader 1	-0.100 Kendall rank correlation Interval -0.387 to 0.186	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR24w (Swollen Joint Count) - Reader 1	-0.067 Kendall rank correlation Interval -0.391 to 0.258	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR12w (Tender Joint Count) - Reader 1	-0.086 Kendall rank correlation Interval -0.317 to 0.144	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR24w (Tender Joint Count) - Reader 1	0.130 Kendall rank correlation Interval -0.171 to 0.43	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR12w (ESR) - Reader 1	-0.176 Kendall rank correlation Interval -0.473 to 0.12	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR24w (ESR) - Reader 1	-0.261 Kendall rank correlation Interval -0.471 to -0.051	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR12w (VAS Pain Scale) - Reader 1	-0.099 Kendall rank correlation Interval -0.292 to 0.093	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR24w (VAS Pain Scale) - Reader 1	-0.062 Kendall rank correlation Interval -0.303 to 0.178	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR12w (Patient's Global Assessment) - Reader 1	-0.096 Kendall rank correlation Interval -0.393 to 0.201	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR24w (Patient's Global Assessment) - Reader 1	-0.070 Kendall rank correlation Interval -0.323 to 0.183	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR12w (Physician's Global Assessment) - Reader 1	0.121 Kendall rank correlation Interval -0.212 to 0.454	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR24w (Physician's Global Assessment) - Reader 1	0.057 Kendall rank correlation Interval -0.254 to 0.369	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔCDAI12w (overall) - Reader 2	-0.029 Kendall rank correlation Interval -0.299 to 0.241	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔCDAI24w (overall) - Reader 2	0.109 Kendall rank correlation Interval -0.176 to 0.393	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR12w (Swollen Joint Count) - Reader 2	-0.073 Kendall rank correlation Interval -0.356 to 0.21	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR24w (Swollen Joint Count) - Reader 2	-0.025 Kendall rank correlation Interval -0.349 to 0.298	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR12w (Tender Joint Count) - Reader 2	-0.057 Kendall rank correlation Interval -0.298 to 0.184	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR24w (Tender Joint Count) - Reader 2	0.175 Kendall rank correlation Interval -0.131 to 0.482	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR12w (ESR) - Reader 2	-0.145 Kendall rank correlation Interval -0.454 to 0.165	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR24w (ESR) - Reader 2	-0.234 Kendall rank correlation Interval -0.468 to 0.001	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR12w (VAS Pain Scale) - Reader 2	-0.110 Kendall rank correlation Interval -0.303 to 0.083	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR24w (VAS Pain Scale) - Reader 2	-0.028 Kendall rank correlation Interval -0.263 to 0.207	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR12w (Patient's Global Assessment) - Reader 2	-0.096 Kendall rank correlation Interval -0.384 to 0.192	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR24w (Patient's Global Assessment) - Reader 2	-0.038 Kendall rank correlation Interval -0.295 to 0.219	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR12w (Physician's Global Assessment) - Reader 2	0.110 Kendall rank correlation Interval -0.223 to 0.443	—
Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) TUVglobal[baseline] and ΔACR24w (Physician's Global Assessment) - Reader 2	0.064 Kendall rank correlation Interval -0.251 to 0.379	—

Adverse Events

Subjects Free of Inflammatory Disease

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

RA Subjects on Stable Therapy

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

RA Subjects Who Are Candidates for Initiation of a New Anti-TNFα Therapy

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Subjects Free of Inflammatory Disease n=44 participants at risk Arm 1 included inflammatory-disease-free HCs. Arm 1 evaluated image/re-image consistency (repeatability and stability) of joint-specific and global TUVs across a variety of image acquisition intervals and collect normative HC data. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	RA Subjects on Stable Therapy n=41 participants at risk Arm 2 included clinically diagnosed RA subjects on stable treatment. Arm 2 evaluated image/re-image and test re-test (i.e., repeat dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	RA Subjects Who Are Candidates for Initiation of a New Anti-TNFα Therapy n=31 participants at risk Arm 3 included clinically diagnosed RA subjects on stable treatment who were candidates for new anti-TNFα therapy. Arm 3 assessed the efficacy of global TUVs, obtained before and after initiation of a new anti-TNFα therapy, to predict future clinical responsiveness to the new therapy. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
Cardiac disorders Acute coronary syndrome	0.00% 0/44 • Untoward medical events beginning on Visit 2 (Day 0) until the final visit (variable per arm) were reported as adverse events. For subjects in Arms 1 and 2, the final visit (Visit 5) occurred on Day 8 to 12. For subjects in Arm 3, the final visit (Visit 9) occurred on Week 24 to 26.	0.00% 0/41 • Untoward medical events beginning on Visit 2 (Day 0) until the final visit (variable per arm) were reported as adverse events. For subjects in Arms 1 and 2, the final visit (Visit 5) occurred on Day 8 to 12. For subjects in Arm 3, the final visit (Visit 9) occurred on Week 24 to 26.	3.2% 1/31 • Number of events 1 • Untoward medical events beginning on Visit 2 (Day 0) until the final visit (variable per arm) were reported as adverse events. For subjects in Arms 1 and 2, the final visit (Visit 5) occurred on Day 8 to 12. For subjects in Arm 3, the final visit (Visit 9) occurred on Week 24 to 26.
Cardiac disorders Acute myocardial infarction	0.00% 0/44 • Untoward medical events beginning on Visit 2 (Day 0) until the final visit (variable per arm) were reported as adverse events. For subjects in Arms 1 and 2, the final visit (Visit 5) occurred on Day 8 to 12. For subjects in Arm 3, the final visit (Visit 9) occurred on Week 24 to 26.	0.00% 0/41 • Untoward medical events beginning on Visit 2 (Day 0) until the final visit (variable per arm) were reported as adverse events. For subjects in Arms 1 and 2, the final visit (Visit 5) occurred on Day 8 to 12. For subjects in Arm 3, the final visit (Visit 9) occurred on Week 24 to 26.	3.2% 1/31 • Number of events 1 • Untoward medical events beginning on Visit 2 (Day 0) until the final visit (variable per arm) were reported as adverse events. For subjects in Arms 1 and 2, the final visit (Visit 5) occurred on Day 8 to 12. For subjects in Arm 3, the final visit (Visit 9) occurred on Week 24 to 26.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/44 • Untoward medical events beginning on Visit 2 (Day 0) until the final visit (variable per arm) were reported as adverse events. For subjects in Arms 1 and 2, the final visit (Visit 5) occurred on Day 8 to 12. For subjects in Arm 3, the final visit (Visit 9) occurred on Week 24 to 26.	0.00% 0/41 • Untoward medical events beginning on Visit 2 (Day 0) until the final visit (variable per arm) were reported as adverse events. For subjects in Arms 1 and 2, the final visit (Visit 5) occurred on Day 8 to 12. For subjects in Arm 3, the final visit (Visit 9) occurred on Week 24 to 26.	3.2% 1/31 • Number of events 1 • Untoward medical events beginning on Visit 2 (Day 0) until the final visit (variable per arm) were reported as adverse events. For subjects in Arms 1 and 2, the final visit (Visit 5) occurred on Day 8 to 12. For subjects in Arm 3, the final visit (Visit 9) occurred on Week 24 to 26.

Other adverse events

Additional Information

Chief Medical Officer

Navidea Biopharmaceuticals

Phone: 614-822-2320

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place