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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04947137

Enrollment

134

Registered

2021-07-01

Start date

2021-05-27

Completion date

2022-01-21

Last updated

2025-01-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Keywords

RA, Healthy control, Tilmanocept

Brief summary

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

Detailed description

This is a prospective, open-label, multicenter, single-dose study designed to develop a normative database of TUVjoint in HCs and to assess the feasibility of qualitative and quantitative SPECT/CT assessments in HCs and subjects with active RA. This study is stratified into 2 arms. Arm 1 is comprised of HCs and Arm 2 is comprised of HCs and clinically diagnosed RA subjects on stable treatment.

Interventions

DRUGTc99m tilmanocept

Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

DIAGNOSTIC

Masking

NONE

Intervention model description

This is a prospective, open-label, multicenter, single-dose study designed to develop a normative database of TUVjoint in HCs and to assess the feasibility of qualitative and quantitative SPECT/CT assessments in HCs and subjects with active RA. Subjects will be enrolled in 1 of 2 study arms with distinct study procedures in accordance with Arm-specific eligibility requirements.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

ALL SUBJECTS 1. The subject has provided written informed consent with HIPAA (Health Information Portability and Accountability Act) authorization before the initiation of any study-related procedures. 2. The subject has agreed to not engage in any diet, lifestyle, or medication changes until study completion. HEALTHY CONTROL SUBJECTS 3. The subject is 30 years of age or greater at the time of consent. 4. The subject is deemed to be clinically free of any inflammatory disease(s), autoimmune disease(s), or arthropathies and has not experienced joint pain for at least 28 days prior to the consent date. 5. The subject is not currently on anti-inflammatory drugs (including non-steroidal anti-inflammatory drugs \[NSAIDs\]) and has not taken any anti-inflammatories for at least 28 days prior to the consent date. 6. For all ongoing concomitant medications, the subject has maintained a stable dose for at least 28 days prior to the consent date. CLINICALLY DIAGNOSED ACTIVE RA SUBJECTS 3\. The subject is at least 18 years of age and was ≥ 18 years of age at the time of RA diagnosis. 4\. The subject has moderate to severe RA as determined by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria (score of ≥ 6/10). 5\. The subject has a 28-joint disease activity score (DAS28) of ≥ 3.2 (includes the Erythrocyte Sedimentation Rate \[ESR\] test and Visual Analog Scale \[VAS\]). 6\. Subjects receiving traditional DMARDs must have been on therapy for ≥ 90 days and at a stable dose for ≥ 30 days prior to the imaging visit (Day 0). 7. If the subject is receiving bDMARD or janus kinase (JAK) inhibitor therapy, they have been at a stable dose \> 60 days prior to the imaging visit (Day 0). 8. If the subject is receiving NSAIDs or oral corticosteroids, the dose has been stable for ≥ 28 days prior to the imaging visit (Day 0). The corticosteroid dose must be ≤ 10 mg/day of prednisone or an equivalent steroid dose.

Exclusion criteria

1. The subject is pregnant or lactating. 2. The subject size or weight is not compatible with imaging per the investigator. 3. The subject is currently receiving radiation therapy or chemotherapy or has received radiation therapy or chemotherapy in the past six months. 4. The subject has had a finger, hand, and/or wrist amputation or hand or wrist joint arthroplasty. 5. The subject has renal insufficiency as demonstrated by a glomerular filtration rate of \< 60 mL/min. 6. The subject has hepatic insufficiency as demonstrated by ALT (alanine aminotransferase \[SGPT\]) or AST (aspartate aminotransferase \[SGOT\]) greater than 2 times the upper limit of normal. 7. The subject has any severe, acute, or chronic medical conditions and/or psychiatric conditions and/or laboratory abnormalities that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration that would deem the subject inappropriate for study participation or compromise the safety of the subject or the quality of the data. 8. The subject has any unstable medical illnesses, including hepatic, renal, gastroenterologic, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease. 9. The subject has a known allergy to or has had an adverse reaction to dextran exposure. 10. The subject has received an investigational product within 30 days prior to Tc 99m tilmanocept administration (Day 0). 11. The subject has received intra-articular corticosteroid injections ≤ 8 weeks prior to Tc 99m tilmanocept administration (Day 0). 12. The subject has received any radiopharmaceutical within 7 days or 10 half-lives prior to Tc 99m tilmanocept administration (Day 0). 13. Healthy Controls only: The subject has a positive rheumatoid factor and an elevated ESR or CRP.

Design outcomes

Primary

Measure	Time frame	Description
Normal Limits of TUVjoint in Healthy Subjects	Up to 39 days	The normal limits of TUVjoint (on a per joint basis) in HC subjects, which are defined as the 5 and 95 percentiles of TUVjoint of bilateral joints (i.e., bilateral wrists, metacarpophalangeal joint \[MCPs\], proximal interphalangeal \[PIPs\]).
Qualitative Evaluation of SPECT/CT for Tilmanocept Localization	Up to 39 days	Presence/absence of tilmanocept localization in the hands and wrists will be summarized with frequency counts and percentages by reader and joint.

Secondary

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

Other

Measure	Time frame
Safety Objective: To Evaluate Safety Through the Examination of AE Incidence and Changes Over Time in Laboratory Tests, Vital Signs, and Physical Examination Findings.	Up to 39 days

Countries

United States

Participant flow

Participants by arm

Arm	Count
Subjects Free of Inflammatory Disease Arm 1 includes HCs who are deemed to be clinically free of inflammatory diseases, arthropathies, and/or arthroplasties and clinically free of joint pain for at least 28 days prior to the consent date. Tc 99m tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	120
Healthy Controls and RA Subjects on Stable Therapy Arm 2 includes \[1\] disease-free HCs and \[2\] clinically diagnosed RA subjects on stable treatment. Tc 99m tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	14
Total	134

Baseline characteristics

Characteristic	Total	Subjects Free of Inflammatory Disease	Healthy Controls and RA Subjects on Stable Therapy
Age, Continuous	54.9 years	54.9 years	54.8 years
Ethnicity (NIH/OMB) Hispanic or Latino	73 Participants	73 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	61 Participants	47 Participants	14 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) Black or African American	7 Participants	6 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) White	122 Participants	109 Participants	13 Participants
Sex: Female, Male Female	103 Participants	94 Participants	9 Participants
Sex: Female, Male Male	31 Participants	26 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 120	0 / 14
other Total, other adverse events	2 / 120	0 / 14
serious Total, serious adverse events	0 / 120	0 / 14

Outcome results

Primary

Normal Limits of TUVjoint in Healthy Subjects

The normal limits of TUVjoint (on a per joint basis) in HC subjects, which are defined as the 5 and 95 percentiles of TUVjoint of bilateral joints (i.e., bilateral wrists, metacarpophalangeal joint \[MCPs\], proximal interphalangeal \[PIPs\]).

Time frame: Up to 39 days