Tc 99m Tilmanocept Imaging for Early Prediction of Anti-TNFα Therapy Response in Moderate to Severe Active RA

Study Overview
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Brief Summary
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This study will confirm the ability of Tc 99m tilmanocept imaging to predict clinical response in individuals with RA who are beginning anti-TNFα therapy.

Detailed Description
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This is a prospective, open-label, multicenter study designed to evaluate the early predictive capacity of Tc 99m tilmanocept planar imaging for downstream clinical response(s) in individuals with moderate to severe RA who are candidates for change in anti-TNFα therapy. Temporal (Baseline to 5 week) differences in quantitative imaging will be correlated with longitudinal (Baseline to 12- and 24-week) assessments of clinical RA outcomes to evaluate the clinical utility of Tc 99m tilmanocept for the expedited evaluation of antirheumatic treatment efficacy when compared with longitudinal assessments in clinical practice.

Official Title
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Evaluation of Tc 99m Tilmanocept Imaging for the Early Prediction of Anti-TNFα Therapy Response in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA)

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: TC99m-tilmanocept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has provided written informed consent with HIPAA (Health Information Portability and Accountability Act) authorization before the initiation of any study-related procedures. The subject is at least 18 years of age and was ≥ 18 years of age at the time of RA diagnosis. The subject is a candidate for initiation of, or change to, a new anti-TNFα bDMARD therapy. The subject has RA as determined by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria (score of ≥ 6/10). The subject has moderate to severe RA as determined by a 28-joint disease activity score (DAS28) of ≥ 3.2 (includes the Erythrocyte Sedimentation Rate [ESR] test and Visual Analog Scale [VAS]). Subjects receiving traditional DMARDs must have been on therapy for ≥ 90 days and at a stable dose for ≥ 30 days prior to the first imaging visit (Day 0). Subjects receiving bDMARD or janus kinase (JAK) inhibitor therapy must have been at a stable dose > 60 days prior to the first imaging visit (Day 0). If the subject is receiving NSAIDS (nonsteroidal anti-inflammatory drug) or oral corticosteroids, the dose has been stable for > 28 days prior to the first imaging visit (Day 0). The corticosteroid dose must be ≤ 10 mg/day of prednisone or an equivalent steroid dose. Exclusion Criteria: The subject is pregnant or lactating. The subject size or weight is not compatible with imaging per the investigator. The subject is currently receiving radiation therapy or chemotherapy or has received radiation or chemotherapy within the past 5 years. The subject has an active malignancy or a history of malignancy within the past 5 years. The subject has had a finger, hand, and/or wrist amputation or hand or wrist joint arthroplasty. The subject has renal insufficiency as demonstrated by a glomerular filtration rate of < 60 mL/min. The subject has hepatic insufficiency as demonstrated by ALT (alanine aminotransferase [SGPT]) or AST (aspartate aminotransferase [SGOT]) greater than 2 times the upper limit of normal. The subject has any severe, acute, or chronic medical conditions and/or psychiatric conditions and/or laboratory abnormalities that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration that would deem the subject inappropriate for study participation. The subject has a history of hypersensitivity reactions to TNF-inhibitors. The subject has a known allergy to or has had an adverse reaction to dextran exposure. The subject has received an investigational product within 30 days prior to the Tc 99m tilmanocept administration at the first imaging visit (Day 0). The subject has received intra-articular corticosteroid injections ≤ 8 weeks prior to the first imaging visit (Day 0). The subject has received any radiopharmaceutical within 7 days or 10 half-lives prior to the administration of Tc 99m tilmanocept at the first imaging visit (Day 0). The subject has heart failure [New York Heart Association (NYHA) Class III-IV], a demyelinating disorder, or a chronic/latent infection [e.g., +Purified Protein Derivative (PPD) test, Human Immunodeficiency Virus (HIV), Hepatitis B].

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Candidates for initiation of anti-TNFα bDMARD therapy<br>All subjects will be candidates for initiation of, or change to, a new anti-TNFα bDMARD for RA treatment. | Drug: TC99m-tilmanocept<br>* Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.<br>* Other names: Lymphoseek;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Specificity of Tilmanocept Uptake Value (TUV) | Specificity of the change in TUVglobal with bucketing from baseline to 5 weeks after a change in anti-TNFα therapy (ΔTUVglobal[5w] with bucketing) with respect to ACR50 at week 24 after the change in therapy. | Up to 213 days | 
| Sensitivity of Tilmanocept Uptake Value (TUV) | Sensitivity of the change in TUVglobal with bucketing from baseline to 5 weeks after change in anti-TNFα therapy (ΔTUVglobal[5w] with bucketing) with respect to ACR50 at week 24 after the change in therapy. | Up to 213 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Negative predictive value (NPV) of TUV Baseline at Week 24 | NPV of TUV global obtained at baseline (TUVglobal[b]) with respect to ACR50 at week 24 after change in anti-TNFα therapy | Up to 213 days | 
| Sensitivity and specificity of ΔTUVglobal[5w] with bucketing with respect to ACR50 at Week 12 | Concordance of ΔTUVglobal[5w] with bucketing and ACR50 at week 12, evaluated using sensitivity and specificity. | Up to 213 days | 
| NPV, and PPV, and OA of ΔTUVglobal[5w] with bucketing with respect to ACR50 at Weeks 12 and 24 | Concordance of ΔTUVglobal[5w] (with bucketing) and clinical criteria, including ACR Response Criteria, CDAI, DAS28, and HAQ-DI©. Concordance between ΔTUVglobal[5w] and the clinical criteria will be evaluated using NPV, PPV and overall accuracy. | up to 213 days | 
| Negative predictive value (NPV) of TUV Baseline at Week 12 | Negative predictive value (NPV) of TUVglobal obtained at baseline (TUVglobal[b]) with respect to ACR50 at week 12 | up to 213 days | 
| Concordance of TUV Baseline and Change in Clinical Disease Activity Index (CDAI), 28-joint count Disease Activity Score (DAS28), and American College of Rheumatology (ACR) Response Criteria | TUVglobal[b] 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, by the CFB of DAS28 to 12 +/- 1 weeks and 24 +/- 1 weeks and by the CFB in each of the ACR Response Criteria components at 12 +/- 1 weeks and at 24 +/- 1 weeks. | Up to 213 days | 
| Concordance of TUV Baseline to Week 5 and Change in Clinical Disease Activity Index (CDAI) | ΔTUVglobal[5w] and response to new anti-TNFα bDMARD therapy defined by the CFB of CDAI to 12 +/- 1 weeks and 24 +/- 1 weeks. | Up to 213 days | 
| Concordance of TUV Baseline to Week 5 and Clinical Disease Activity Index (CDAI),28-joint count Disease Activity Score (DAS28), and American College of Rheumatology (ACR) Response Criteria | Concordance of ΔTUVglobal[5w] (without bucketing) and clinical criteria, including ACR Response Criteria, CDAI, DAS28, and HAQ-DI©. Concordance between ΔTUVglobal[5w] and the clinical criteria will be evaluated using NPV, PPV, sensitivity, specificity, and overall accuracy. | Up to 213 days | 
| Concordance of TUV Baseline to Week 12 and Clinical Disease Activity Index (CDAI),28-joint count Disease Activity Score (DAS28), and American College of Rheumatology (ACR) Response Criteria | Concordance of ΔTUVglobal[12w] and change in clinical criteria, including ACR Response Criteria, CDAI, DAS28, and HAQ-DI©. Concordance between ΔTUVglobal[12w] and the clinical criteria will be evaluated using NPV, PPV, sensitivity, specificity, and overall accuracy. | Up to 213 days | 
| Correlation of TUV Baseline to Week 5 and ACR Response Criteria Components | Correlation of ΔTUVglobal[5w] and response to new anti-TNFα bDMARD therapy from baseline to 24 +/- 1 weeks defined by the changes from baseline in each of the ACR Response Criteria components, including: Tender joint count (TJC) Swollen joint count (SJC) Patient assessment of global disease activity Rheumatologist assessment of global disease activity Patient assessment of pain Patient assessment of physical function Acute-phase reactant value | Up to 213 days | 
| Safety of IV-administered Tilmanocept Radiolabled with Tc 99m Assessed by AEs | Incidence of AEs related to Tc 99m tilmanocept. | Up to 213 days | 
| Safety of IV-administered Tilmanocept Radiolabled with Tc 99m Assessed by Number of Participants with Changes Over Time in Clinical Laboratory Tests | Number of participants with changes over time in clinical laboratory tests (hematology, serum chemistry, urinalysis, and RA panel). | Up to 213 days | 
| Safety of IV-administered Tilmanocept Radiolabled with Tc 99m Assessed by Number of Participants with Changes Over Time in ECG Parameters | Number of participants with changes over time in ECG parameters (PRS Interval, QRS Duration, QT Interval, and QTc Interval). | Up to 213 days | 
| Safety of IV-administered Tilmanocept Radiolabled with Tc 99m Assessed by Number of Participants with Changes Over Time in Vital Signs | Number of participants with changes over time in vital signs (blood pressure, heart rate, respiratory rate, and temperature). | Up to 213 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RA, Tilmanocept