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

Phase 3TerminatedNCT05246280

Navidea Biopharmaceuticals169 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

169

Conditions

Rheumatoid Arthritis

Interventions

TC99m-tilmanoceptDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 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 is at least 18 years of age and was ≥ 18 years of age at the time of RA diagnosis. 3. The subject is a candidate for initiation of, or change to, a new anti-TNFα bDMARD therapy. 4. 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). 5. 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 \[VAS\]). 6. 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). 7. 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). 8. 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: 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 or chemotherapy within the past 5 years. 4. The subject has an active malignancy or a history of malignancy within the past 5 years. 5. The subject has had a finger, hand, and/or wrist amputation or hand or wrist joint arthroplasty. 6. The subject has renal insufficiency as demonstrated by a glomerular filtration rate of \< 60 mL/min. 7. 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. 8. 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. 9. The subject has a history of hypersensitivity reactions to TNF-inhibitors. 10. The subject has a known allergy to or has had an adverse reaction to dextran exposure. 11. The subject has received an investigational product within 30 days prior to the Tc 99m tilmanocept administration at the first imaging visit (Day 0). 12. The subject has received intra-articular corticosteroid injections ≤ 8 weeks prior to the first imaging visit (Day 0). 13. 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). 14. The subject has heart failure \[New York Heart Association (NYHA) Class III-IV\], a demyelinating disorder, or a chronic/latent infection \[e.g., +Purified Protein Derivative (PPD) test, Human Immunodeficiency Virus (HIV), Hepatitis B\].

Locations (13)

Attune Health Research

Beverly Hills, California, United States

University of California, San Francisco

San Francisco, California, United States

Highlands Advanced Rheumatology and Arthritis Center

Avon Park, Florida, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Up to 213 days

Secondary Outcomes

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

Time frame: 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.

Time frame: 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.

Time frame: 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

Data from ClinicalTrials.gov

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