Clinical trial NCT05246280: Tc 99m Tilmanocept Imaging for Early Prediction of Anti-TNFα Therapy Response in Moderate to Severe Active RA
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: RA
Tilmanocept
Lead sponsor: Navidea Biopharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-02-18
Enrollment: 169
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: 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 \[e.g., +Purified Protein Derivative (PPD) test, Human Immunodeficiency Virus (HIV), Hepatitis B\].

Primary outcomes:
measure: Specificity of Tilmanocept Uptake Value (TUV)
timeFrame: Up to 213 days
measure: Sensitivity of Tilmanocept Uptake Value (TUV)
timeFrame: Up to 213 days
Secondary outcomes:
measure: Negative Predictive Value (NPV) of TUV Baseline at Week 24
timeFrame: Up to 213 days
measure: Sensitivity and Specificity of ΔTUVglobal[5w] With Bucketing With Respect to ACR50 at Week 12
timeFrame: Up to 213 days
measure: NPV, and PPV, and OA of ΔTUVglobal[5w] With Bucketing With Respect to ACR50 at Weeks 12 and 24
timeFrame: up to 213 days
measure: Negative Predictive Value (NPV) of TUV Baseline at Week 12
timeFrame: up to 213 days
measure: 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
timeFrame: Up to 213 days
measure: Concordance of TUV Baseline to Week 5 and Change in Clinical Disease Activity Index (CDAI)
timeFrame: Up to 213 days
measure: 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
timeFrame: Up to 213 days
measure: 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
timeFrame: Up to 213 days
measure: Correlation of TUV Baseline to Week 5 and ACR Response Criteria Components
timeFrame: Up to 213 days
measure: Safety of IV-administered Tilmanocept Radiolabled With Tc 99m Assessed by AEs
timeFrame: Up to 213 days
measure: Safety of IV-administered Tilmanocept Radiolabled With Tc 99m Assessed by Number of Participants With Changes Over Time in Clinical Laboratory Tests
timeFrame: Up to 213 days
measure: Safety of IV-administered Tilmanocept Radiolabled With Tc 99m Assessed by Number of Participants With Changes Over Time in ECG Parameters
timeFrame: Up to 213 days
measure: Safety of IV-administered Tilmanocept Radiolabled With Tc 99m Assessed by Number of Participants With Changes Over Time in Vital Signs
timeFrame: Up to 213 days
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Attune Health Research
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Avon Park
country: United States
facility: Highlands Advanced Rheumatology and Arthritis Center
state: Florida
city: Coral Springs
country: United States
facility: Believe Clinical Trials
state: Florida
city: Cutler Bay
country: United States
facility: Nouvelle Clinical Research
state: Florida
city: Kissimmee
country: United States
facility: Vida Clinical Research
state: Florida
city: Margate
country: United States
facility: Life Clinical Trials
state: Florida
city: Miami
country: United States
facility: D&H National Research Centers, Inc
state: Florida
city: Ocoee
country: United States
facility: Advanced Clinical Research of Orlando
state: Florida
city: Lincoln
country: United States
facility: Physician Research Collaboration
state: Nebraska
city: Tulsa
country: United States
facility: Essential Medical Research
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Corpus Christi
country: United States
facility: Arthritis and Osteoporosis Center of Coastal Bend
state: Texas
Study officials:
affiliation: Navidea Biopharmaceuticals
name: Michael Blue, MD
role: STUDY_DIRECTOR
References: