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

Rheumatoid Arthritis Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05246280
• Other study ID #: NAV3-33
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 2, 2022
• Est. completion date: June 2025

Study information

• Verified date: June 2024
• Source: Navidea Biopharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 523
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-TNFa 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].

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• TC99m-tilmanocept
Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.

Locations

Country	Name	City	State
United States	Highlands Advanced Rheumatology and Arthritis Center	Avon Park	Florida
United States	Attune Health Research	Beverly Hills	California
United States	Believe Clinical Trials	Coral Springs	Florida
United States	Arthritis and Osteoporosis Center of Coastal Bend	Corpus Christi	Texas
United States	Nouvelle Clinical Research	Cutler Bay	Florida
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Vida Clinical Research	Kissimmee	Florida
United States	Physician Research Collaboration	Lincoln	Nebraska
United States	Life Clinical Trials	Margate	Florida
United States	D&H National Research Centers, Inc	Miami	Florida
United States	Advanced Clinical Research of Orlando	Ocoee	Florida
United States	University of California, San Francisco	San Francisco	California
United States	Essential Medical Research	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Navidea Biopharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Specificity of Tilmanocept Uptake Value (TUV)	Specificity of the change in TUVglobal with bucketing from baseline to 5 weeks after a change in anti-TNFa therapy (?TUVglobal[5w] with bucketing) with respect to ACR50 at week 24 after the change in therapy.	Up to 213 days
Primary	Sensitivity of Tilmanocept Uptake Value (TUV)	Sensitivity of the change in TUVglobal with bucketing from baseline to 5 weeks after change in anti-TNFa therapy (?TUVglobal[5w] with bucketing) with respect to ACR50 at week 24 after the change in therapy.	Up to 213 days
Secondary	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-TNFa therapy	Up to 213 days
Secondary	Sensitivity and specificity of ?TUVglobal[5w] with bucketing with respect to ACR50 at Week 12	Concordance of ?TUVglobal[5w] with bucketing and ACR50 at week 12, evaluated using sensitivity and specificity.	Up to 213 days
Secondary	NPV, and PPV, and OA of ?TUVglobal[5w] with bucketing with respect to ACR50 at Weeks 12 and 24	Concordance of ?TUVglobal[5w] (with bucketing) and clinical criteria, including ACR Response Criteria, CDAI, DAS28, and HAQ-DI©. Concordance between ?TUVglobal[5w] and the clinical criteria will be evaluated using NPV, PPV and overall accuracy.	up to 213 days
Secondary	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
Secondary	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-TNFa 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
Secondary	Concordance of TUV Baseline to Week 5 and Change in Clinical Disease Activity Index (CDAI)	?TUVglobal[5w] and response to new anti-TNFa bDMARD therapy defined by the CFB of CDAI to 12 +/- 1 weeks and 24 +/- 1 weeks.	Up to 213 days
Secondary	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 ?TUVglobal[5w] (without bucketing) and clinical criteria, including ACR Response Criteria, CDAI, DAS28, and HAQ-DI©. Concordance between ?TUVglobal[5w] and the clinical criteria will be evaluated using NPV, PPV, sensitivity, specificity, and overall accuracy.	Up to 213 days
Secondary	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 ?TUVglobal[12w] and change in clinical criteria, including ACR Response Criteria, CDAI, DAS28, and HAQ-DI©. Concordance between ?TUVglobal[12w] and the clinical criteria will be evaluated using NPV, PPV, sensitivity, specificity, and overall accuracy.	Up to 213 days
Secondary	Correlation of TUV Baseline to Week 5 and ACR Response Criteria Components	Correlation of ?TUVglobal[5w] and response to new anti-TNFa 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
Secondary	Safety of IV-administered Tilmanocept Radiolabled with Tc 99m Assessed by AEs	Incidence of AEs related to Tc 99m tilmanocept.	Up to 213 days
Secondary	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
Secondary	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
Secondary	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