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

NCT05246280 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: NAV3-33
• Study Type: interventional
• Target: 169
• Locations: 1 country
• Sites: 13

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.

Conditions

Rheumatoid Arthritis

Keywords

RA; Tilmanocept

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (13)

• Negative Predictive Value (NPV) of TUV Baseline at Week 24

  Up to 213 days

• Sensitivity and Specificity of ΔTUVglobal[5w] With Bucketing With Respect to ACR50 at Week 12

  Up to 213 days

• NPV, and PPV, and OA of ΔTUVglobal[5w] With Bucketing With Respect to ACR50 at Weeks 12 and 24

  up to 213 days

• Negative Predictive Value (NPV) of TUV Baseline 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

  Up to 213 days

Study Arms (1)

Candidates for initiation of anti-TNFα bDMARD therapy

EXPERIMENTAL

All subjects will be candidates for initiation of, or change to, a new anti-TNFα bDMARD for RA treatment.

Drug: TC99m-tilmanocept

Interventions

TC99m-tilmanocept DRUG

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

Also known as: tilmanocept, Lymphoseek

Candidates for initiation of anti-TNFα bDMARD therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Navidea Biopharmaceuticals: lead

Study Sites (13)

Attune Health Research

Beverly Hills, California, 90211, United States

Location

University of California, San Francisco

San Francisco, California, 94110, United States

Location

Highlands Advanced Rheumatology and Arthritis Center

Avon Park, Florida, 33825, United States

Location

Believe Clinical Trials

Coral Springs, Florida, 33065, United States

Location

Nouvelle Clinical Research

Cutler Bay, Florida, 33189, United States

Location

Vida Clinical Research

Kissimmee, Florida, 34741, United States

Location

Life Clinical Trials

Margate, Florida, 33063, United States

Location

D&H National Research Centers, Inc

Miami, Florida, 33155, United States

Location

Advanced Clinical Research of Orlando

Ocoee, Florida, 34761, United States

Location

Physician Research Collaboration

Lincoln, Nebraska, 68516, United States

Location

Essential Medical Research

Tulsa, Oklahoma, 74137, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Arthritis and Osteoporosis Center of Coastal Bend

Corpus Christi, Texas, 78415, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

technetium-diethylenetriaminepentaacetic acid-mannosyl-dextran

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

Available data from this trial was being presented as an abbreviated clinical study report to the FDA under the IND as not all efficacy analyses were completed. The trail was halted before completion; therefore tables, listings, and figures were not generated. All available safety data has been presented.

Results Point of Contact

• Title: Michael Blue, MD
• Organization: Navidea Biopharmaceuticals

mblue@navidea.com

6145714313

Study Officials

• Michael Blue, MD

  Navidea Biopharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: February 18, 2022
• Study Start: March 2, 2022
• Primary Completion: July 9, 2024
• Study Completion: July 9, 2024
• Last Updated: January 23, 2025
• Results First Posted: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)