Development of a Normative Database for Rheumatoid Arthritis (RA) Imaging With Tc99m Tilmanocept

NCT04947137 | Completed Phase 2 Results FDA Drug

• 1 other identifier: NAV3-35
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 7

Brief Summary

This study will establish a normative database of Tilmanocept Uptake Values (TUVjoint) in healthy controls age-matched to the RA population.

Conditions

Rheumatoid Arthritis

Keywords

RA; Healthy control; Tilmanocept

Outcome Measures

Primary Outcomes (2)

• Normal Limits of TUVjoint in Healthy Subjects

  The normal limits of TUVjoint (on a per joint basis) in HC subjects, which are defined as the 5 and 95 percentiles of TUVjoint of bilateral joints (i.e., bilateral wrists, metacarpophalangeal joint \[MCPs\], proximal interphalangeal \[PIPs\]).

  Up to 39 days

• Qualitative Evaluation of SPECT/CT for Tilmanocept Localization

  Presence/absence of tilmanocept localization in the hands and wrists will be summarized with frequency counts and percentages by reader and joint.

  Up to 39 days

Secondary Outcomes (3)

• Normal Distribution of TUVjoint

  Up to 39 days

• Quantitative Evaluation of SPECT/CT

  Up to 39 days

• Planar and SPECT/CT Comparison

  Up to 39 days

Other Outcomes (1)

• Safety Objective: To Evaluate Safety Through the Examination of AE Incidence and Changes Over Time in Laboratory Tests, Vital Signs, and Physical Examination Findings.

  Up to 39 days

Study Arms (2)

Subjects Free of Inflammatory Disease

EXPERIMENTAL

The first arm will be comprised of HCs who are deemed to be clinically free of inflammatory diseases, arthropathies, and/or arthroplasties and clinically free of joint pain for at least 28 days prior to the consent date.

Drug: Tc99m tilmanocept

Healthy Controls and RA Subjects on Stable Therapy

EXPERIMENTAL

The second arm is comprised of \[1\] disease-free HCs and \[2\] clinically diagnosed RA subjects on stable 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: Lymphoseek

Healthy Controls and RA Subjects on Stable Therapy; Subjects Free of Inflammatory Disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ALL SUBJECTS
• 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 has agreed to not engage in any diet, lifestyle, or medication changes until study completion.
• HEALTHY CONTROL SUBJECTS
• The subject is 30 years of age or greater at the time of consent.
• The subject is deemed to be clinically free of any inflammatory disease(s), autoimmune disease(s), or arthropathies and has not experienced joint pain for at least 28 days prior to the consent date.
• The subject is not currently on anti-inflammatory drugs (including non-steroidal anti-inflammatory drugs \[NSAIDs\]) and has not taken any anti-inflammatories for at least 28 days prior to the consent date.
• For all ongoing concomitant medications, the subject has maintained a stable dose for at least 28 days prior to the consent date.
• CLINICALLY DIAGNOSED ACTIVE RA SUBJECTS
• \. The subject is at least 18 years of age and was ≥ 18 years of age at the time of RA diagnosis.
• \. The subject has moderate to severe 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 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 imaging visit (Day 0). 7. If the subject is receiving bDMARD or janus kinase (JAK) inhibitor therapy, they have been at a stable dose \> 60 days prior to the imaging visit (Day 0). 8. If the subject is receiving NSAIDs or oral corticosteroids, the dose has been stable for ≥ 28 days prior to the 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 therapy or chemotherapy in the past six months.
• 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 or compromise the safety of the subject or the quality of the data.
• The subject has any unstable medical illnesses, including hepatic, renal, gastroenterologic, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
• 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 Tc 99m tilmanocept administration (Day 0).
• The subject has received intra-articular corticosteroid injections ≤ 8 weeks prior to Tc 99m tilmanocept administration (Day 0).
• The subject has received any radiopharmaceutical within 7 days or 10 half-lives prior to Tc 99m tilmanocept administration (Day 0).
• Healthy Controls only: The subject has a positive rheumatoid factor and an elevated ESR or CRP.

Sponsors & Collaborators

• Navidea Biopharmaceuticals: lead

Study Sites (7)

San Marcus Research Clinic

Miami Lakes, Florida, 33014, United States

Location

Innovation Medical Research Center

Palmetto Bay, Florida, 33157, United States

Location

Kettering Medical Center

Kettering, Ohio, 45429, United States

Location

Essential Medical Research

Tulsa, Oklahoma, 74137, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Sun Research Institute

San Antonio, Texas, 78215, United States

Location

Tranquility Research

Webster, Texas, 77598, 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

Analysis of NAV3-35 trial data was halted prior to evaluation of the acquired planar and SPECT/CT images. Preliminary analysis of data from other trials indicated that the ability of Tc 99m tilmanocept imaging to predict response to anti-TNFα therapy in RA patients would not be sufficient for the product to be commercially viable. Therefore, further development of the product for this indication was halted. Note that all subjects had completed the trial.

Results Point of Contact

• Title: Senior Medical Director
• Organization: Navidea Biopharmaceuticals

mblue@navidea.com

6149737555

Study Officials

• Michael Blue, MD

  Navidea Biopharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a prospective, open-label, multicenter, single-dose study designed to develop a normative database of TUVjoint in HCs and to assess the feasibility of qualitative and quantitative SPECT/CT assessments in HCs and subjects with active RA. Subjects will be enrolled in 1 of 2 study arms with distinct study procedures in accordance with Arm-specific eligibility requirements.

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: July 1, 2021
• Study Start: May 27, 2021
• Primary Completion: January 21, 2022
• Study Completion: January 21, 2022
• Last Updated: January 8, 2025
• Results First Posted: January 8, 2025

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)