Evaluation of the Precision and Sensitivity of Tilmanocept Uptake Value (TUV) on Tc 99m Tilmanocept Planar Imaging

NCT03938636 | Completed Phase 2 Results FDA Drug

• 1 other identifier: NAV3-31
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 10

Brief Summary

This clinical trial will look at scans of the hands and wrists taken from healthy control subjects (HCs) and from subjects with rheumatoid arthritis (RA). Before each scan, subjects will be given an injection of Tc 99m tilmanocept to help the scan identify inflammation in the hand and wrist joints, which can be a part of the RA disease. Data from the scans will be used to calculate a number referred to as tilmanocept uptake value (or TUV) that is a measure of how much Tc 99m tilmanocept has located in the joints. The questions this trial aims to answer are:

• How consistent are the scan results (TUVs) when the scans are repeated over time?
• What are normal TUVs in healthy people? This will help define abnormally high values in people with RA.
• Are TUVs calculated early after a person starts a new drug to treat RA able to predict whether that person will have a good response to the drug later on (after it has had time to take full effect several weeks later)?

Conditions

Rheumatoid Arthritis

Keywords

RA; healthy control; tilmanocept; diagnostic; imaging

Outcome Measures

Primary Outcomes (4)

• Arms 1 & 2: Assess Camera-specific Precision of TUV

  The camera-specific precision of TUVjoint in subjects with active RA and Healthy Controls (HCs), which is described as the Root Mean Square Difference (RMSD) between the 15-minute planar images (referred to as A and B images at 60 and 180 minutes). The RMSD is calculated as the square root of the mean squared deviation from zero.

  Day 0 tilmanocept injection followed by imaging at 60 minutes (60A) and 75 minutes (60B) and at 180 minutes (180A) and 195 minutes (180B).

• Arms 1 and 2: Stability of the Mean/Variance Relationship

  The stability of the mean/variance relationship, which is assessed by comparing the Coefficient of Variation (CV) of TUVjoint and TUVglobal in subjects with active RA and in healthy control subjects at 60 and 180 minutes.

  Day 0 tilmanocept injection followed by imaging at 60 minutes and 180 minutes.

• Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy

  The Kendall rank correlation of the change in global TUV from baseline to 5 weeks (ΔTUVglobal\[5w\]) and response to new anti-TNFα bDMARD therapy defined by the change from baseline of CDAI to 12 ± 1 weeks and 24 ± 1 weeks (ΔCDAI12w and ΔCDAI24w).• The Kendall rank correlation of ΔTUVglobal\[5w\] and response to new anti-TNFα bDMARD therapy from baseline to 12 ± 1 weeks and 24 ± 1 weeks defined by ACR Response Criteria (ΔACR12w and ΔACR24w)

  Imaging (60 minutes after tilmanocept injection) on Day 0 and at 5 weeks after new therapy initiation; Assessment of CDAI and ACR Response Criteria at 12 and 24 weeks after new therapy initiation.

• Longitudinal (8-day) Variation of TUV

  Longitudinal (8-day) variation of TUV analyzed for each DAS28 joint, defined as the root mean square deviation (RMSD) and 95% confidence interval for the RMSD for each joint at Day 0 vs Day 8

  Imaging (60 minutes after tilmanocept injection) on Day 0 and Day 8

Secondary Outcomes (3)

• Arm 1 Normal Ranges of TUVjoint

  Images obtained 60 minutes after tilmanocept injection on Day 0.

• Qualitative Evaluations of SPECT/CT as an Indication of Bone Involvement Rather Than Localization Within the Synovial Space in the Hands and Wrists of Arm 2 Subjects

  A SPECT/CT scan was performed at approximately 210 minutes after the tilmanocept injection on Day 8 of the trial.

• Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy)

  Images were obtained 60 minutes after tilmanocept injection on Day 0. New anti-TNFα therapy was initiated after completion of Day 0 procedures. CDAI and ACR were assessed on Day 0 and again 12 and 24 weeks after initiation of new anti-TNFα therapy.

Study Arms (3)

Subjects free of inflammatory disease

EXPERIMENTAL

Arm 1 includes inflammatory-disease-free HCs. Arm 1 was designed to evaluate image/re-image consistency (repeatability and stability) of joint-specific and global TUVs across a variety of image acquisition intervals and to collect normative HC data.

Drug: Tc 99m tilmanocept

RA subjects on stable therapy

EXPERIMENTAL

Arm 2 includes clinically-diagnosed RA subjects on stable treatment. Arm 2 was designed to evaluate image/re-image and test re-test (i.e., repeated dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals.

Drug: Tc 99m tilmanocept

RA subjects who are candidates for initiation of a new anti-TNFα therapy

EXPERIMENTAL

Arm 3 includes clinically-diagnosed RA subjects on stable treatment who are candidates for initiation of, or change to, new anti-TNFα therapy. Arm 3 was designed to assess the efficacy of global TUVs, obtained before and after initiation of a new anti-TNFα therapy, to predict future clinical responsiveness to the new therapy.

Drug: Tc 99m tilmanocept

Interventions

Tc 99m 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

RA subjects on stable therapy; RA subjects who are candidates for initiation of a new anti-TNFα 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.
• ARMS 1 and 2 (only): The subject has agreed to not engage in any diet, lifestyle, or medication changes until study completion.
• HEALTHY CONTROL SUBJECTS
• The subject is between 18 and 80 years of age at the time of consent.
• The subject is deemed to be clinically free of any inflammatory disease(s) 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 NSAIDs) and has not taken 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 first imaging visit (Day 0).
• \. If the subject is receiving bDMARD or janus kinase (JAK) inhibitor therapy, they have been at a stable dose \> 180 days prior to the first imaging visit (Day 0).
• \. If the subject is receiving NSAIDs or oral corticosteroids, the dose has been stable for \> 28 days prior to first imaging visit (Day 1). 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 has had or is currently receiving radiation therapy or chemotherapy.
• 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 3 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 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.
• 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.

Sponsors & Collaborators

• Navidea Biopharmaceuticals: lead

Study Sites (10)

Imaging Endpoints

Scottsdale, Arizona, 85258, United States

Location

Axis Clinical Trials

Los Angeles, California, 90036, United States

Location

University of California San Francisco

San Francisco, California, 94110, United States

Location

Innovation Medical Research Center

Palmetto Bay, Florida, 33157, United States

Location

Physician Research Collaboration

Lincoln, Nebraska, 68516, United States

Location

University Hospitals

Cleveland, Ohio, 44106, United States

Location

Kettering Medical Center

Kettering, Ohio, 45429, United States

Location

Central States Research

Tulsa, Oklahoma, 74136, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Disease

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Navidea Biopharmaceuticals

mrosol@navidea.com

614-822-2320

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 and repeated-dose study designed to evaluate the reliability and sensitivity of TUV assessments in healthy controls and subjects with active RA.

Study Record Dates

• First Submitted: April 24, 2019
• First Posted: May 6, 2019
• Study Start: April 8, 2019
• Primary Completion: February 8, 2021
• Study Completion: June 30, 2021
• Last Updated: August 24, 2023
• Results First Posted: August 24, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)