Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03938636
Other study ID # NAV3-31
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date April 8, 2019
Est. completion date June 30, 2021

Study information

Verified date August 2023
Source Navidea Biopharmaceuticals
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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)?


Description:

This trial is a prospective, open-label, multicenter, single and repeated-dose study designed to evaluate the reliability and sensitivity of TUV assessments in healthy control subjects and subjects with active RA. This study is stratified into 3 arms. The first 2 arms, consisting of [1] disease-free HCs and [2] clinically diagnosed RA subjects on stable treatment, respectively, are designed to evaluate the image re-image and/or test re-test (i.e., repeated dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals. The third arm consists of clinically-diagnosed subjects with active RA who are candidates for initiation of, or change to, a new anti-TNFα bDMARD therapy. This arm is designed to assess the efficacy of TUVglobal as an early predictor of response to the new anti-TNFα bDMARD therapy.


Recruitment information / eligibility

Status Completed
Enrollment 116
Est. completion date June 30, 2021
Est. primary completion date February 8, 2021
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: ALL SUBJECTS: 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. 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 3. The subject is between 18 and 80 years of age at the time of consent. 4. 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. 5. 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. 6. 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: 3. The subject is at least 18 years of age and was = 18 years of age at the time of RA diagnosis. 4. 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). 5. 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]). 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. 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). 8. 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. 9. ARM 3 (only): The subject is receiving anti-rheumatic treatment and is a candidate for initiation of, or change to, a new anti-TNFa bDMARD treatment. 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 has had or is currently receiving radiation therapy or chemotherapy. 4. The subject has renal insufficiency as demonstrated by a glomerular filtration rate of < 60 mL/min. 5. 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. 6. 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. 7. The subject has a known allergy to or has had an adverse reaction to dextran exposure. 8. The subject has received an investigational product within 30 days prior to the Tc 99m tilmanocept administration. 9. The subject has received intra-articular corticosteroid injections = 8 weeks prior to the first imaging visit (Day 0). 10. The subject has received any radiopharmaceutical within 7 days or 10 half-lives prior to the administration of Tc 99m tilmanocept.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Tc 99m 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 University Hospitals Cleveland Ohio
United States Altoona Center for Clinical Research Duncansville Pennsylvania
United States Kettering Medical Center Kettering Ohio
United States Physician Research Collaboration Lincoln Nebraska
United States Axis Clinical Trials Los Angeles California
United States Innovation Medical Research Center Palmetto Bay Florida
United States University of Pittsburgh Medical Center Pittsburgh Pennsylvania
United States University of California San Francisco San Francisco California
United States Imaging Endpoints Scottsdale Arizona
United States Central States 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 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).
Primary 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.
Primary Arm 3: Correlation of ?TUVglobal[5w] and Response to Therapy The Kendall rank correlation of the change in global TUV from baseline to 5 weeks (?TUVglobal[5w]) and response to new anti-TNFa bDMARD therapy defined by the change from baseline of CDAI to 12 ± 1 weeks and 24 ± 1 weeks (?CDAI12w and ?CDAI24w).• The Kendall rank correlation of ?TUVglobal[5w] and response to new anti-TNFa bDMARD therapy from baseline to 12 ± 1 weeks and 24 ± 1 weeks defined by ACR Response Criteria (?ACR12w and ?ACR24w) 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.
Primary 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 Arm 1 Normal Ranges of TUVjoint The normal range of tilmanocept uptake values (TUVs) in hand and wrist joints of healthy control subjects, expressed as the mean and standard deviation. TUV is defined as the average pixel intensity of the region of interest (hand or wrist joint) divided by the average pixel intensity of the reference region (includes the region from one wrist region of interest diameter above the wrist region of interest down to the fingertips) Images obtained 60 minutes after tilmanocept injection on Day 0.
Secondary 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 Percent of Arm 2 subjects who had SPECT/CT scans who were determined to have bone involvement rather than localization within the synovial space of the hands and wrists A SPECT/CT scan was performed at approximately 210 minutes after the tilmanocept injection on Day 8 of the trial.
Secondary Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy) The correlation of the TUVglobal[baseline] 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 (?CDAI12w and ?CDAI24w, respectively) and by ACR Response Criteria (ACR12w and ACR24w, respectively). Images were obtained 60 minutes after tilmanocept injection on Day 0. New anti-TNFa 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-TNFa therapy.
See also
  Status Clinical Trial Phase
Completed NCT04226131 - MusculRA: The Effects of Rheumatoid Arthritis on Skeletal Muscle Biomechanics N/A
Completed NCT04171414 - A Study to Evaluate Usability of Subcutaneous Auto-injector of CT-P17 in Patients With Active Rheumatoid Arthritis Phase 3
Completed NCT02833350 - Safety and Efficacy Study of GDC-0853 Compared With Placebo and Adalimumab in Participants With Rheumatoid Arthritis (RA) Phase 2
Completed NCT04255134 - Biologics for Rheumatoid Arthritis Pain (BIORA-PAIN) Phase 4
Recruiting NCT05615246 - Exactech Humeral Reconstruction Prosthesis of Shoulder Arthroplasty PMCF (HRP)
Completed NCT03248518 - Lessening the Impact of Fatigue in Inflammatory Rheumatic Diseases N/A
Completed NCT03514355 - MBSR in Rheumatoid Arthritis Patients With Controlled Disease But Persistent Depressive Symptoms N/A
Recruiting NCT06005220 - SBD121, a Synbiotic Medical Food for RA Management N/A
Recruiting NCT05451615 - Efficacy and Safety of Abatacept Combined With JAK Inhibitor for Refractory Rheumatoid Arthritis Phase 3
Completed NCT05054920 - Eccentric Versus Concentric Exercises for Rotator Cuff Tendinopathy in Patients With Rheumatoid Arthritis N/A
Completed NCT02037737 - Impact and Use of Abatacept IV for Rheumatoid Arthritis in Real Life Setting N/A
Recruiting NCT04079374 - Comparative Efficacy, Safety and Immunogenicity Study of Etanercept and Enbrel Phase 3
Completed NCT02504268 - Effects of Abatacept in Patients With Early Rheumatoid Arthritis Phase 3
Recruiting NCT05496855 - Remote Care in People With Rheumatoid Arthritis N/A
Completed NCT05051943 - A Study of the Real-world Use of an Adalimumab Biosimilar and Evaluation of Nutritional Status on the Therapeutic Response
Recruiting NCT06031415 - Study of GS-0272 in Participants With Rheumatoid Arthritis Phase 1
Recruiting NCT06103773 - A Study of Single and Multiple Oral Doses of TollB-001 Phase 1
Completed NCT05999266 - The Cartilage and Muscle Thickness on Knee Pain in Patients With Rheumatoid Arthritis
Recruiting NCT05302934 - Evaluation of the PHENO4U Data Platform in Patients Undergoing Total Knee Arthroplasty
Recruiting NCT04169100 - Novel Form of Acquired Long QT Syndrome Phase 4