Clinical trial NCT03938636: Evaluation of the Precision and Sensitivity of Tilmanocept Uptake Value (TUV) on Tc 99m Tilmanocept Planar Imaging
Official title: Evaluation of the Precision and Sensitivity of Tilmanocept Uptake Value (TUV) on Tc 99m Tilmanocept Planar Imaging
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: RA
healthy control
tilmanocept
diagnostic
imaging
Lead sponsor: Navidea Biopharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-05-06
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: DIAGNOSTIC

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)?

Detailed 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.

Eligibility criteria: 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-TNFα 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.

Primary outcomes:
measure: Arms 1 & 2: Assess Camera-specific Precision of TUV
timeFrame: Day 0 tilmanocept injection followed by imaging at 60 minutes (60A) and 75 minutes (60B) and at 180 minutes (180A) and 195 minutes (180B).
measure: Arms 1 and 2: Stability of the Mean/Variance Relationship
timeFrame: Day 0 tilmanocept injection followed by imaging at 60 minutes and 180 minutes.
measure: Arm 3: Correlation of ΔTUVglobal[5w] and Response to Therapy
timeFrame: 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.
measure: Longitudinal (8-day) Variation of TUV
timeFrame: Imaging (60 minutes after tilmanocept injection) on Day 0 and Day 8
Secondary outcomes:
measure: Arm 1 Normal Ranges of TUVjoint
timeFrame: Images obtained 60 minutes after tilmanocept injection on Day 0.
measure: 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
timeFrame: A SPECT/CT scan was performed at approximately 210 minutes after the tilmanocept injection on Day 8 of the trial.
measure: Arm 3 (Correlation of TUVglobal[Baseline] and Response to Therapy)
timeFrame: 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.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Imaging Endpoints
state: Arizona
city: Los Angeles
country: United States
facility: Axis Clinical Trials
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Palmetto Bay
country: United States
facility: Innovation Medical Research Center
state: Florida
city: Lincoln
country: United States
facility: Physician Research Collaboration
state: Nebraska
city: Cleveland
country: United States
facility: University Hospitals
state: Ohio
city: Kettering
country: United States
facility: Kettering Medical Center
state: Ohio
city: Tulsa
country: United States
facility: Central States Research
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: Navidea Biopharmaceuticals
name: Michael Blue, MD
role: STUDY_DIRECTOR
References: