Clinical trial NCT04078191: Comparison of Tc 99m Tilmanocept Imaging With IHC Analysis of CD206 Expression in Synovial Tissue of Subjects With RA
Official title: A Comparison of Tc 99m Tilmanocept Quantitative Imaging With Immunohistochemical (IHC) Analysis of CD206 Expression in Synovial Tissue From Subjects Clinically Diagnosed With Rheumatoid Arthritis (RA)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: tilmanocept
RA imaging
synovial biopsy
Lead sponsor: Navidea Biopharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-09-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: This study is a comparison of quantitative Tc 99m tilmanocept imaging with IHC analysis of CD206 expression in synovial tissue of RA subjects.

Detailed description: This is a Manocept Platform phase 2b, open-label, multi-center, multinational, non-randomized, single-dose study designed to assess the relationship between quantitative Tc 99m tilmanocept planar imaging and synovial histopathology in subjects clinically diagnosed with RA.

Eligibility criteria: Inclusion Criteria:

1. The subject has provided written informed consent with HIPAA (Health Information Portability and Accountability Act) or equivalent authorization before the initiation of any study-related procedures.
2. Women and men of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) for the duration of the study.
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 RA as determined by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria (score of ≥ 6/10 at or before screening).
5. The subject has a 28-joint disease activity score (DAS28) of ≥ 3.2 (includes the C-reactive protein \[CRP\] 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 biologic disease-modifying antirheumatic drug (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 (nonsteroidal anti-inflammatory drug) or oral corticosteroids, the dose has been at a stable dose for ≥ 28 days prior to imaging. The corticosteroid dose should be ≤ 10 mg/day of prednisone or an equivalent steroid dose.
9. The subject has a hand or wrist joint with a minimum ultrasound gray-scale synovitis score of 2 (range 0 to 3).

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 (Day 0).
9. The subject has received intra-articular corticosteroids ≤ 8 weeks prior to imaging (Day 0).
10. The subject has received any radiopharmaceutical within 7 days or 10 half-lives prior to the administration of Tc 99m tilmanocept (Day 0).
11. The subject has an intolerance to anesthetic and antiseptic agents indicated for the synovial biopsy procedure.
12. The subject is currently receiving anticoagulants (oral anti-platelet agents are permitted) or has a condition that is contraindicated with ultrasound-guided synovial biopsy e.g., needle phobia.

Primary outcomes:
measure: Correlation Between Joint-specific Tilmanocept Uptake and CD206 Expression
timeFrame: Through study completion, up to 45 days
Secondary outcomes:
measure: Correlation Between Joint-specific Tilmanocept Uptake and CD68 and CD163 Expression
timeFrame: Through study completion, up to 45 days
measure: Classification of Synovial Anatomic Pathotype by IHC Assessment
timeFrame: Through study completion, up to 45 days
Other outcomes:
measure: Exploratory Objective: Correlation Between CD206, CD68, and CD163 Expression
timeFrame: Through study completion, up to 45 days
measure: Safety Evaluation - AEs
timeFrame: Through study completion, up to 45 days
measure: Safety Evaluation - Laboratory Tests, ECGs, and Vital Signs
timeFrame: Through study completion, up to 45 days
Locations:
city: Beverly Hills
country: United States
facility: Attune Health
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: London
country: United Kingdom
facility: Barts Hospital
state: England
city: London
country: United Kingdom
facility: Royal Free Hospital
state: England
Study officials:
affiliation: Navidea Biopharmaceuticals
name: Michael Blue, MD
role: STUDY_DIRECTOR
References: