Arthritis, RheumatoidPhase 1/2NCT02865434

Evaluating Safety of Escalating Doses of Tilmanocept by IV Injection and SPECT Imaging in Subjects With and Without RA

A Phase 1/2 study testing Tc99m-tilmanocept, SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection) in people with Arthritis, Rheumatoid, run by Navidea Biopharmaceuticals at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Prospective, open-label, multicenter, dose escalation, safety with pharmacokinetics (PK) and dosimetry study of injected Tc 99m tilmanocept in the detection of and assessment of localization to skeletal joints in subjects with and without active RA by SPECT imaging. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Arthritis, Rheumatoid
What is being tested?: Tc99m-tilmanocept, SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection)
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 39 participants
Where: 1 siteUnited States
Study dates: Jan 2017to Jun 2018
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.
Has a negative urine drug screening for illicit or unprescribed drugs suggestive of drug abuse.
All subjects shall be ≥18 years of age at the time of consent.
CONTROL SUBJECTS:
The subject is deemed to be clinically free of any inflammatory disease (s) and has not experienced joint pain for at least 4 weeks prior to the consent date.

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ACTIVE RHEUMATOID ARTHRITIS SUBJECTS:
The subject has moderate to severe RA as determined by the 2010 ACR/EULAR (score of ≥ 6/10).
The subject has a DAS28 of ≥ 3.2 (includes the Erythrocyte Sedimentation Rate [ESR] test and Visual Analog Scale [VAS]) .
If the subject is receiving methotrexate, they have been at a stable dose for > 4 weeks prior to the Baseline Visit 2 (Day 1).
If the subject is receiving biologic therapy, they have been at a stable dose > 8 weeks prior to the Baseline Visit 2 (Day 1).
If the subject is receiving NSAIDS or oral corticosteroids, the dose has been at a stable dose for > 4 weeks prior to the Baseline Visit 2 (Day 1). The corticosteroid dose should be ≤ 10mg/day of prednisone or an equivalent steroid dose.

Who cannot join

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 for a condition other than rheumatoid arthritis.
The subject has renal insufficiency as demonstrated by serum creatinine clearance of < 60 mL/min.
The subject has hepatic insufficiency as demonstrated by ALT or AST greater than two times the upper limit of normal.
The subject has a chronic or persistent infection or has any condition that would, in the opinion of the examining physician, preclude their participation.

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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 any radiopharmaceutical within 7 days prior to the administration of Tc 99m tilmanocept.

Trial locations and contacts

1 site in 1 country.

United States1 site

Kettering Medical Center
Kettering, Ohio, 45429

Other trials in United States

About this study

Official title: An Evaluation of the Safety of Escalating Doses of Tc 99m Tilmanocept by Intravenous (IV) Injection and Skeletal Joint Imaging With SPECT in Subjects With Active Rheumatoid Arthritis (RA) and Healthy Controls

Read the detailed description

A Manocept Platform prospective, open-label, multicenter, dose escalation, safety with PK and dosimetry study of injected Tc 99m tilmanocept in the detection of and assessment of localization to skeletal joints in subjects with and without active RA by SPECT imaging. All subjects will receive IV administration at one of 3 mass doses: 50 µg, 200 µg, or 400 µg. Within each mass dose group, subjects will receive Tc 99m tilmanocept labeled with one of 3 radiolabel doses: 1 mCi, 5 mCi, or 10 mCi.

All subjects will have a whole body planar SPECT scan. Subjects enrolled in Groups 1-9 will receive a whole body and planar hands scan followed by SPECT/CT scans on areas of interest post injection at 60 minutes ± 15 minutes and 180 minutes ± 15 minutes. Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed at 4 specified time points post injection: 15 ± 5 minutes, 60 ± 15 minutes, 180 ± 15 minutes and 18-20 hours. Planar hand scans will be collected at 60 ± 15 minutes and 180 ± 15 minutes post-injection. PK blood sampling will be performed before injection (within 15 minutes), immediately following injection (within 5 minutes) and at each scanning timepoint. Dosimetry tests will be performed at each scanning timepoint. PK of urine will be assessed through counts of the bladder wall obtained from cumulative quantitative planar imaging from radiation dosimetry.

Conditions: Arthritis, Rheumatoid
Being tested: Tc99m-tilmanocept, SPECT Imaging (60 Minutes post-injection), SPECT Imaging (180 Minutes post-injection), Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 Minutes post-injection)
Medical subject headings: Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Tc99m-tilmanoceptDrug
Also called tilmanocept
Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
SPECT Imaging (60 Minutes post-injection)Procedure or surgery
Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection.
SPECT Imaging (180 Minutes post-injection)Procedure or surgery
Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection.
Whole body planar SPECT imaging (15 Minutes post-injection)Procedure or surgery
Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 15 minutes post-injection for dosimetry.
Whole body planar SPECT imaging (60 Minutes post-injection)Procedure or surgery
Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 60 minutes post-injection for dosimetry.
Whole body planar SPECT imaging (180 Minutes post-injection)Procedure or surgery
Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 180 minutes post-injection for dosimetry.
Whole body planar SPECT imaging (18-20 Hours post-injection)Procedure or surgery
Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 18-20 Hours post-injection for dosimetry.
Blood Collection for PK Testing (15 Mins Before Injection)Procedure or surgery
Blood will be collected for subjects enrolled in Groups 10-11 for the purpose of PK analysis within 15 minutes prior to administration of Tc 99m tilmanocept
Blood Collection for PK Testing (after injection)Procedure or surgery
Blood will be collected for subjects enrolled in Groups 10-11 for the purpose of PK analysis immediately following administration of Tc 99m tilmanocept (00:00)
Blood Collection for PK Testing (15 minutes post injection)Procedure or surgery
Blood will be collected for subjects enrolled in Groups 10-11 for the purpose of PK analysis at 15 ± 5 minutes post injection of Tc 99m tilmanocept
Blood Collection for PK Testing (60 minutes post injection)Procedure or surgery
Blood will be collected for subjects enrolled in Groups 10-11 for the purpose of PK analysis at 60 ± 15 minutes post injection of Tc 99m tilmanocept
Blood Collection for PK Testing (180 minutes post injection)Procedure or surgery
Blood will be collected for subjects enrolled in Groups 10-11 for the purpose of PK analysis at 180 ± 15 minutes post injection of Tc 99m tilmanocept
Blood Collection for PK Testing (18-20 hours post injection)Procedure or surgery
Blood will be collected for subjects enrolled in Groups 10-11 for the purpose of PK analysis at 18-20 hours post injection of Tc 99m tilmanocept
Planar Image with both Hands in Field of ViewProcedure or surgery
Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.

Study groups in NCT02865434
Study group	Role	What they receive
Group 1 (RA)	Experimental	Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Receives: Drug: Tc99m-tilmanocept; Procedure: SPECT Imaging (60 Minutes post-injection); Procedure: SPECT Imaging (180 Minutes post-injection); Procedure: Planar Image with both Hands in Field of View
Group 2 (RA)	Experimental	Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Receives: Drug: Tc99m-tilmanocept; Procedure: SPECT Imaging (60 Minutes post-injection); Procedure: SPECT Imaging (180 Minutes post-injection); Procedure: Planar Image with both Hands in Field of View
Group 3 (RA)	Experimental	Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Receives: Drug: Tc99m-tilmanocept; Procedure: SPECT Imaging (60 Minutes post-injection); Procedure: SPECT Imaging (180 Minutes post-injection); Procedure: Planar Image with both Hands in Field of View
Group 4 (RA)	Experimental	Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Receives: Drug: Tc99m-tilmanocept; Procedure: SPECT Imaging (60 Minutes post-injection); Procedure: SPECT Imaging (180 Minutes post-injection); Procedure: Planar Image with both Hands in Field of View
Group 5 (RA)	Experimental	Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Receives: Drug: Tc99m-tilmanocept; Procedure: SPECT Imaging (60 Minutes post-injection); Procedure: SPECT Imaging (180 Minutes post-injection); Procedure: Planar Image with both Hands in Field of View
Group 6 (RA)	Experimental	Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Receives: Drug: Tc99m-tilmanocept; Procedure: SPECT Imaging (60 Minutes post-injection); Procedure: SPECT Imaging (180 Minutes post-injection); Procedure: Planar Image with both Hands in Field of View
Group 7 (RA)	Experimental	Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Receives: Drug: Tc99m-tilmanocept; Procedure: SPECT Imaging (60 Minutes post-injection); Procedure: SPECT Imaging (180 Minutes post-injection); Procedure: Planar Image with both Hands in Field of View
Group 8 (RA)	Experimental	Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Receives: Drug: Tc99m-tilmanocept; Procedure: SPECT Imaging (60 Minutes post-injection); Procedure: SPECT Imaging (180 Minutes post-injection); Procedure: Planar Image with both Hands in Field of View
Group 9 (RA)	Experimental	Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Receives: Drug: Tc99m-tilmanocept; Procedure: SPECT Imaging (60 Minutes post-injection); Procedure: SPECT Imaging (180 Minutes post-injection); Procedure: Planar Image with both Hands in Field of View
Group 10 (Healthy Controls)	Experimental	Group 10 will receive Tc99m-tilmanocept at the MTD via IV injection, Whole body planar SPECT imaging (15 Minutes post-injection) , Whole body planar SPECT imaging (60 minutes post-injection) , Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection), Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection), Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection) , Blood Collection for PK Testing (15 minutes post injection) , Blood Collection for PK Testing (60 minutes post injection) , Blood Collection for PK Testing (180 minutes post injection) , and Blood Collection for PK Testing (18-20 hours post injection). Receives: Procedure: Whole body planar SPECT imaging (15 Minutes post-injection); Procedure: Whole body planar SPECT imaging (60 Minutes post-injection); Procedure: Whole body planar SPECT imaging (180 Minutes post-injection); Procedure: Whole body planar SPECT imaging (18-20 Hours post-injection); Procedure: Blood Collection for PK Testing (15 Mins Before Injection); Procedure: Blood Collection for PK Testing (after injection); Procedure: Blood Collection for PK Testing (15 minutes post injection); Procedure: Blood Collection for PK Testing (60 minutes post injection); Procedure: Blood Collection for PK Testing (180 minutes post injection); Procedure: Blood Collection for PK Testing (18-20 hours post injection); Procedure: Planar Image with both Hands in Field of View
Group 11 (RA)	Experimental	Group 11 will receive Tc99m-tilmanocept at the MTD via IV injection, Whole body planar SPECT imaging (15 Minutes post-injection) , Whole body planar SPECT imaging (60 minutes post-injection) , Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection), Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection), Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection) , Blood Collection for PK Testing (15 minutes post injection) , Blood Collection for PK Testing (60 minutes post injection) , Blood Collection for PK Testing (180 minutes post injection) , and Blood Collection for PK Testing (18-20 hours post injection). Receives: Procedure: Whole body planar SPECT imaging (15 Minutes post-injection); Procedure: Whole body planar SPECT imaging (60 Minutes post-injection); Procedure: Whole body planar SPECT imaging (180 Minutes post-injection); Procedure: Whole body planar SPECT imaging (18-20 Hours post-injection); Procedure: Blood Collection for PK Testing (15 Mins Before Injection); Procedure: Blood Collection for PK Testing (after injection); Procedure: Blood Collection for PK Testing (15 minutes post injection); Procedure: Blood Collection for PK Testing (60 minutes post injection); Procedure: Blood Collection for PK Testing (180 minutes post injection); Procedure: Blood Collection for PK Testing (18-20 hours post injection); Procedure: Planar Image with both Hands in Field of View

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of Adverse Drug Reaction
Number of participants that experienced pharmacologic activity or ADR in each dose group.
Measured: From Enrollment to termination, up to 53 days

Secondary outcomes (12)

Per Subject Localization Rate of Tc 99m Tilmanocept by SPECT Imaging
Tc 99m Tilmanocept localization is defined as the visually (i.e., qualitatively) determined binary categorization of Tc 99m tilmanocept activity in a given DAS28 joint. The purpose of the visual assessments is to obtain dichotomized classifications of tracer uptake (herein referenced as 'localization') on planar images. Per subject localization rate is the number of subjects with at least one localized DAS28 joint per number of subjects in the analysis population.
Measured: For Groups 1-9, 60 ± 15 min or 180 ± 15 minute post injection planar and SPECT/CT images are used
Tc 99m Tilmanocept Joint Localization Rate in Rheumatoid Arthritis Identified Joints
Per joint (clinically RA-identified) joint localization rate of Tc 99m tilmanocept is defined as the number of localized joints per number of joints from subjects in the analysis population Groups 1-9 using SPECT imaging.
Measured: Whole-body planar scan at 60 ± 15 and 180 ± 15 minutes post Tc 99m tilmanocept administration with a duration of approximately 25 to 30 minutes at each timepoint.
Concordance
Concordance is defined as the relationship or the presence of Tc99m localization in anatomical areas of active RA defined by clinical symptomology (defined as joint swelling (SJC) and/or tenderness (TJC) during the screening DAS28 evaluation).
Measured: Qualitative (i.e., visual) assessments of planar images were acquired at the 60 ± 15-minute and 180 ± 15-minute timepoints in Groups 1-9.
Localization Intensity
Localization intensity is defined as the presence of Tc99m in each DAS28 joint and is output in tilmanocept uptake value (TUV) units, as computed using the following equation:
〖TUV〗=ROI/BRAIN×100 where ROI = decay-corrected avg voxel intensity of the joint ROI and BRAIN =decay-corrected avg voxel intensity of the brain RR
Measured: Post-injection imaging at 60±15 and 180±15 min
Per Subject Localization Rate of Tc 99m Tilmanocept in Areas Other Than RA
Per subject localization rate of Tc 99m tilmanocept in areas other than RA is defined as the number of subjects with at least one localized DAS28 joint per number of subjects in the analysis population.
Measured: Imaging taken 60 ± 15 min and 180 ± 15 min post-injection
Maximum Observed Concentration (Cmax)
Maximum observed concentration (Cmax) will be calculated, whenever possible, using Tc 99m tilmanocept total radioactivity in whole blood and urine.
Measured: 15 minutes prior to administration. Immediately after administration. 15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post administration
Time to Cmax (Tmax)
Time to Cmax (tmax) will be calculated, whenever possible, using Tc 99m tilmanocept total radioactivity in whole blood and urine.
Measured: Radioactivity was quantitated at each time point -15 mins prior to administration• Immediately after administration •15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post admi
Area Under the Concentration-time Curve (AUC) From Hour 0 to the Last Measureable Concentration (AUC0-t)
Area under the concentration-time curve (AUC) from Hour 0 to the last measureable concentration (18 to 20 hours) (AUC0-t) will be calculated, whenever possible, using Tc 99m tilmanocept total radioactivity in whole blood and urine.
Measured: Hour 0 to hour 18-20, with time points immediately post injection, 0.25 hr, 1 hr, 3 hr and 18-20 hr after injection
AUC Extrapolated to Infinity
AUC extrapolated to infinity will be calculated, whenever possible, using Tc 99m tilmanocept total radioactivity in whole blood and urine.
Measured: 15 mins prior to administration • Immediately after administration • 15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post administration
Apparent Terminal Elimination Rate Constant (Z)
Apparent terminal elimination rate constant (Z) will be calculated, whenever possible, using Tc 99m tilmanocept total radioactivity in whole blood and urine.
Measured: 15 mins prior to administration • Immediately after administration • 15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post administration
Apparent Terminal Elimination Half-life (t1/2)
Apparent terminal elimination half-life (t1/2) will be calculated, whenever possible, using Tc 99m tilmanocept total radioactivity in whole blood and urine.
Measured: 15 mins prior to administration • Immediately after administration • 15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post administration
Radiation Dosimetry of Tc 99m Tilmanocept
Mean total radiation dose per organ (mSv/MBq) in HC females, HC males, females with active RA, and males with active RA.
Results were obtained at the subject level from Hybrid Dosimetry™ Version 2.8.3 and OLINDA/EXM® Version 2.1RC93 in accordance with NAV3-21 Protocol Amendment 6. The Hybrid Dosimetry™ function provides an efficient way to generate kinetic data for selected organs via regions of interest (ROI) drawing. From this data, residence times are calculated and transferred to OLINDA/EXM®, which generates absorbed dose tables using the MIRD methodology.
Measured: Planar images were taken 15 ± 5 minutes, 60 ± 5 minutes, 180 ± 5 minutes, 18 to 20 hours after Tc 99m tilmanocept administration and processed in accordance with the NAV3-21 protocol endpoints using established dosimetry software.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2017Jun 2018

First posted12 Aug 2016 (estimated)
Study startJan 2017
Primary completionJun 2018
Study completionJun 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Arthritis, RheumatoidStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Diagnosis
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 39 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02865434
Sponsor's protocol ID: NAV3-21
Status last verified: Aug 2021
First submitted: 5 Aug 2016
Last updated: 12 Aug 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 12 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Evaluation of the Safety of Escalating Doses of Tc 99m Tilmanocept by Intravenous (IV) Injection and Skeletal Joint Imaging With SPECT in Subjects With Active Rheumatoid Arthritis (RA) and Healthy Controls
ClinicalTrials.gov ID: NCT02865434
Acronym / sponsor ID: NAV3-21
Conditions: Arthritis, Rheumatoid
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 39 participants (actual)
Lead sponsor: Navidea BiopharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Jan 2017 (actual)
Primary completion: Jun 2018 (actual)
Study completion: Jun 2018 (actual)
First posted: 12 Aug 2016 (estimated)
Results: Posted 12 Aug 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Diagnosis
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 11

Arm	Type	Receives
Group 1 (RA)	Experimental	Drug: Tc99m-tilmanocept, Procedure: SPECT Imaging (60 Minutes post-injection), Procedure: SPECT Imaging (180 Minutes post-injection), Procedure: Planar Image with both Hands in Field of ViewGroup 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection).
Group 2 (RA)	Experimental	Drug: Tc99m-tilmanocept, Procedure: SPECT Imaging (60 Minutes post-injection), Procedure: SPECT Imaging (180 Minutes post-injection), Procedure: Planar Image with both Hands in Field of ViewGroup 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection).
Group 3 (RA)	Experimental	Drug: Tc99m-tilmanocept, Procedure: SPECT Imaging (60 Minutes post-injection), Procedure: SPECT Imaging (180 Minutes post-injection), Procedure: Planar Image with both Hands in Field of ViewGroup 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection).
Group 4 (RA)	Experimental	Drug: Tc99m-tilmanocept, Procedure: SPECT Imaging (60 Minutes post-injection), Procedure: SPECT Imaging (180 Minutes post-injection), Procedure: Planar Image with both Hands in Field of ViewGroup 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection).
Group 5 (RA)	Experimental	Drug: Tc99m-tilmanocept, Procedure: SPECT Imaging (60 Minutes post-injection), Procedure: SPECT Imaging (180 Minutes post-injection), Procedure: Planar Image with both Hands in Field of ViewGroup 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection).
Group 6 (RA)	Experimental	Drug: Tc99m-tilmanocept, Procedure: SPECT Imaging (60 Minutes post-injection), Procedure: SPECT Imaging (180 Minutes post-injection), Procedure: Planar Image with both Hands in Field of ViewGroup 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection).
Group 7 (RA)	Experimental	Drug: Tc99m-tilmanocept, Procedure: SPECT Imaging (60 Minutes post-injection), Procedure: SPECT Imaging (180 Minutes post-injection), Procedure: Planar Image with both Hands in Field of ViewGroup 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection).
Group 8 (RA)	Experimental	Drug: Tc99m-tilmanocept, Procedure: SPECT Imaging (60 Minutes post-injection), Procedure: SPECT Imaging (180 Minutes post-injection), Procedure: Planar Image with both Hands in Field of ViewGroup 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection).
Group 9 (RA)	Experimental	Drug: Tc99m-tilmanocept, Procedure: SPECT Imaging (60 Minutes post-injection), Procedure: SPECT Imaging (180 Minutes post-injection), Procedure: Planar Image with both Hands in Field of ViewGroup 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection).
Group 10 (Healthy Controls)	Experimental	Procedure: Whole body planar SPECT imaging (15 Minutes post-injection), Procedure: Whole body planar SPECT imaging (60 Minutes post-injection), Procedure: Whole body planar SPECT imaging (180 Minutes post-injection), Procedure: Whole body planar SPECT imaging (18-20 Hours post-injection), Procedure: Blood Collection for PK Testing (15 Mins Before Injection), Procedure: Blood Collection for PK Testing (after injection), Procedure: Blood Collection for PK Testing (15 minutes post injection), Procedure: Blood Collection for PK Testing (60 minutes post injection), Procedure: Blood Collection for PK Testing (180 minutes post injection), Procedure: Blood Collection for PK Testing (18-20 hours post injection), Procedure: Planar Image with both Hands in Field of ViewGroup 10 will receive Tc99m-tilmanocept at the MTD via IV injection, Whole body planar SPECT imaging (15 Minutes post-injection) , Whole body planar SPECT imaging (60 minutes post-injection) , Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection), Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection), Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection) , Blood Collection for PK Testing (15 minutes post injection) , Blood Collection for PK Testing (60 minutes post injection) , Blood Collection for PK Testing (180 minutes post injection) , and Blood Collection for PK Testing (18-20 hours post injection).
Group 11 (RA)	Experimental	Procedure: Whole body planar SPECT imaging (15 Minutes post-injection), Procedure: Whole body planar SPECT imaging (60 Minutes post-injection), Procedure: Whole body planar SPECT imaging (180 Minutes post-injection), Procedure: Whole body planar SPECT imaging (18-20 Hours post-injection), Procedure: Blood Collection for PK Testing (15 Mins Before Injection), Procedure: Blood Collection for PK Testing (after injection), Procedure: Blood Collection for PK Testing (15 minutes post injection), Procedure: Blood Collection for PK Testing (60 minutes post injection), Procedure: Blood Collection for PK Testing (180 minutes post injection), Procedure: Blood Collection for PK Testing (18-20 hours post injection), Procedure: Planar Image with both Hands in Field of ViewGroup 11 will receive Tc99m-tilmanocept at the MTD via IV injection, Whole body planar SPECT imaging (15 Minutes post-injection) , Whole body planar SPECT imaging (60 minutes post-injection) , Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection), Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection), Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection) , Blood Collection for PK Testing (15 minutes post injection) , Blood Collection for PK Testing (60 minutes post injection) , Blood Collection for PK Testing (180 minutes post injection) , and Blood Collection for PK Testing (18-20 hours post injection).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

The subject has provided written informed consent with HIPAA (Health Information Portability and Accountability Act) authorization before the initiation of any study-related procedures.
Has a negative urine drug screening for illicit or unprescribed drugs suggestive of drug abuse.
All subjects shall be ≥18 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 4 weeks prior to the consent date.
The subject has moderate to severe RA as determined by the 2010 ACR/EULAR (score of ≥ 6/10).

Key exclusion criteria (9 listed)

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 for a condition other than rheumatoid arthritis.
The subject has renal insufficiency as demonstrated by serum creatinine clearance of < 60 mL/min.
The subject has hepatic insufficiency as demonstrated by ALT or AST greater than two times the upper limit of normal.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Tc99m-tilmanoceptAlso: tilmanoceptTilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.	Drug	Group 1 (RA), Group 2 (RA), Group 3 (RA), Group 4 (RA), Group 5 (RA), Group 6 (RA), Group 7 (RA), Group 8 (RA), Group 9 (RA)
SPECT Imaging (60 Minutes post-injection)Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection.	Procedure or surgery	Group 1 (RA), Group 2 (RA), Group 3 (RA), Group 4 (RA), Group 5 (RA), Group 6 (RA), Group 7 (RA), Group 8 (RA), Group 9 (RA)
SPECT Imaging (180 Minutes post-injection)Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection.	Procedure or surgery	Group 1 (RA), Group 2 (RA), Group 3 (RA), Group 4 (RA), Group 5 (RA), Group 6 (RA), Group 7 (RA), Group 8 (RA), Group 9 (RA)
Whole body planar SPECT imaging (15 Minutes post-injection)Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 15 minutes post-injection for dosimetry.	Procedure or surgery	Group 10 (Healthy Controls), Group 11 (RA)
Whole body planar SPECT imaging (60 Minutes post-injection)Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 60 minutes post-injection for dosimetry.	Procedure or surgery	Group 10 (Healthy Controls), Group 11 (RA)
Whole body planar SPECT imaging (180 Minutes post-injection)Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 180 minutes post-injection for dosimetry.	Procedure or surgery	Group 10 (Healthy Controls), Group 11 (RA)
Whole body planar SPECT imaging (18-20 Hours post-injection)Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 18-20 Hours post-injection for dosimetry.	Procedure or surgery	Group 10 (Healthy Controls), Group 11 (RA)
Blood Collection for PK Testing (15 Mins Before Injection)Blood will be collected for subjects enrolled in Groups 10-11 for the purpose of PK analysis within 15 minutes prior to administration of Tc 99m tilmanocept	Procedure or surgery	Group 10 (Healthy Controls), Group 11 (RA)
Blood Collection for PK Testing (after injection)Blood will be collected for subjects enrolled in Groups 10-11 for the purpose of PK analysis immediately following administration of Tc 99m tilmanocept (00:00)	Procedure or surgery	Group 10 (Healthy Controls), Group 11 (RA)
Blood Collection for PK Testing (15 minutes post injection)Blood will be collected for subjects enrolled in Groups 10-11 for the purpose of PK analysis at 15 ± 5 minutes post injection of Tc 99m tilmanocept	Procedure or surgery	Group 10 (Healthy Controls), Group 11 (RA)
Blood Collection for PK Testing (60 minutes post injection)Blood will be collected for subjects enrolled in Groups 10-11 for the purpose of PK analysis at 60 ± 15 minutes post injection of Tc 99m tilmanocept	Procedure or surgery	Group 10 (Healthy Controls), Group 11 (RA)
Blood Collection for PK Testing (180 minutes post injection)Blood will be collected for subjects enrolled in Groups 10-11 for the purpose of PK analysis at 180 ± 15 minutes post injection of Tc 99m tilmanocept	Procedure or surgery	Group 10 (Healthy Controls), Group 11 (RA)
Blood Collection for PK Testing (18-20 hours post injection)Blood will be collected for subjects enrolled in Groups 10-11 for the purpose of PK analysis at 18-20 hours post injection of Tc 99m tilmanocept	Procedure or surgery	Group 10 (Healthy Controls), Group 11 (RA)
Planar Image with both Hands in Field of ViewSubjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Procedure or surgery	Group 1 (RA), Group 10 (Healthy Controls), Group 11 (RA), Group 2 (RA), Group 3 (RA), Group 4 (RA), Group 5 (RA), Group 6 (RA), Group 7 (RA), Group 8 (RA), Group 9 (RA)

Primary outcome

Incidence of Adverse Drug Reaction
Time frame: From Enrollment to termination, up to 53 days
Number of participants that experienced pharmacologic activity or ADR in each dose group.

12 secondary outcomes

Per Subject Localization Rate of Tc 99m Tilmanocept by SPECT Imaging
Time frame: For Groups 1-9, 60 ± 15 min or 180 ± 15 minute post injection planar and SPECT/CT images are used
Tc 99m Tilmanocept Joint Localization Rate in Rheumatoid Arthritis Identified Joints
Time frame: Whole-body planar scan at 60 ± 15 and 180 ± 15 minutes post Tc 99m tilmanocept administration with a duration of approximately 25 to 30 minutes at each timepoint.
Concordance
Time frame: Qualitative (i.e., visual) assessments of planar images were acquired at the 60 ± 15-minute and 180 ± 15-minute timepoints in Groups 1-9.
Localization Intensity
Time frame: Post-injection imaging at 60±15 and 180±15 min
Per Subject Localization Rate of Tc 99m Tilmanocept in Areas Other Than RA
Time frame: Imaging taken 60 ± 15 min and 180 ± 15 min post-injection
Maximum Observed Concentration (Cmax)
Time frame: 15 minutes prior to administration. Immediately after administration. 15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post administration
Time to Cmax (Tmax)
Time frame: Radioactivity was quantitated at each time point -15 mins prior to administration• Immediately after administration •15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post admi
Area Under the Concentration-time Curve (AUC) From Hour 0 to the Last Measureable Concentration (AUC0-t)
Time frame: Hour 0 to hour 18-20, with time points immediately post injection, 0.25 hr, 1 hr, 3 hr and 18-20 hr after injection
AUC Extrapolated to Infinity
Time frame: 15 mins prior to administration • Immediately after administration • 15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post administration
Apparent Terminal Elimination Rate Constant (Z)
Time frame: 15 mins prior to administration • Immediately after administration • 15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post administration
Apparent Terminal Elimination Half-life (t1/2)
Time frame: 15 mins prior to administration • Immediately after administration • 15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post administration
Radiation Dosimetry of Tc 99m Tilmanocept
Time frame: Planar images were taken 15 ± 5 minutes, 60 ± 5 minutes, 180 ± 5 minutes, 18 to 20 hours after Tc 99m tilmanocept administration and processed in accordance with the NAV3-21 protocol endpoints using established dosimetry software.

Results and safety

Results posted to the registry on 12 Aug 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group 1 (RA)	3	3
Group 2 (RA)	3	3
Group 3 (RA)	3	3
Group 4 (RA)	3	3
Group 5 (RA)	3	3
Group 6 (RA)	3	3
Group 7 (RA)	3	3
Group 8 (RA)	3	3
Group 9 (RA)	3	3
Group 10 (Healthy Controls)	6	6
Group 11 (RA)	6	6

Primary outcome: Incidence of Adverse Drug Reaction

Time frame: From Enrollment to termination, up to 53 days. Count of participants. Unit: Participants

Measure	Group 1 (RA) n = 3	Group 2 (RA) n = 3	Group 3 (RA) n = 3	Group 4 (RA) n = 3	Group 5 (RA) n = 3	Group 6 (RA) n = 3	Group 7 (RA) n = 3	Group 8 (RA) n = 3	Group 9 (RA) n = 3	Group 10 (Healthy Controls) n = 6	Group 11 (RA) n = 6
Value	3	3	3	3	3	3	3	3	3	6	6

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: 53 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1 (RA)	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Group 2 (RA)	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Group 3 (RA)	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Group 4 (RA)	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Group 5 (RA)	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Group 6 (RA)	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3
Group 7 (RA)	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Group 8 (RA)	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3
Group 9 (RA)	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Group 10 (Healthy Controls)	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Group 11 (RA)	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Micheal Blue, MD study director

Navidea Biopharmaceuticals

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Drug Reaction (time frame: From Enrollment to termination, up to 53 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02865434.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2021.