Clinical trial NCT02865434: Evaluating Safety of Escalating Doses of Tilmanocept by IV Injection and SPECT Imaging in Subjects With and Without RA
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Arthritis, Rheumatoid
Lead sponsor: Navidea Biopharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-08-12
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

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.

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.

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: Incidence of Adverse Drug Reaction
timeFrame: From Enrollment to termination, up to 53 days
Secondary outcomes:
measure: Per Subject Localization Rate of Tc 99m Tilmanocept by SPECT Imaging
timeFrame: For Groups 1-9, 60 ± 15 min or 180 ± 15 minute post injection planar and SPECT/CT images are used
measure: Tc 99m Tilmanocept Joint Localization Rate in Rheumatoid Arthritis Identified Joints
timeFrame: 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.
measure: Concordance
timeFrame: Qualitative (i.e., visual) assessments of planar images were acquired at the 60 ± 15-minute and 180 ± 15-minute timepoints in Groups 1-9.
measure: Localization Intensity
timeFrame: Post-injection imaging at 60±15 and 180±15 min
measure: Per Subject Localization Rate of Tc 99m Tilmanocept in Areas Other Than RA
timeFrame: Imaging taken 60 ± 15 min and 180 ± 15 min post-injection
measure: Maximum Observed Concentration (Cmax)
timeFrame: 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
measure: Time to Cmax (Tmax)
timeFrame: 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
measure: Area Under the Concentration-time Curve (AUC) From Hour 0 to the Last Measureable Concentration (AUC0-t)
timeFrame: 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
measure: AUC Extrapolated to Infinity
timeFrame: 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
measure: Apparent Terminal Elimination Rate Constant (Z)
timeFrame: 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
measure: Apparent Terminal Elimination Half-life (t1/2)
timeFrame: 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
measure: Radiation Dosimetry of Tc 99m Tilmanocept
timeFrame: 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.
Other outcomes:
Locations:
city: Kettering
country: United States
facility: Kettering Medical Center
state: Ohio
Study officials:
affiliation: Navidea Biopharmaceuticals
name: Micheal Blue, MD
role: STUDY_DIRECTOR
References: