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

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

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.

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.

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.