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

• Register: ClinicalTrials.gov
• Last refreshed on: 24 August 2021
• Main ID: NCT02865434
• Date of registration: 05/08/2016
• Prospective Registration: Yes
• Primary sponsor: Navidea Biopharmaceuticals
• Public title: Evaluating Safety of Escalating Doses of Tilmanocept by IV Injection and SPECT Imaging in Subjects With and Without RA
• Scientific 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
• Date of first enrolment: January 2017
• Target sample size: 39
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02865434
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Diagnostic. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Micheal Blue, MD
• Affiliation: Navidea Biopharmaceuticals

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Arthritis, Rheumatoid

Intervention(s)

Procedure: Whole body planar SPECT imaging (60 Minutes post-injection)

Drug: Tc99m-tilmanocept

Procedure: Blood Collection for PK Testing (15 Mins Before Injection)

Procedure: Whole body planar SPECT imaging (15 Minutes post-injection)

Procedure: Whole body planar SPECT imaging (18-20 Hours post-injection)

Procedure: Blood Collection for PK Testing (60 minutes post injection)

Procedure: Blood Collection for PK Testing (15 minutes post injection)

Procedure: Blood Collection for PK Testing (18-20 hours post injection)

Procedure: SPECT Imaging (60 Minutes post-injection)

Procedure: Whole body planar SPECT imaging (180 Minutes post-injection)

Procedure: Planar Image with both Hands in Field of View

Procedure: SPECT Imaging (180 Minutes post-injection)

Procedure: Blood Collection for PK Testing (180 minutes post injection)

Procedure: Blood Collection for PK Testing (after injection)

Primary Outcome(s)

Incidence of Adverse Drug Reaction [Time Frame: From Enrollment to termination, up to 53 days]

Secondary Outcome(s)

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.]

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]

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]

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]

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]

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]

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]

Localization Intensity [Time Frame: Post-injection imaging at 60±15 and 180±15 min]

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.]

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]

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.]

Secondary ID(s)

NAV3-21

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 12/08/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02865434