Pharmacokinetics and Dosimetry of Tc 99m Tilmanocept Following a Single Intravenous Dose Administration in Male and Female Subjects Diagnosed With Rheumatoid Arthritis (RA)

A Phase I, Open-Label Study to Investigate the Pharmacokinetics and Dosimetry of Tc 99m Tilmanocept Following a Single Intravenous Dose Administration in Male and Female Subjects Diagnosed With Rheumatoid Arthritis

A prospective, open-label, single center, study to evaluate pharmacokinetics and dosimetry of intravenously injected Tc 99m tilmanocept at three mass doses (50 µg, 200 µg, and 400 µg) radiolabeled with 10 millicuries (mCi) Tc 99m.

Study Overview

• Status: Withdrawn
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Drug: Tilmanocept

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subject has provided written informed consent with HIPAA (Health Information Portability and Accountability Act) authorization before the initiation of any study-related procedures.
2. The subject is 30 - 65 years of age at the time of consent.
3. Has a negative urine drug screening for illicit or unprescribed drugs suggestive of drug abuse.
4. Subjects will have a BMI of 18 to 34 kg/m2, inclusive, at Screening
5. The subject has active RA as determined by the Clinical Disease Activity Index score of ≥ 10 and have ≥ 2 swollen joints.
6. If the subject is receiving methotrexate, they have been at a stable dose for > 4 weeks prior to the Day 1 visit.
7. If the subject is receiving biologic therapy or other DMARDs, they have been at a stable dose > 8 weeks prior to the Day 1 visit.
8. If the subject is receiving NSAIDS or oral corticosteroids, the dose has been at a stable dose for > 4 weeks prior to the Day 1 visit. The corticosteroid dose should be ≤ 10mg/day of prednisone or an equivalent steroid dose.
9. Aside from being diagnosed with rheumatoid arthritis, subjects must be in good health, as determined by medical history, physical examination, vital sign assessment, 12 lead electrocardiogram (ECG) and clinical laboratory evaluations.

Exclusion Criteria:

1. The subject is pregnant or lactating.
2. The subject has a significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the Investigator)
3. The subject has a history of significant hypersensitivity, intolerance, or allergy to dextran or modified forms of dextran; unless approved by the Investigator
4. The subject has a history or presence of an abnormal ECG, which, in the Investigator's opinion, is clinically significant
5. The subject has participated in a radiolabeled investigational study drug trial within 3 months prior to Day 1
6. The subject has exceeded yearly radioactive dose of 30 millisieverts (mSv)
7. The subject has a history of drug abuse or alcohol within 2 years before dose administration, or positive drug or alcohol test at screening.
8. The subject has used tobacco- or nicotine-containing products (including but not limited to cigarettes, e-cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to Day 1, or positive cotinine screen
9. The subjects uses any prescription medications within 14 days prior to Day 1, except as allowed by the inclusion criteria or as deemed acceptable by the Investigator;
10. The subject uses any over-the-counter, non-prescription preparations (including vitamins, minerals, and phytotherapeutic/ herbal/plant-derived preparations) within 7 days prior to Day 1, unless deemed acceptable by the Investigator;
11. The subject has poor peripheral venous access;
12. The subject has donated blood within 30 days prior to Day 1, or plasma within 2 weeks prior to Day 1
13. The subject has received blood products within 2 months prior to Day 1;
14. The subject has any acute or chronic condition that, in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in this clinical study.
15. The subject has received any radiopharmaceutical within 7 days prior to the administration of Tc 99m tilmanocept.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 50 ug Tilmanocept; Single dose of 50 ug tilmanocept radiolabeled with 10 mCi technetium Tc99m	Drug: Tilmanocept; Intravenously administered Technetium Tc 99m tilmanocept
Experimental: 200 ug Tilmanocept; Single dose of 200 ug tilmanocept radiolabeled with 10 mCi technetium Tc99m	Drug: Tilmanocept; Intravenously administered Technetium Tc 99m tilmanocept
Experimental: 400 ug Tilmanocept; Single dose of 400 ug tilmanocept radiolabeled with 10 mCi technetium Tc99m	Drug: Tilmanocept; Intravenously administered Technetium Tc 99m tilmanocept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma concentration (Cmax) of Technetium Tc 99m Tilmanocept	Maximum Plasma concentration (Cmax) of Technetium Tc 99m Tilmanocept	1 Days
Plasma Area Under the Curve (AUC) of Technetium Tc 99m Tilmanocept	Plasma Area Under the Curve (AUC) of Technetium Tc 99m Tilmanocept	2 Days
Systemic Clearance (CLs) of Technetium Tc 99m Tilmanocept	Systemic Clearance (CLs) of Technetium Tc 99m Tilmanocept	3 Days
Renal Clearance (CLr) of Technetium Tc 99m Tilmanocept	Renal Clearance (CLr) of Technetium Tc 99m Tilmanocept	2 days
Terminal Elimination Half-Life (T1/2) of Technetium Tc 99m Tilmanocept	Terminal Elimination Half-Life (T1/2) of Technetium Tc 99m Tilmanocept	3 days
Clinical Dosimetry of Technetium Tc 99m Tilmanocept	Clinical Dosimetry of Technetium Tc 99m Tilmanocept	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events	Incidence of Adverse Events	7 Days

Collaborators and Investigators

• Sponsor: Navidea Biopharmaceuticals

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2017
• Primary Completion (Anticipated): January 1, 2018
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: July 25, 2017
• First Submitted That Met QC Criteria: August 2, 2017
• First Posted (Actual): August 7, 2017

Study Record Updates

• Last Update Posted (Actual): October 9, 2018
• Last Update Submitted That Met QC Criteria: October 4, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: NAV3-26

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No