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
1 other identifier
interventional
39
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jan 2017
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 5, 2016
CompletedFirst Posted
Study publicly available on registry
August 12, 2016
CompletedStudy Start
First participant enrolled
January 1, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2018
CompletedResults Posted
Study results publicly available
August 12, 2021
CompletedAugust 12, 2021
August 1, 2021
1.4 years
August 5, 2016
September 15, 2020
August 11, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of Adverse Drug Reaction
Number of participants that experienced pharmacologic activity or ADR in each dose group.
From Enrollment to termination, up to 53 days
Secondary Outcomes (12)
Per Subject Localization Rate of Tc 99m Tilmanocept by SPECT Imaging
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
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
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
Post-injection imaging at 60±15 and 180±15 min
Per Subject Localization Rate of Tc 99m Tilmanocept in Areas Other Than RA
Imaging taken 60 ± 15 min and 180 ± 15 min post-injection
- +7 more secondary outcomes
Study Arms (11)
Group 1 (RA)
EXPERIMENTALGroup 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)
EXPERIMENTALGroup 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)
EXPERIMENTALGroup 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)
EXPERIMENTALGroup 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)
EXPERIMENTALGroup 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)
EXPERIMENTALGroup 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)
EXPERIMENTALGroup 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)
EXPERIMENTALGroup 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)
EXPERIMENTALGroup 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)
EXPERIMENTALGroup 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)
EXPERIMENTALGroup 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).
Interventions
Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
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.
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.
Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 15 minutes post-injection for dosimetry.
Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 60 minutes post-injection for dosimetry.
Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 180 minutes post-injection for dosimetry.
Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 18-20 Hours post-injection for dosimetry.
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 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 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 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 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 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
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Kettering Medical Center
Kettering, Ohio, 45429, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Bonnie Abbruzzzese
- Organization
- Navidea Biopharmaceuticals
Study Officials
- STUDY DIRECTOR
Micheal Blue, MD
Navidea Biopharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 5, 2016
First Posted
August 12, 2016
Study Start
January 1, 2017
Primary Completion
June 1, 2018
Study Completion
June 1, 2018
Last Updated
August 12, 2021
Results First Posted
August 12, 2021
Record last verified: 2021-08
Data Sharing
- IPD Sharing
- Will not share