Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Lymphoseek, Tc99m-tilmanocept
Tilmanocept · 8 trials · 7 indications
The proportion of lymph nodes detected intraoperatively by blue dye that were also detected by Lymphoseek.
The normal limits of TUVjoint (on a per joint basis) in HC subjects, which are defined as the 5 and 95 percentiles of TUVjoint of bilateral joints (i.e., bilateral wrists, metacarpophalangeal joint \[MCPs\], proximal interphalangeal \[PIPs\]).
Presence/absence of tilmanocept localization in the hands and wrists will be summarized with frequency counts and percentages by reader and joint.
The camera-specific precision of TUVjoint in subjects with active RA and Healthy Controls (HCs), which is described as the Root Mean Square Difference (RMSD) between the 15-minute planar images (referred to as A and B images at 60 and 180 minutes). The RMSD is calculated as the square root of the mean squared deviation from zero.
The stability of the mean/variance relationship, which is assessed by comparing the Coefficient of Variation (CV) of TUVjoint and TUVglobal in subjects with active RA and in healthy control subjects at 60 and 180 minutes.
The Kendall rank correlation of the change in global TUV from baseline to 5 weeks (ΔTUVglobal\[5w\]) and response to new anti-TNFα bDMARD therapy defined by the change from baseline of CDAI to 12 ± 1 weeks and 24 ± 1 weeks (ΔCDAI12w and ΔCDAI24w).• The Kendall rank correlation of ΔTUVglobal\[5w\] and response to new anti-TNFα bDMARD therapy from baseline to 12 ± 1 weeks and 24 ± 1 weeks defined by ACR Response Criteria (ΔACR12w and ΔACR24w)
Longitudinal (8-day) variation of TUV analyzed for each DAS28 joint, defined as the root mean square deviation (RMSD) and 95% confidence interval for the RMSD for each joint at Day 0 vs Day 8
Count of subjects with a localization by Tc 99m tilmanocept by imaging. Localization is based on the use of SPECT imaging and defined as the accumulation of radioactivity at intensity greater than background.
Number of participants that experienced pharmacologic activity or ADR in each dose group.
Cohort 1 (100 mcg/ 5mCi) was conducted first. A safety data review meeting was held after completion of Cohort 1 and again after completion of Cohort 2 at which the principal investigators and sponsor representatives reviewed the safety data to determine whether to proceed to the next cohort. All cohorts were evaluated for safety. Safety evaluations included AEs, clinical laboratory tests, vital signs, physical examinations, and ECGs. The data table includes the number of safety signals detected during the evaluation for each cohort.
The primary endpoint was to compare the cumulative total of anatomical zones of active RA (which were clinically defined by a swollen/tender classification during the DAS28 joint count assessment performed at baseline) with Tc 99m tilmanocept localization observed at 2-3 hours and at 4-6 hours after administration on Day 1. Tc 99m tilmanocept localization is defined by accumulation of radioactivity at an intensity greater than background, which was qualitatively determined by the central reader's visual assessment of the acquired images .
| Arm | Type | Description |
|---|---|---|
| Lymphoseek, Lymphatic mapping, Injection | EXPERIMENTAL | - |
| Subjects Free of Inflammatory Disease | EXPERIMENTAL | The first arm will be comprised of HCs who are deemed to be clinically free of inflammatory diseases, arthropathies, and/or arthroplasties and clinically free of joint pain for at least 28 days prior to the consent date. |
| Healthy Controls and RA Subjects on Stable Therapy | EXPERIMENTAL | The second arm is comprised of \[1\] disease-free HCs and \[2\] clinically diagnosed RA subjects on stable treatment. |
| RA subjects on stable therapy | EXPERIMENTAL | Arm 2 includes clinically-diagnosed RA subjects on stable treatment. Arm 2 was designed to evaluate image/re-image and test re-test (i.e., repeated dose) consistency of joint-specific and global TUVs across a variety of image acquisition intervals. |
| RA subjects who are candidates for initiation of a new anti-TNFα therapy | EXPERIMENTAL | Arm 3 includes clinically-diagnosed RA subjects on stable treatment who are candidates for initiation of, or change to, new anti-TNFα therapy. Arm 3 was designed to assess the efficacy of global TUVs, obtained before and after initiation of a new anti-TNFα therapy, to predict future clinical responsiveness to the new therapy. |
| Tc 99m tilmanocept | EXPERIMENTAL | Subjects who are enrolled and will receive 50 micrograms tilmanocept radiolabeled with 2 millicuries of Tc 99m and undergo serial SPECT or SPECT/CT imaging. |
| Group 1 (RA) | EXPERIMENTAL | Group 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) | EXPERIMENTAL | Group 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) | EXPERIMENTAL | Group 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) | EXPERIMENTAL | Group 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) | EXPERIMENTAL | Group 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) | EXPERIMENTAL | Group 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) | EXPERIMENTAL | Group 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) | EXPERIMENTAL | Group 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) | EXPERIMENTAL | Group 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) | EXPERIMENTAL | Group 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) | EXPERIMENTAL | Group 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). |
| 100 mcg/5 mCi Tc99m-Tilmanocept | EXPERIMENTAL | Four subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 5 mCi. |
| 100 mcg/10 mCi Tc99m-Tilmanocept | EXPERIMENTAL | Four subjects will receive a single IV injection of 100 micrograms of Tc99m tilmanocept radiolabeled with 10 mCi. |
| 200 mcg/5 mCi Tc99m-Tilmanocept | EXPERIMENTAL | Up to six subjects will receive a single subcutaneous injection and a single IV injection of 200 micrograms of Tc99m tilmanocept radiolabeled with 5 mCi. |
| Cohort 1 | OTHER | Healthy Volunteers: 50 mcg tilmanocept with 2 millicuries (mCi) Tc 99m |
| Cohort 2 | OTHER | Healthy Volunteers: 200 mcg tilmanocept with 2 mCi Tc 99m |
| Cohort 3 | EXPERIMENTAL | RA Group: 50 mcg tilmanocept with 2 mCi Tc 99m |
| Cohort 4 | EXPERIMENTAL | RA group:200 mcg tilmanocept with 2 mCi Tc 99m |
| Name | Type | Description |
|---|---|---|
| Lymphoseek | DRUG | The total volume of Lymphoseek injection will be between 0.1 - 1.0 mL. |
| Tc99m tilmanocept | DRUG | Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. |
| Tc 99m tilmanocept | DRUG | Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. |
| Tc99m-tilmanocept | DRUG | Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. |
| SPECT Imaging (60 Minutes post-injection) | PROCEDURE | 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. |
| SPECT Imaging (180 Minutes post-injection) | PROCEDURE | 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. |
| Whole body planar SPECT imaging (15 Minutes post-injection) | PROCEDURE | Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 15 minutes post-injection for dosimetry. |
| Whole body planar SPECT imaging (60 Minutes post-injection) | PROCEDURE | Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 60 minutes post-injection for dosimetry. |
| Whole body planar SPECT imaging (180 Minutes post-injection) | PROCEDURE | Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 180 minutes post-injection for dosimetry. |
| Whole body planar SPECT imaging (18-20 Hours post-injection) | PROCEDURE | Subjects enrolled in Groups 10-11 will receive a whole body planar SPECT scan performed 18-20 Hours post-injection for dosimetry. |
| Blood Collection for PK Testing (15 Mins Before Injection) | PROCEDURE | 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 Collection for PK Testing (after injection) | PROCEDURE | 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 Collection for PK Testing (15 minutes post injection) | PROCEDURE | 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 Collection for PK Testing (60 minutes post injection) | PROCEDURE | 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 Collection for PK Testing (180 minutes post injection) | PROCEDURE | 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 Collection for PK Testing (18-20 hours post injection) | PROCEDURE | 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 |
| Planar Image with both Hands in Field of View | PROCEDURE | 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. |
| Tilmanocept | DRUG | - |
Inclusion Criteria: 1. The patient has provided written informed consent with HIPAA authorization. 2. The patient is a candidate for surgical intervention, with lymph node mapping being a part of the surgical plan. 3. The patient is at least 18 years of age at the time of consent. 4. The patient ha...
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