Assessment of 99mTc-NTP 15-5 Uptake on Cartilage, a New Proteoglycan Tracer

Study Overview
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Brief Summary
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This study is a phase I clinical trial aimed to determine the recommended dose of 99mTc-NTP 15-5 to obtain the best tracer joints contrast on images without any toxicity.

Official Title
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Assessment of 99mTc-NTP 15-5 Uptake on Cartilage, a New Proteoglycan Tracer: Phase I Clinical Trial

Conditions
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Osteoarthritis, Knee, Breast Cancer

Intervention / Treatment
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* Drug: 99mTc-NTP 15-5 at a diagnostic activity of 5 MBq/kg
* Drug: 99mTc-NTP 15-5 at a diagnostic activity of 10 MBq/kg
* Drug: 99mTc-NTP 15-5 at a diagnostic activity of 15 MBq/kg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria specific to group 1: - Patient with painful unilateral osteoarthritis of the knee as femorotibial pattern defined by a radiographic score of 0/1 from Kellgren / Lawrence and an average WOMAC score> or equal to 4 and by minor disorders at MRI (MOCART 2.0 score> 70). Inclusion criteria specific to group 2: Patient with non-metastatic breast cancer, hormone receptor positive, HER2 negative, with indication for adjuvant therapy with aromatase inhibitor; treatment not yet started. Age <60 years Common inclusion criteria: Patient with at least 31 healthy joints (based on clinical assessment) signed written informed consent. Affiliation to a health insurance scheme. For women of childbearing age : negative serum pregnancy test at inclusion (less than 7 days prior injection of 99mTc-NTP 15-5). Willing and able to comply with study visits, treatment, exams and the protocol. Exclusion Criteria: Patients <18 years of age. Pregnant or lactating patient. BMI> 30 History of known allergy to excipients contained in the solution of 99mTc-NTP 15-5 Chronic inflammatory rheumatism (rheumatoid arthritis, spondyloarthropathy, psoriatic arthritis, etc.) diffuse arthritis (at least 3 joints affected), autoimmune connectivitis, fibromyalgia. Known chronic joint pathology: osteoarthritis affecting at least 3 joints, autoimmune disease, inflammatory rheumatism (except unilateral knee arthritis). Persons deprived of their liberty, under guardianship / curatorship, or safeguard of justice. Treatment with NSAIDs or cessation of less than 48 h. Inability to comply with medical requirement / follow-up of the trial for geographic, family, social or psychological reasons. These conditions should be discussed with the patient before registration in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: dose escalation model
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 99mTc-NTP 15-5 (level 1)<br>99mTc-NTP 15-5 at a diagnostic activity of 5 MBq/kg | Drug: 99mTc-NTP 15-5 at a diagnostic activity of 5 MBq/kg<br>* 1 intravenous injection of 99mTc-NTP 15-5 at a diagnostic activity of 5 MBq/kg (D0)<br>|
| Experimental: 99mTc-NTP 15-5 (level 2)<br>99mTc-NTP 15-5 at a diagnostic activity of 10 MBq/kg | Drug: 99mTc-NTP 15-5 at a diagnostic activity of 10 MBq/kg<br>* 1 intravenous injection of 99mTc-NTP 15-5 at a diagnostic activity of 10 MBq/kg (D0)<br>|
| Experimental: 99mTc-NTP 15-5 (level 3)<br>99mTc-NTP 15-5 at a diagnostic activity of 15 MBq/kg | Drug: 99mTc-NTP 15-5 at a diagnostic activity of 15 MBq/kg<br>* 1 intravenous injection of 99mTc-NTP 15-5 at a diagnostic activity of 15 MBq/kg (D0)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| determination of the recommended dose of 99mTc-NTP 15-5 to obtain the best tracer joints contrast on images without any toxicity | defined as the dose from which 100% of patients will present a score 3 (semi-quantitative visual scale on whole body imaging) in at least 80% of healthy joints visualized on scintigraphies performed 2 h or less post-injection and without dose-limiting toxicity (DLT). | Imaging at Day 0 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours post-injection) | 
| dose-limiting toxicity (DLT) | defined as any grade 3-4 toxicity according to the NCI-CTCAE (version 4.03) | 1 week after injection of the 99mTc-NTP 15-5 (Day 0) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3D quantification analysis | TEMP Volumetric regions of interest (VOI) will be centered on cartilaginous zones, and on the corresponding bony diaphyses or vertebral body or the adjacent muscles. The articular uptake of 99mTc NTP-15-5 will thus be normalized to bone or muscle uptake. | imaging at Day 0, 30 minutes, 2 hours, 4 hours, 6-8 hours after injection of the 99mTc-NTP 15-5 | 
| Safety of 99mTc-NTP 15-5 (frequence of adverse events) | according to the NCI-CTCAE (version 4.03) | 1 week after injection of the 99mTc-NTP 15-5 (Day 0) | 
| Biodistribution of 99mTc-NTP 15-5 | evaluated by measuring the percentage of injected activity of 99mTc-NTP 15-5 fixed on the target organs and on the pathological joints or healthy joints. | imaging at Day 0, 30 minutes, 2 hours, 4 hours, 6-8 hours after injection of the 99mTc-NTP 15-5 | 
| Pharmacokinetics of 99mTc-NTP 15-5 by assessment of Area Under the Curve (AUC) | radiation counting on whole blood and on plasma | at Day 0 during the first 8 hours after injection of the 99mTc-NTP 15-5 | 
| Pharmacokinetics of 99mTc-NTP 15-5 by assessment of Maximum Concentration (Cmax) | radiation counting on whole blood and on plasma | at Day 0 during the first 8 hours after injection of the 99mTc-NTP 15-5 | 
| Pharmacokinetics of 99mTc-NTP 15-5 by assessment of the time take to reach Cmax (Tmax) | radiation counting on whole blood and on plasma | at Day 0 during the first 8 hours after injection of the 99mTc-NTP 15-5 | 
| Urinary elimination of 99mTc-NTP 15-5 | by counting | at Day 0 during the first 8 hours after injection of the 99mTc-NTP 15-5 | 
| Dosimetry | measurement of the absorbed dose per organ will be evaluated by quantitative analysis. | imaging at Day 0, 30 minutes, 2 hours, 4 hours, 6-8 hours after injection of the 99mTc-NTP 15-5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cartilage, proteoglycan tracer