Proof-of-concept Study With NVDX3 for Treatment of Distal Radius Fractures.

Study Overview
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Brief Summary
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Prospective, single arm, monocentric clinical study to test NVDX3 in patients suffering from distal radius fracture. NVDX3 will be implanted during a single surgical intervention.

Detailed Description
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This is a prospective, single arm, monocentric first-in-human PoC study in adult patients, suffering from a distal radius fracture, treated during the surgical intervention with NVDX3, an osteogenic implant from human allogeneic origin. As per standard of care, patients with DRF are followed up to 3 months post-intervention. In the context of this trial, patient safety and IMP efficacy will be followed up to 12 months post-implant surgery.

Official Title
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A First-in-human Proof-of-concept Study With NVDX3, an Osteogenic Implant of Human Allogenic Origin, in the Treatment of Distal Radius Fractures in Adults.

Conditions
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Distal Radius Fractures

Intervention / Treatment
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* Drug: NVDX3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients within the age range of ≥18 years to ≤80 years. Patient diagnosed with DRF with confirmed: Classification AO/ATO: C2 and C3 - Intra-articular & multifragmentation. Estimated volume of the targeted bone void should not exceed 5cc. Availability of diagnostic AP and LAT X-ray or CT scan. Patient can undergo the targetted surgical intervention within 7 days post-DRF diagnosis. Patient fulfills criteria for undergoing a surgical intervention. Patient has understood and accepted to participate in the study according to all study procedures by signing the informed consent. Exclusion Criteria: Open DRF or closed DRF with increased infection risk. Injury to the median nerve. Previous fracture of the target distal radius. Documented disease limiting mobility and functional assessments (eg. Grip strength test). Dependency on crutches or any comparable walking aids. Patient is overweight, has a BMI ≥35. Presence of clinically significant infection at the target implant site or systemic infection. History of allergic reaction or any anticipated hypersensitivity to any of the anticipated: Osteosynthesis materials (PEEK plate and screws). Anesthetic agents. Components of the NVDX3 implant. Presence of any auto-immune disease, with exception of well controlled diabetes type-1 or II, or auto-immune thyroid disorders. Positive serology for human immunodeficiency virus (HIV), HBcAb and/or HBsAg. Presence of an active tumor. Documented metabolic bone disease or any disorder, such as but not limited to high-risk osteoporosis, that could interfere with the bone healing and bone metabolism. Chronic, ongoing, or planned use of medications that might affect bone metabolism or bone quality such as bisphosphonates, steroids, methotrexate, anticoagulants, immunosuppressants or immunotherapy. Excessive smoking, history of chronic alcohol or drug abuse within the 12 months prior to screening. Any history of experimental therapy with another investigational drug within 60 days prior to screening. Pregnant women or women of childbearing potential (WOCBP) not agreeing to use an effective method of birth control3 during the course of the study. Note: WOCBP including peri-menopausal women who have had a menstrual period within 1 year prior to surgery have to have a negative pregnancy test before entering in the study. Any other psychosocial, mental and physical condition which, in the opinion of the investigator, could interfere with the trial conduct, the patient's compliance or influence interpretation of the results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NVDX3 implant<br> | Drug: NVDX3<br>* NVDX3 is implanted during a single surgical intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Endpoint: evaluation of SAEs and NVDX3 related AEs | Evaluation of all SAEs and NVDX3 related AEs | Between screening (V1) and 12-months post- IS (V8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: all acute SAEs and NVDX3 related AEs | Description of all acute SAEs and NVDX3 related AEs | Between screening (V1) and 6 weeks post-IS (V5) | 
| Safety: all SAEs and NVDX3 related AEs | Description of all SAEs and NVDX3 related AEs | Beyond 6 weeks (V5 excluded) until 12 months post-IS | 
| Safety: TEAEs | Description of Treatment Emergent AEs (TEAEs) | a. Between screening and week 6 (V5 included) b. Between week 6 (V5 excluded) till month 12 (V8 included) c. through study completion | 
| Safety: related and unexpected (S)AEs | Description of related and unexpected (S)AEs | Between inclusion and 13 months post-IS | 
| Safety: AESI | Description of AE of Special Interest (AESI) | Between inclusion and 13 months post-IS | 
| Safety: lab data | Description of lab data | Between inclusion and 13 months post-IS | 
| Safety: vital signs | Description of vital signs: body temperature, pulse rate, respiratory rate and blood pressure | Between inclusion and 13 months post-IS | 
| Efficacy: Radiological assessments on Computed Tomography (CT) data using the extended Lane and Sandhu Scoring tool (eLSS) | Radiological assessments on Computed Tomography data (CT) using the extended Lane and Sandhu Scoring tool (eLSS) compared to HD: evaluation of bone formation, union and remodeling status and evaluation of total extended Lane and Sandhu Score | At 3 and 12-months post-IS | 
| Efficacy: Radiological assessments on X-ray using the eLSS tool | Radiological assessments on X-ray using the eLSS tool compared to the peri-operative x-ray acquisitions: evaluation of bone formation, union and remodeling status and evaluation of total extended Lane and Sandhu Score | At HD, 2-, 6-weeks, 3-,6- and 12-months post-IS | 
| Efficacy: Clinical assessments | Following clinical assessment will be performed compared to HD: Grip strength measure with a hydraulic hand dynamometer | At 2-,6 weeks, 3-, 6-, and 12-months post- IS | 
| Efficacy: Clinical assessments | Following clinical assessment will be performed compared to HD: Modified Mayo Wrist Score (MMWS): A physician-based scoring evaluating the patients' pain, active flexion/extension arc, grip strength and ability to return to regular employment or activities. | At 2-,6 weeks, 3-, 6-, and 12-months post- IS | 
| Efficacy: Clinical assessments | Following clinical assessment will be performed compared to HD: PRWE Questionnaire: A patient reported scoring evaluating the patients' wrist pain and disability | At 2-,6 weeks, 3-, 6-, and 12-months post- IS | 
| Efficacy: NRS-pain | NRS-pain, a patient reported scoring evaluating the patients' pain compared to Screening | At HD, 2-,6 weeks, 3-, 6-, and 12-months post-IS | 
| Exploratory: Radiological assessments on Dual Energy CT data (DECT) | Explore non-conventional evaluation methods using CT and Dual Energy Computed Tomography (DECT) imaging, compared to HD, including but not limited to NVDX3 density. | At 3-, and 12-months post-IS | 
| Exploratory: Radiological assessments on Dual Energy CT data (DECT) | Explore non-conventional evaluation methods using CT and Dual Energy Computed Tomography (DECT) imaging, compared to HD, including but not limited to the composition of NVDX3. | At 3-, and 12-months post-IS | 
| Exploratory: Radiological assessments on Dual Energy CT data (DECT) | Explore non-conventional evaluation methods using CT and Dual Energy Computed Tomography (DECT) imaging, compared to HD, including but not limited to the composition of surrounding tissue. | At 3-, and 12-months post-IS | 
| Exploratory: Radiological assessments on Dual Energy CT data (DECT) | Explore non-conventional evaluation methods using CT and Dual Energy Computed Tomography (DECT) imaging, compared to HD, including but not limited to bone mineral density of native bone. | At 3-, and 12-months post-IS |