Clinical Study to Evaluate Adaptos®Ortho Wedge Bone Graft Substitute in High Tibial Osteotomy

Study Overview
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Brief Summary
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The aim of this study is to obtain performance and safety data of the new investigational device, dual-part Adaptos®Ortho Wedge, for its intended use in orthopaedic surgery. The study intervention is medial open wedge high tibial osteotomy (OWHTO) with loadbearing plate fixation, where a bone graft substitute material Adaptos®Ortho Wedge is evaluated when used as a bone void filler. Investigational device is expected to support bone formation in osteotomy gap and to resorb in the body. The comparator arms are treated with medial OWHTO with plate fixation, either without a bone graft (the bone defect is left empty, non-augmented osteotomy) or by using a comparator product (chronOS® Wedge, semi-circular) as a bone void filler.

Detailed Description
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The study aims to evaluate the clinical performance and safety of Adaptos®Ortho Wedge (Biomendex Oy) bone graft material, when used for filling the medial osteotomy gap of the knee during OWHTO surgery. This is partially randomized, subject and outcome assessor-blinded, controlled, multi-center study. The total study duration for each patient is planned to be 12 months. In total 6 visits per patient are scheduled in this study. The study has three arms, and patients of all study arms are treated with medial OWHTO surgery to treat unicompartmental medial misalignment of the knee. Participants in the experimental arm (Arm 1) receive the investigational device, the osteotomy gap is filled with Adaptos®Ortho Wedge bone graft substitute. Participants in the control arm (Arm 2) receive the OWHTO treatment, where the osteotomy gap is left empty (no bone graft). Participants in the comparator device arm (Arm 3) receive the OWHTO treatment, where the osteotomy gap is filled with chronOS® Wedge bone graft substitute. In all three groups the metallic fixation plate (TomoFix®) is used for load bearing and for stabilizing the defect. The study device chronOS® Wedge (DePuy Synthes) and TomoFix® (DePuy Synthes) are CE-marked. The products are used within the indication. The subject will be followed for twelve months following OWHTO.The radiological bone regeneration in the bony defect will be assessed at 6-weeks and 3-, 6-, and 12-months post-surgery.

Official Title
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Clinical Study to Evaluate Adaptos®Ortho Wedge Bone Graft Substitute in High Tibial Osteotomy: A Randomized, Controlled, Partially Blinded, Multi-Center Trial.

Conditions
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Knee Deformity

Intervention / Treatment
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* Device: Adaptos®Ortho Wedge (bone grafting surgery)
* Procedure: OWHTO without bone grafting
* Device: chronOS® Wedge (bone grafting surgery)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged between 25 and less than 60 years at the time of enrolment. Subjects that sign and date a written, informed consent form (ICF) prior to the initiations of any trial procedures, after the nature of the trial has been explained according to regulatory requirements. Subjects who can comply with trial procedures and are available for the duration of the trial. Accepts all treatment arms. Subjects with varus malalignment of the knee, scheduled to have medial open-wedge high tibial osteotomy (OWHTO) but are otherwise in good health at the time of entry into the trial as determined by medical history, physical/clinical examination, and clinical judgement of the investigator. Full knee range of motion (ROM) (at least 5-120 degrees). Preoperatively planned osteotomy 5-13 degrees of the proximal tibia done based on the weight-bearing x-ray of the full leg in AP view using Miniaci Method. Body Mass Index (BMI) ≤30 Exclusion Criteria: Previous knee area osteotomy or lower limb arthroplasty of the investigational knee. Presence of the following unfavourable conditions: osteoporosis, infectious/inflammatory joint disease, infections, or inflammation in the operation area, clinically relevant, not medically managed, severe acute or chronic medical illness, immune-compromised, metabolic/systemic bone disorder, untreated malignant myeloma, Burkitt's lymphoma Smoking Inability to follow the procedures of the study, e.g. due to language problems, dementia, psychiatric disorder or behaviour etc. of the participant Recent history of substance abuse (ie, recreational drugs, alcohol) that would preclude reliable assessment. Women who are pregnant or breast feeding or planning to become pregnant during the study. Any use of estrogens, estrogen-progestin therapy, or selective estrogens receptor modulators (SERMs) 3 months prior to and after the surgery. Any use of calcitonin, bisphosphonates or recombinant PTH 1-34, 1-84 or other PTH fragments/analogues 6 months prior to surgery or during the study (12 months po). Enrolment of the investigator, his/her family members, employees, and other dependent persons. Involved in study of another investigational product that may affect outcome.

Ages Eligible for Study
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Minimum Age: 25 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adaptos®Ortho Wedge<br>Bone augmentation after Open Wedge High Tibial Osteotomy (OWHTO), with Adaptos®Ortho Wedge (Biomendex Oy, synthetic bone graft material) in combination with a load bearing TomoFix® Medial High Tibia Plate (DePuy Synthes). | Device: Adaptos®Ortho Wedge (bone grafting surgery)<br>* After screening and enrollment, subjects will undergo medial knee open wedge high tibial osteotomy (OWHTO) with load bearing locking plate fixation. A synthetic bone graft will be used as a bone void filler in the osteotomy defect. Follow-up visits will be at 6 weeks, 3 months, 6 months, and 10 months.<br>|
| Sham Comparator: No bone graft<br>OWHTO with unfilled bony defect of the osteotomy gap with a load bearing TomoFix® Medial High Tibia Plate (DePuy Synthes). | Procedure: OWHTO without bone grafting<br>* After screening and enrollment, subjects will undergo medial knee open wedge high tibial osteotomy (OWHTO) with load bearing locking plate fixation, without bone grafting. Follow-up visits will be at 6 weeks, 3 months, 6 months, and 10 months.<br>|
| Active Comparator: chronOS® Wedge<br>Bone augmentation, after OWHTO, with chronOS® Wedge (DePuy Synthes, synthetic beta-TCP bone graft) in combination with a load bearing TomoFix® Medial High Tibia Plate (DePuy Synthes). | Device: chronOS® Wedge (bone grafting surgery)<br>* After screening and enrollment, subjects will undergo medial knee open wedge high tibial osteotomy (OWHTO) with load bearing locking plate fixation. A synthetic bone graft will be used as a bone void filler in the osteotomy defect. Follow-up visits will be at 6 weeks, 3 months, 6 months, and 10 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic bone regeneration of the osteotomy defect, comparison between three treatment arms. | Radiographic bone regeneration assessments of the native x-ray of the standing anteroposterior (AP) radiographs of the knee, evaluated in the mediolaterally divided five zones of the osteotomized gap area (Brosset 2011), with rating of six bone remodeling phases (phases 0-5, with the score of 5 for the best outcome). Assessment longitudinally at 6-weeks and repeatedly at 3-, 6-, and 12-months post-surgery. The change between the treatment arms is compared considering all time points assessed. | Change from baseline to 12 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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synthetic bone graft, Adaptos, high tibial osteotomy, orthopaedics