Prospective Validation Study of the CD8+TEMRA Cells As a Prognostic Biomarker of Healing Outcome After Fracture

The aim is to identify high-risk patients before the initial operation based on their immunological profile and to be able to provide them with an improved, individualised therapeutic strategy. There are already a large number of approved therapeutic options that are currently only used in revision cases because, among other things, preoperative diagnostics and prognostics are lacking. Furthermore, a sufficient preoperatively determined biomarker would form the basis for the development of new therapeutic approaches, which represent a low cost-benefit and risk-benefit ratio.

The prospective biomarker validation study is applied in a routine-adapted procedure, i.e. all visits are part of the clinical radiological and functional routine checks. Blood sampling on arrival at the hospital will be used to determine the preoperative value of CD8+TEMRA cells. The healing process will be recorded using X-ray/CT images, radiological scores and functional clinical examinations as well as the SF-36. The 1st study endpoint (delayed healing) is after 17-19 weeks postoperatively, the 2nd study endpoint (pseudarthrosis) after 34-36 weeks. The validation of the biomarker will take place in a blinded procedure, whereby the predefined threshold value of the preoperative CD8+ TEMRA cell expression will be compared with the patient's healing status.

Inclusion criteria

• male or female subjects
• subjects > 18 to 80 years of age at the time of screening
• closed fractures
• fractures of the humerus-shaft, forearm-shaft, femur and tibia
• Subjects suffering monotrauma or comparable with monotrauma, due to comparable post-surgery mobilisation
• osteosynthesis
• subject has signed an informed consent form
• legal capacity

Exclusion criteria

• cancer related fractures
• periprosthetic fractures
• known active Hepatitis B virus or Hepatitis C virus infection at screening
• known human immunodeficiency virus (HIV) infection, severe uncontrolled inflammatory disease or severe uncontrolled autoimmune disease (e.g., ulcerative colitis, Crohn's disease
• active malignancy or history of malignancy within 5 years prior to screening
• known diagnosis of moderate to severe dementia based on subject's medical history or severe psychiatric disorder
• known history of drug or alcohol abuse in the past 12 months, based on self-report or medical record
• history of autologous/allogeneic bone marrow (BM) or solid organ transplantation
• exposure to allogeneic cell-based therapy in the past or exposure to autologous cell therapy in the last 12 months before screening
• pregnancy
• subject is currently enrolled in an investigational device or drug trial, or has not yet completed a period of at least 30 days since ending other investigational device or drug trial(s).
• subject is detained or institutionalized under a court order or administrative order
• in the opinion of the investigator, the subject is unsuitable for participating in the study (patient compliance).