Novel parathyroid hormone-based bone graft substitute, KUR-111, in treatment of tibial plateau fractures: a prospective, randomised, open-label, multicenter study.

Abstract

The treatment of closed tibial plateau fractures (TPF) is complex and carries a risk of malunion. Parathyroid hormone (PTH) plays a key role in bone metabolism, and a PTH-peptide (PTH_1 - 34) promotes bone healing. The objective was to evaluate the safety and efficacy of a novel PTH-based bone-graft-substitute (KUR-111) in the treatment of TPF. The study was a randomised, controlled, multicenter, open-label (dose-blinded), and dose-finding clinical trial. Subjects were randomised into 3 groups (iliac crest autograft (control); KUR-111-low; and high-dose TGplPTH1-34). The primary efficacy endpoint was the rate of union by computed tomography (CT) at 16weeks, as assessed by the Independent Radiologist Evaluation Panel (IREP). A total of 183 TPF were enrolled and treated. The primary endpoint was met, as statistical non-inferiority was demonstrated for KUR-111-high compared with autograft at 16weeks. KUR-111-high significantly (p = 0.03) increased union rates compared to KUR-111-low (83.6%vs66.1%). IREP and a clinician-assessed composite score of fracture healing showed higher healing rates for KUR-111-high than KUR-111-low or autograft. Loss of reduction was minimal (0.4-0.9 mm) without significant differences (p > 0.10) among groups. Mean pain of the treated knee improved from baseline, with the least pain for KUR-111-high at all timepoints. Clinically significant donor-site pain was reported by 61.8% at discharge and remained in 12.2% of subjects at 104weeks. By 104weeks, analgesic use following KUR-111-high was less than one-half (9.8%vs24.1%), and opioid use was approximately 7-fold lower (1.6%vs12.1%) as compared to autograft. KUR-111-high has the potential to be a promising adjunctive therapy in the treatment of closed TPFs. Therapeutic Level I.