In this clinical trial, we evaluated the safety and efficacy of rhBMP6 undergoing HTO. The systemic pharmacokinetics (PK), safety, acceleration of new bone formation, and tolerability were examined.
We assigned 20 HTO patients into this randomized, controlled, blinded Phase I-II clinical trial (EudraCT number 2015-001691-21). RhBMP6 or placebo were implanted into the tibial wedge-defects. Patients were followed for 24 months by clinical examination, x-rays and CT scans. Efficacy outcome was defined as percentage of defect filled with newly formed bone, based on x-ray analyses of day 1, week 6 and 24, month 12, 18 and 24. The bone mineral density (BMD), as well as bone formation in the defect area, was measured on CT scans by ITK-SNAP program transferring voxels into BMD (mgs/cm3) by using a bone 3 CT calibration phantom at weeks 9 and 14 post-surgery.
CT scans from HTO defects of patients treated with rhBMP6/ABC (n=10) showed an accelerated bone healing when compared to placebo treated patients (n=10). BMD gain was higher in the treatment group after 9 and 14 weeks: 47.8 ± 24.1 vs. 22.2 ± 12.3 (P=0.008) and 89.7 ± 29.1 vs. 53.6 ± 21.9 (P=0.006). X-rays from day 1, weeks 6 and 24, and months 12, 18, 24 confirmed the enhanced bone formation in rhBMP6/ABC treated patients. The use of rhBMP6/ABC was not associated with serious adverse events during the entire 24 months follow-up. The availability of rhBMP6 was detected in the plasma of only one out of 10 patients (8.3 mg/ml) from locally administered rhBMP6/ABC implants within the first 15 minutes after implantation. As measured on CT scans, the BMD increased distally from the osteotomy wedge in rhBMP6/ABC treated patients.
rhBMP6/ABC at a dose of 100 µg/ml accelerated the bone formation rate without serious adverse events, with a good tolerability and no systemic distribution.