First in Human study of a microRNA29a mimic (TenoMiR) in patients with lateral elbow tendinopathy - a Randomised, Placebo Controlled Phase 1 trial.

Tendinopathy, encompassing multifactorial tendon disorders characterised by pain and functional limitation, remains a significant burden in musculoskeletal medicine. Here we report a prospective, randomised, double-blind, placebo-controlled Phase 1b first in patient trial of three single ascending doses of intratendinous injection of TenoMiR, a chemically synthesised mimic of microRNA-29a versus placebo conducted in 24 subjects with active lateral elbow tendinopathy (NCT04670289). The primary objective of the study was to determine the safety and tolerability of single ascending doses of TenoMiR in subjects with lateral epicondylitis, with patient reported measures and imaging parameters as secondary outcomes. TenoMiR treatment at 200, 500 or 1500 {micro}g/mL was associated with acceptable safety and tolerability with the geometric mean maximum observed value (Cmax,relative expression compared to control) of miR29a was 3.16, 6.63 and 2.37 respectively. There were no significant treatment- or dose-related trends in clinical laboratory evaluations, vital signs or ECG parameters. Treatment with TenoMiR led to a substantial improvement in tendon structure at all doses over a 90 day period and there was improvement of symptoms and function in both groups. This data supports the mechanism of miRNA-mediated modulation of the early pathophysiologic events that facilitate tissue remodelling in human tendon disease, and provides strong proof of principle that a locally delivered miR29a therapy improves early tendon healing.