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 µg/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.

NLM has received consultation fees or speaker honoraria from AbbVie, Causeway Therapeutics, Novartis and Stryker. IBM has received research grants, consultation fees or speaker honoraria from AbbVie, Amgen, BMS, Celgene, Causeway Therapeutics, Evelo, Janssen, Lilly, Moonlake, Novartis, Pfizer and UCB. DSG, ID, DB and NLM are employees of Causeway Therapeutics and, as such, may be eligible for Causeway stock and stock options. AK and Pui Man Leung have no competing interests.

NCT04670289

https://clinicaltrials.gov/study/NCT04670289?intr=TenoMiR&rank=1

This study was funded by Causeway Therapeutics; clinicaltrials.org NCT04670289.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted according to the ethical principles of the Declaration of Helsinki and approved by the Wales REC1 (Health and Care Research Wales) Research Ethics Committee (REC 9/WA/0300) The study is registered with ClinicalTrials.gov (NCT04670289).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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All data produced in the present study are available upon reasonable request to the authors.