Safety, Tolerability, and Pharmacokinetics of Single Dose TenoMiR as a Treatment for Tennis Elbow

A Phase 1, Single-Centre, Randomised, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability and Pharmacokinetics of Single Ascending Doses of TenoMiR Injections in Subjects With Lateral Epicondylitis

This study is testing a drug called TenoMiR that is being developed for the treatment of tennis elbow (lateral epicondylitis). The study drug is a new compound that works by improving the quality of the collagen which helps repair damage to the elbow. The study drug is being developed in the hope of providing a more reliable treatment than those currently available and can be given at the time of first diagnosis, so that recovery can begin as soon as possible.

Study Overview

• Status: Completed
• Conditions: Tennis Elbow
• Intervention / Treatment: Drug: Placebo; Drug: TenoMiR (Low Dose); Drug: TenoMiR (Medium Dose); Drug: TenoMiR (High Dose)

Detailed Description

TenoMiR a chemically synthesised mimic of microRNA-29a (miR29a) which has improved stability, activity and cellular uptake while being non-immunogenic, has been created to restore miR29a levels back to pre-injury levels.

TenoMiR is unique in directly targeting the key changes in collagen production associated with tendinopathy. Unlike other therapies, TenoMiR has a well-defined mode-of-action that is supported by a wealth of scientific data. Moreover, treatment with TenoMiR does not require invasive biopsies and can be delivered at the point of initial diagnosis initiating recovery at the very earliest time.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom
    • MAC Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has a clinical diagnosis of lateral epicondylitis.
2. Aside from lateral epicondylitis, the subject is otherwise healthy as determined by a responsible physician, based on medical history, physical examinations, concomitant medication, vital signs, 12-lead ECGs and clinical laboratory evaluations. Laboratory values may be re-tested once at the discretion of the Investigator.
3. Subject's symptoms can be reproduced with resisted supination or wrist dorsiflexion (as confirmed by tenderness at lateral epicondyle and positive pick up back of chair sign).

4. Subject's symptoms have persisted for at least 6 weeks to 6 months, despite conservative treatment that includes 1 or combinations of:

   1. Physical therapy
   2. Splinting
   3. NSAIDs

Exclusion Criteria:

Subjects with any of the following will be excluded from study participation:

1. Subject has undergone previous corticosteroid injection therapy to the affected elbow in less than 6 months prior to enrolment.
2. Subjects unwilling or unable to discontinue use of pain medication (opiate or NSAID) from at least 1 week prior to Investigational Medicinal Product (IMP) administration.
3. Subject has received previous Platelet-Rich Plasma (PRP) injection to the affected elbow.
4. Subject uses or has recent use of medications known to affect the skeleton (e.g., glucocorticoid usage >5 mg/day, fluoroquinolone antibiotics).
5. Subject has undergone surgical intervention to the affected elbow for the treatment of lateral epicondylitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; TenoMiR intralesional injection	Drug: TenoMiR (Low Dose); Mimic of miR29a; Other Names: CWT-001; Drug: TenoMiR (Medium Dose); Mimic of miR29a; Other Names: CWT-001; Drug: TenoMiR (High Dose); Mimic of miR29a; Other Names: CWT-001
Placebo Comparator: Placebo; 0.9% saline intralesional injection	Drug: Placebo; 0.9% saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events (AEs) as assessed by comparison of clinical laboratory abnormalities between TenoMiR versus placebo.	Comparison of clinical laboratory abnormalities between TenoMiR versus placebo as measured by blood chemistry, haematology, coagulation, serology and urinalysis.	14 days
Incidence of Treatment-Emergent Adverse Events (AEs) as assessed by comparison of changes in vital signs between TenoMiR versus placebo.	Comparison of changes in vital signs between TenoMiR versus placebo as measured by supine vital signs including pulse rate, blood pressure, respiration rate and oral temperature.	14 days
Incidence of Treatment-Emergent Adverse Events (AEs) as assessed by comparison of changes in 12 lead ECG parameters between TenoMiR versus placebo.	Comparison of changes in 12 lead ECG parameters as measured by Heart Rate and PR, RR, QRS, QT and QT intervals.	14 days
Incidence of Treatment-Emergent Adverse Events (AEs) as assessed by comparison of physical examination between TenoMiR versus placebo.	Comparison of changes in physical examination between TenoMiR versus placebo as measured by height, BMI, and body weight, and assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular system, abdomen (liver and spleen), lymph nodes and extremities.	14 days
Incidence of Treatment-Emergent Adverse Events (AEs) as assessed by comparison of skin score assessment between TenoMiR versus placebo.	Comparison of changes in skin score assessment of injection site between TenoMiR versus placebo as measured by for erythema, pain, tenderness and swelling.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single dose pharmacokinetics (PK) of TenoMiR administration in subjects with lateral epicondylitis (Cmax).	Plasma PK by maximum drug plasma concentration (Cmax).	90 days
Single dose pharmacokinetics (PK) of TenoMiR administration in subjects with lateral epicondylitis (tmax).	Plasma PK by time to reach Cmax (tmax).	90 days
Single dose pharmacokinetics (PK) of TenoMiR administration in subjects with lateral epicondylitis (AUC).	Plasma PK by area under the plasma vs. concentration time curve (AUC).	90 days
Visual Analogue Score (VAS) pain score	Changes in pain score per group	90 days
Disabilities of the Arm, Shoulder, and Hand (Quick DASH) score	Changes in Quick DASH per group	90 days
American Shoulder and Elbow Surgeons Elbow (ASES-E) score	Changes in ASES-E per group	90 days
Patient Rated Tennis Elbow Evaluation (PRTEE) score	Changes in PRTEE per group	90 days
Ultrasound assessment	Change in analysis of focal hypoechoic areas within the tendon per group	90 days

Collaborators and Investigators

• Sponsor: Causeway Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2020
• Primary Completion (Actual): May 19, 2021
• Study Completion (Actual): August 18, 2021

Study Registration Dates

• First Submitted: November 26, 2020
• First Submitted That Met QC Criteria: December 15, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): September 17, 2021
• Last Update Submitted That Met QC Criteria: September 16, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Musculoskeletal Diseases; Muscular Diseases; Tendon Injuries; Tendinopathy; Arm Injuries; Elbow Tendinopathy; Tennis Elbow
• Other Study ID Numbers: CWT-TE1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No