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

• ClinicalTrials.gov Identifier: NCT04670289
• Recruitment Status: Completed
• First Posted: December 17, 2020
• Last Update Posted: September 17, 2021
• Sponsor: Causeway Therapeutics
• Information provided by (Responsible Party): Causeway Therapeutics

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Tennis Elbow	Drug: TenoMiR (Low Dose); Drug: TenoMiR (Medium Dose); Drug: TenoMiR (High Dose); Drug: Placebo	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Prospective, Controlled, Randomised, Double Blind, Single Centre Trial
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 14, 2020
• Actual Primary Completion Date: May 19, 2021
• Actual Study Completion Date: August 18, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events (AEs) as assessed by comparison of clinical laboratory abnormalities between TenoMiR versus placebo. [ Time Frame: 14 days ]
   Comparison of clinical laboratory abnormalities between TenoMiR versus placebo as measured by blood chemistry, haematology, coagulation, serology and urinalysis.
2. Incidence of Treatment-Emergent Adverse Events (AEs) as assessed by comparison of changes in vital signs between TenoMiR versus placebo. [ Time Frame: 14 days ]
   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.
3. Incidence of Treatment-Emergent Adverse Events (AEs) as assessed by comparison of changes in 12 lead ECG parameters between TenoMiR versus placebo. [ Time Frame: 14 days ]
   Comparison of changes in 12 lead ECG parameters as measured by Heart Rate and PR, RR, QRS, QT and QT intervals.
4. Incidence of Treatment-Emergent Adverse Events (AEs) as assessed by comparison of physical examination between TenoMiR versus placebo. [ Time Frame: 14 days ]
   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.
5. Incidence of Treatment-Emergent Adverse Events (AEs) as assessed by comparison of skin score assessment between TenoMiR versus placebo. [ Time Frame: 14 days ]
   Comparison of changes in skin score assessment of injection site between TenoMiR versus placebo as measured by for erythema, pain, tenderness and swelling.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United Kingdom

MAC Clinical Research

Manchester, United Kingdom

Sponsors and Collaborators

Causeway Therapeutics

More Information

• Responsible Party: Causeway Therapeutics
• ClinicalTrials.gov Identifier: NCT04670289
• Other Study ID Numbers: CWT-TE1
• First Posted: December 17, 2020
• Last Update Posted: September 17, 2021
• Last Verified: September 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Tennis Elbow; Elbow Tendinopathy; Tendinopathy; Muscular Diseases; Musculoskeletal Diseases; Arm Injuries; Wounds and Injuries; Tendon Injuries