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

Tracking Information

• First Submitted Date: November 26, 2020
• First Posted Date: December 17, 2020
• Last Update Posted Date: September 17, 2021
• Actual Study Start Date: August 14, 2020
• Actual Primary Completion Date: May 19, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 15, 2020)

• 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.
• 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.
• 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.
• 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.
• 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 15, 2020)

• 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).
• 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).
• 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).
• Visual Analogue Score (VAS) pain score [ Time Frame: 90 days ]
  Changes in pain score per group
• Disabilities of the Arm, Shoulder, and Hand (Quick DASH) score [ Time Frame: 90 days ]
  Changes in Quick DASH per group
• American Shoulder and Elbow Surgeons Elbow (ASES-E) score [ Time Frame: 90 days ]
  Changes in ASES-E per group
• Patient Rated Tennis Elbow Evaluation (PRTEE) score [ Time Frame: 90 days ]
  Changes in PRTEE per group
• Ultrasound assessment [ Time Frame: 90 days ]
  Change in analysis of focal hypoechoic areas within the tendon per group

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability, and Pharmacokinetics of Single Dose TenoMiR as a Treatment for Tennis Elbow
• 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
• 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.

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
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Prospective, Controlled, Randomised, Double Blind, Single Centre Trial

Masking: Double (Participant, Investigator)
Primary Purpose: Treatment

• Condition: Tennis Elbow

Intervention

• 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
• Drug: Placebo
  0.9% saline

Study Arms

• Experimental: Treatment
  TenoMiR intralesional injection
  Interventions:

  • Drug: TenoMiR (Low Dose)
  • Drug: TenoMiR (Medium Dose)
  • Drug: TenoMiR (High Dose)
• Placebo Comparator: Placebo
  0.9% saline intralesional injection
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 15, 2020): 24
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 18, 2021
• Actual Primary Completion Date: May 19, 2021 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT04670289
• Other Study ID Numbers: CWT-TE1
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Causeway Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Causeway Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Causeway Therapeutics
• Verification Date: September 2021