Phase II Study of the Effects of rhPDGF-BB Injection on Lateral Epicondylitis

A Phase II Randomized, Single Ascending Dose, Double-blinded, Placebo Controlled, Multi-center Study of the Effects of rhPDGF-BB Injection on Lateral Epicondylitis

The purpose of this study is to determine whether recombinant human platelet-derived growth factor (rhPDGF-BB) Injection is effective in the treatment of lateral epicondylitis (tennis elbow).

Study Overview

• Status: Completed
• Conditions: Lateral Epicondylitis
• Intervention / Treatment: Drug: Placebo; Drug: rhPDGF-BB Injection

Detailed Description

Methodology: Randomized, single ascending dose, double-blinded, placebo controlled, multi-center study

Study Center(s): 6

Number of Subjects: 100

Diagnosis and Main Inclusion Criteria: Lateral epicondylitis; male and female subjects 21 -80 years of age

Study Drug, Dose, Regimen:

Dose A: sodium acetate buffer alone - placebo control Dose B: sodium acetate buffer + 0.45 mg rhPDGF-BB Dose C: sodium acetate buffer + 0.75 mg rhPDGF-BB Dose D: sodium acetate buffer + 1.5 mg rhPDGF-BB Dose E: sodium acetate buffer + 3.0 mg rhPDGF-BB

Duration and Route of Administration: Single administration dose by injection into the extensor carpi radialis brevis (ECRB)

Duration of Follow-up: 24 weeks (6 months) post-operative follow-up

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
    • Tucson, Arizona, United States, 85712
      • Tucson Orthopaedic Institute
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Clinic
  • Florida
    • Bradenton, Florida, United States, 34209
      • Coastal Orthopedics & Sports Medicine
    • Tampa, Florida, United States, 33637
      • Foundation for Orthopaedic Research and Education
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • OrthoCarolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has signed the Institutional Review Board (IRB) approved Informed Consent Form specific to this study prior to enrollment
2. Subject has a clinical diagnosis of lateral epicondylitis
3. Subject's symptoms can be reproduced with resisted supination or wrist dorsiflexion

4. Subject's symptoms have persisted for at least 3 months despite conservative treatment that includes one or combinations of:

   1. Physical therapy
   2. Splinting
   3. Nonsteroidal antiinflammatory drug (NSAID)
   4. Corticosteroid injection
5. Subject is independent, ambulatory, and can comply with all post-injection evaluations and visits
6. Subject is 21-80 years of age and considered to be skeletally mature

Exclusion Criteria:

1. Subject has undergone previous corticosteroid injection therapy to the effected elbow in less than three months prior to enrollment
2. Subject has received previous Platelet Rich Plasma (PRP) injection to the affected elbow
3. Subject is deemed to require a corticosteroid injection into the affected elbow during the course of the study
4. Subject uses chronic medications known to affect the skeleton (e.g. glucocorticoid usage >10mg/day)
5. Subject has undergone surgical intervention to the affected elbow for the treatment of lateral epicondylitis

6. Subject has a positive medical history of any of the following:

   1. medial epicondylitis
   2. radial tunnel syndrome
   3. carpal tunnel syndrome
   4. septic or gouty arthritis
   5. cervical radiculopathy
   6. trauma to the affected elbow within the past 6 weeks
   7. neuromuscular or musculoskeletal deficiency, which limits the ability to perform functional measurement (e.g. grip strength test)
7. Subject currently has an acute infection at the injection site
8. Subject has tested positive or been treated for a malignancy in the past or is suspected of having a malignancy or are currently undergoing radio- or chemotherapy treatment for a malignancy anywhere in the body, whether adjacent to or distant from the proposed rhPDGF-BB Injection treatment site
9. Subject is physically or mentally compromised (e.g. currently being treated for a psychiatric disorder, senile dementia, Alzheimer's disease, etc.) to the extent that the Investigator judges the subject to be unable or unlikely to remain compliant
10. Subject has an allergy to yeast-derived products
11. Subject has received an investigational therapy or approved therapy for investigational use within 30 days of injection procedure or during the follow-up phase of this study
12. Subject is a prisoner, or is known or suspected to be transient
13. Subject's condition represents a worker's compensation case
14. Subject is currently involved in a health-related litigation procedure
15. Subject has documented evidence of a history (e.g. liver testing) of drug/alcohol abuse within the 12 months prior to screening for study entry
16. Subject is pregnant, or able to become pregnant but not practicing a medically-accepted form of birth control, and/or intending to become pregnant during this study period

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Control; Dose A - sodium acetate buffer (0 mg rhPDGF-BB)	Drug: Placebo; sodium acetate buffer (0 mg rhPDGF-BB)
Experimental: 0.45 mg rhPDGF-BB; Dose B - sodium acetate buffer + 0.45 mg rhPDGF-BB	Drug: rhPDGF-BB Injection; Comparison of placebo control (0 mg rhPDGF-BB) and different dosages (0.45, 0.75, 1.5, and 3.0 mg) of rhPDGF-BB Injection administered through a one-time injection
Experimental: 0.75 mg rhPDGF-BB; Dose C - sodium acetate buffer + 0.75 mg rhPDGF-BB	Drug: rhPDGF-BB Injection; Comparison of placebo control (0 mg rhPDGF-BB) and different dosages (0.45, 0.75, 1.5, and 3.0 mg) of rhPDGF-BB Injection administered through a one-time injection
Experimental: 1.5 mg rhPDGF-BB; Dose D - sodium acetate buffer + 1.5 mg rhPDGF-BB	Drug: rhPDGF-BB Injection; Comparison of placebo control (0 mg rhPDGF-BB) and different dosages (0.45, 0.75, 1.5, and 3.0 mg) of rhPDGF-BB Injection administered through a one-time injection
Experimental: 3.0 mg rhPDGF-BB; Dose E - sodium acetate buffer + 3.0 mg rhPDGF-BB	Drug: rhPDGF-BB Injection; Comparison of placebo control (0 mg rhPDGF-BB) and different dosages (0.45, 0.75, 1.5, and 3.0 mg) of rhPDGF-BB Injection administered through a one-time injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Elbow Pain Assessments (VAS), Treated Subjects	Subjects were asked to report current pain level at the fusion site on a 100 mm Visual Analog Scale (with 0 being no pain and 100 being worst pain imaginable).	Baseline, 2, 4, 8, 12, and 24 weeks
Disabilities of the Arm, Shoulder and Hand (DASH), Treated Subjects	The disabilities of the arm, shoulder and hand (DASH) questionnaire is a self-administered region-specific outcome instrument developed as a measure of self-rated upper-extremity disability and symptoms. The DASH consists mainly of a 30-item disability/symptom scale, scored 0 (no disability) to 100.	Baseline, 4, 8, 12, and 24 weeks
Total Score Patient Rated Tennis Elbow Evaluation (PRTEE), All Treated Subjects	The Pain and disability measured by the Patient Rated Tennis Elbow Evaluation (PRTEE) is a 15-item questionnaire designed to measure forearm pain and disability in patients with lateral epicondylitis (also known as "tennis elbow"). The PRTEE allows patients to rate their levels of tennis elbow pain and disability from 0 to 10, and consists of 2 subscales: PAIN subscale (0 = no pain, 10 = worst imaginable)-Pain - 5 items; FUNCTION subscale (0 = no difficulty, 10 = unable to do)Specific activities - 6 itemsUsual activities - 4 items In addition to the individual subscale scores, a total score can be computed on a scale of 100 (0 = no disability), where pain and functional problems are weighted equally	Baseline, 4, 8, 12, and 24 weeks
Grip Strength Test, All Treated Subjects	Grip strength testing will be performed to evaluate changes in the strength and sincerity of effort as a result of treatment for lateral epicondylitis. Testing will be performed to assess the pain-free grip strength (performing the test until discomfort is felt) and maximum grip strength (performing the test to the maximum of their ability). The test will be performed while the patient is standing with the elbow in full extension, as this position has been used to assess grip strength in patients with lateral epicondylitis. A Jamar Plus+ Digital Hand Dynamometer with the grip in the second position will be used because the second position has been assumed to be the most reliable and consistent position. Patients will be asked to perform three repetitions of each test (pain-free and maximum) at each study interval and the mean score will be calculated and used for analysis.	Baseline, 4, 8, 12, and 24 weeks
Maximum Grip Strength, Treated Subjects	A higher grip strength score indicates an improvement. A positive change from baseline indicates an improvement. Grip strength testing will be performed to evaluate changes in the strength and sincerity of effort as a result of treatment for lateral epicondylitis. Testing will be performed to assess the pain-free grip strength (performing the test until discomfort is felt) and maximum grip strength (performing the test to the maximum of their ability). The test will be performed while the patient is standing with the elbow in full extension, as this position has been used to assess grip strength in patients with lateral epicondylitis. A Jamar Plus+ Digital Hand Dynamometer with the grip in the second position will be used because the second position has been assumed to be the most reliable and consistent position. Patients will be asked to perform three repetitions of each test (pain-free and maximum) at each study interval and the mean score will be calculated and used for analysis.	Baseline, 4, 8, 12, and 24 weeks

Collaborators and Investigators

• Sponsor: BioMimetic Therapeutics
• Investigators: Principal Investigator: Edward Akelman, MD, Brown University

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2012
• Primary Completion (Actual): October 21, 2014
• Study Completion (Actual): October 21, 2014

Study Registration Dates

• First Submitted: December 7, 2012
• First Submitted That Met QC Criteria: December 10, 2012
• First Posted (Estimate): December 11, 2012

Study Record Updates

• Last Update Posted (Actual): July 2, 2019
• Last Update Submitted That Met QC Criteria: June 12, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: elbow
• Additional Relevant MeSH Terms: Wounds and Injuries; Musculoskeletal Diseases; Muscular Diseases; Tendon Injuries; Tendinopathy; Arm Injuries; Elbow Tendinopathy; Tennis Elbow; Physiological Effects of Drugs; Angiogenesis Modulating Agents; Growth Substances; Anticoagulants; Angiogenesis Inducing Agents; Becaplermin
• Other Study ID Numbers: BMTI-2010-02