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

Study Overview
=================
Brief Summary
-----------------
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).

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

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

Conditions
-----------------
Lateral Epicondylitis

Intervention / Treatment
-----------------
* Drug: rhPDGF-BB Injection
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject has signed the Institutional Review Board (IRB) approved Informed Consent Form specific to this study prior to enrollment Subject has a clinical diagnosis of lateral epicondylitis Subject's symptoms can be reproduced with resisted supination or wrist dorsiflexion Subject's symptoms have persisted for at least 3 months despite conservative treatment that includes one or combinations of: Physical therapy Splinting Nonsteroidal antiinflammatory drug (NSAID) Corticosteroid injection Subject is independent, ambulatory, and can comply with all post-injection evaluations and visits Subject is 21-80 years of age and considered to be skeletally mature Exclusion Criteria: Subject has undergone previous corticosteroid injection therapy to the effected elbow in less than three months prior to enrollment Subject has received previous Platelet Rich Plasma (PRP) injection to the affected elbow Subject is deemed to require a corticosteroid injection into the affected elbow during the course of the study Subject uses chronic medications known to affect the skeleton (e.g. glucocorticoid usage >10mg/day) Subject has undergone surgical intervention to the affected elbow for the treatment of lateral epicondylitis Subject has a positive medical history of any of the following: medial epicondylitis radial tunnel syndrome carpal tunnel syndrome septic or gouty arthritis cervical radiculopathy trauma to the affected elbow within the past 6 weeks neuromuscular or musculoskeletal deficiency, which limits the ability to perform functional measurement (e.g. grip strength test) Subject currently has an acute infection at the injection site 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 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 Subject has an allergy to yeast-derived products 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 Subject is a prisoner, or is known or suspected to be transient Subject's condition represents a worker's compensation case Subject is currently involved in a health-related litigation procedure 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 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

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Control<br>Dose A - sodium acetate buffer (0 mg rhPDGF-BB) | Drug: Placebo<br>* sodium acetate buffer (0 mg rhPDGF-BB)<br>|
| Experimental: 0.45 mg rhPDGF-BB<br>Dose B - sodium acetate buffer + 0.45 mg rhPDGF-BB | Drug: rhPDGF-BB Injection<br>* 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<br>|
| Experimental: 0.75 mg rhPDGF-BB<br>Dose C - sodium acetate buffer + 0.75 mg rhPDGF-BB | Drug: rhPDGF-BB Injection<br>* 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<br>|
| Experimental: 1.5 mg rhPDGF-BB<br>Dose D - sodium acetate buffer + 1.5 mg rhPDGF-BB | Drug: rhPDGF-BB Injection<br>* 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<br>|
| Experimental: 3.0 mg rhPDGF-BB<br>Dose E - sodium acetate buffer + 3.0 mg rhPDGF-BB | Drug: rhPDGF-BB Injection<br>* 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<br>|

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 items Usual 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
elbow