Safety and Efficacy of IM Injections of PLX-PAD for the Regeneration of Injured Gluteal Musculature After Total Hip Arthroplasty

Study Overview
=================
Brief Summary
-----------------
Local administration of PLX-PAD single dose, intra-muscular injection for the regeneration of injured gluteal musculature after Total Hip Arthroplasty (THA).

Detailed Description
-----------------
One of the main problems when performing THA via the standard transgluteal approach is the necessary injury of the gluteus medius muscle. The consecutive decrease of contractile muscle substance and the substitution by scar tissue leads to functional deficits of the pelvic-stabilizing musculature with an insufficiency limp in a large number of patients. In the long run the lack of musculature leads to a decrease in bone substance at the insertion sites of the gluteal muscles of the proximal femur. The present study has the aim of establishing a new therapy for iatrogenic gluteal muscle damage. The hypothesis of the present proposal is that intra-muscular (IM) injection of PLX-PAD into the iatrogenically injured gluteus medius muscle after THA results in an improved regeneration of the skeletal muscle tissue and consecutively in an improved functional outcome. Subjects will be assigned to receive one of the two targeted doses of PLX-PAD or placebo. On the treatment day, after suturing the gluteus medius muscle PLX-PAD or placebo will be applied directly to the site of laceration. Patients will be followed up for efficacy assessment up to week 26 and for safety assessment (Adverse events, vital signs, ECG, routinf lab and immunological testing) up to week 52 after THA. Patients will be phoned at week 104 in order to inquire about the occurence of new cancer.

Official Title
-----------------
A Phase I/II, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Intramuscular Injections of Allogeneic PLX-PAD Cells for the Regeneration of Injured Gluteal Musculature After Total Hip Arthroplasty

Conditions
-----------------
Total Hip Arthroplasty, Muscle Injury

Intervention / Treatment
-----------------
* Biological: 150M PLX-PAD
* Biological: 300M PLX-PAD
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects between 50 to 75 years of age Scheduled THA ASA Score ≤ 3 Signed written informed consent Exclusion Criteria: Muscle diseases Severe neurological diseases Opioid long term medication Pain chronification > stadium II of Gerbershagen Immunosuppression due to illness or medication Ankylosing spondylitis History of ectopic bone formation of any localisation Exclusion criteria for MRI (pace maker, defibrillator, ferromagnetic intracerebral clips) Uncontrolled hypertension (defined as diastolic blood pressure > 100 mmHg or systolic blood pressure > 200 mmHg during screening) Life-threatening ventricular arrhythmia or unstable angina - characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged ST segment elevation myocardial infarction and/or TIA/CVA within three (3) months prior to enrollment. Subjects with severe congestive heart failure symptoms (i.e. NYHA Stage IV) Subject has malignancy undergoing treatment including chemotherapy, radiotherapy or immunotherapy Body Mass Index (BMI) of 35 Kg/m2 or greater Known allergies to protein products (horse or bovine serum, or porcine trypsin) used in the cell production process Known HIV, syphilis at time of screening Known active Hepatitis B, or Hepatitis C infection at the time of screening Pregnant or breast-feeding women or women of childbearing potential not protected by an effective contraceptive method of birth control (defined as pearl index < 1) In the opinion of the investigator, the subject is unsuitable for cellular therapy Subject is currently enrolled in, or has not yet completed a period of at least 30 days since ending other investigational device or drug trial(s) Subjects who are legally detained in an official institute

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 75 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 |
| --- | --- |
| Experimental: 150M PLX-PAD<br>Single course, multiple IM injections | Biological: 150M PLX-PAD<br>* Single course, multiple IM injections<br>|
| Experimental: 300M PLX-PAD<br>Single course, multiple IM injections | Biological: 300M PLX-PAD<br>* Single course, multiple IM injections<br>|
| Placebo Comparator: Placebo<br>Single course, multiple IM injections | Biological: Placebo<br>* Single course, multiple IM injections<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Day 0 to Week 26 in the Maximal Voluntary Isometric Contraction (MVIC) Moment of the Injured Side to Assess Gluteus Medius Strength. | Change from Visit 2 (Day 0) to Week 26 in the maximal voluntary isometric contraction (MVIC) moment of the injured side as measured by isometric dynamometry to assess Gluteus Medius force strength. | Day 0 to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Day 0 to Week 26 in Muscle Volume. | Change from Visit 2 (Day 0) to Week 26 in Muscle Volume as Measured by MRI. | Day 0 to Week 26 | 
| Change From Day 1 to Week 12 in Mean Fiber Diameter. | Change from Visit 3 (Day 1) to Week 12 in Mean Fiber Diameter as Measured by Muscle Biopsy. | Day 1 to Week 12 | 
| Change From Day 0 to Week 26 in the Ratio of Injured to Contralateral Pelvic Shift . | Change from Visit 2 (Day 0) to Week 26 in the Ratio of Injured to Contralateral Pelvic Shift as Measured by Gait Analysis | Day 0 to Week 26 | 
| Change From Day 0 to Week 26 in the Visual Analog Scale (VAS) Pain Score. | Visual Analog Scale (VAS) Pain Score ranges from 0 mm (no pain) to 100 mm (worse possible pain) | Day 0 to Week 26 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
THA, Muscle injury