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

• ClinicalTrials.gov Identifier: NCT01525667
• Recruitment Status: Completed
• First Posted: February 3, 2012
• Results First Posted: February 23, 2015
• Last Update Posted: September 21, 2015
• Sponsor: Pluristem Ltd.
• Information provided by (Responsible Party): Pluristem Ltd.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Total Hip Arthroplasty; Muscle Injury	Biological: 150M PLX-PAD; Biological: 300M PLX-PAD; Biological: Placebo	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Study Start Date: November 2012
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: June 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: 150M PLX-PAD; Single course, multiple IM injections	Biological: 150M PLX-PAD; Single course, multiple IM injections
Experimental: 300M PLX-PAD; Single course, multiple IM injections	Biological: 300M PLX-PAD; Single course, multiple IM injections
Placebo Comparator: Placebo; Single course, multiple IM injections	Biological: Placebo; Single course, multiple IM injections

Outcome Measures

Primary Outcome Measures :

1. Change From Day 0 to Week 26 in the Maximal Voluntary Isometric Contraction (MVIC) Moment of the Injured Side to Assess Gluteus Medius Strength. [ Time Frame: Day 0 to Week 26 ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female subjects between 50 to 75 years of age
2. Scheduled THA
3. ASA Score ≤ 3
4. Signed written informed consent

Exclusion Criteria:

1. Muscle diseases
2. Severe neurological diseases
3. Opioid long term medication
4. Pain chronification > stadium II of Gerbershagen
5. Immunosuppression due to illness or medication
6. Ankylosing spondylitis
7. History of ectopic bone formation of any localisation
8. Exclusion criteria for MRI (pace maker, defibrillator, ferromagnetic intracerebral clips)
9. Uncontrolled hypertension (defined as diastolic blood pressure > 100 mmHg or systolic blood pressure > 200 mmHg during screening)
10. Life-threatening ventricular arrhythmia or unstable angina - characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged
11. 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)
12. Subject has malignancy undergoing treatment including chemotherapy, radiotherapy or immunotherapy
13. Body Mass Index (BMI) of 35 Kg/m2 or greater
14. Known allergies to protein products (horse or bovine serum, or porcine trypsin) used in the cell production process
15. Known HIV, syphilis at time of screening
16. Known active Hepatitis B, or Hepatitis C infection at the time of screening
17. 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)
18. In the opinion of the investigator, the subject is unsuitable for cellular therapy
19. 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)
20. Subjects who are legally detained in an official institute

Contacts and Locations

Locations

Germany

Charité Universitätsmedizin Berlin

Berlin, Germany, 10117

Sponsors and Collaborators

Pluristem Ltd.

Investigators

• Principal Investigator: Carsten Perka, MD; Charité Universitätsmedizin Berlin, Dept. Of Orthopedic Surgery, Charitéplatz 1, 10117 Berlin, Germany

More Information

• Responsible Party: Pluristem Ltd.
• ClinicalTrials.gov Identifier: NCT01525667
• Other Study ID Numbers: PLX-PAD 1301-01
• First Posted: February 3, 2012
• Results First Posted: February 23, 2015
• Last Update Posted: September 21, 2015
• Last Verified: January 2015

Keywords provided by Pluristem Ltd.:

THA; Muscle injury