Treatment of Muscle Injury Following Arthroplasty for Hip Fracture (HF)

Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study, Designed to Determine the Efficacy, Safety, and Tolerability of Intramuscular Administration of Allogeneic PLX-PAD Cells for the Treatment of Muscle Injury Following Arthroplasty for Hip Fracture

The objectives of this study are to assess the efficacy, safety, and tolerability of PLX-PAD intramuscular administration for the treatment of muscle injury following arthroplasty for HF.

Study Overview

• Status: Completed
• Conditions: Hip Fracture
• Intervention / Treatment: Drug: PLX-PAD; Drug: Placebo

Detailed Description

This will be a Phase III, multinational, randomized, double-blind, placebo-controlled study, assessing the efficacy, safety, and tolerability of intramuscular (IM) administration of allogeneic PLX-PAD cells for the treatment of muscle injury following arthroplasty for HF as compared to placebo treatment. Both treatment arms will receive standard of care treatment per local practice.

The study will comprise 2 periods:

1. Main study period - from Screening to 52 weeks post-treatment. During this period, the subjects will have the following study visits: Screening, Day 0 (treatment and surgery day), Day 1, Day 5, Week 6, Week 12, Week 26 and Week 52.
2. Safety follow-up period - from Week 52 to Week 104. During this safety follow-up period, there will be a phone call visit at Week 104 and Only survival and quality of life data, serious adverse events (SAEs) and new malignancy adverse events will be collected.

The main study period will comprise 4 periods:

1. Screening and pre-surgery time
2. Surgery and treatment with PLX-PAD or placebo (Day 0)
3. Hospital follow-up until Day 5±1, at least
4. Follow-up period up to 52 weeks following study treatment administration. Subjects will be assessed for study eligibility before the emergency surgery for HF. After being found eligible, subjects will be randomized using a 1:1 allocation scheme to either 150×106 PLX-PAD cells or to placebo treatment, respectively. Within 48 hours of admission and up to 72 hours following fracture, subjects will undergo HA or THA. During the surgical procedure, the subjects will receive the investigational product in accordance with the treatment group to which they were randomized. Thereafter, visits will be conducted at Days 1 and 5±1, and at Weeks 6, 12, 26, 52 and 104.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1606
    • Military Medical Academy
  • Sofia, Bulgaria, 1303
    • MHAT "Ljulin" Department of Orthopedy and Traumatology
  • Sofia, Bulgaria, 1303
    • MHAT "Serdika" Department of Orthopedy and Traumatology
  • Sofia, Bulgaria, 1614
    • Specialized Hospital for Active Treatment in Orthopedy
• Germany
  • Berlin, Germany, 10117
    • Charite - Campus Mitte,Campus Virchow-Klinikum
  • Dresden, Germany, 01307
    • Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden
  • Münster, Germany, 48149
    • Universitaetsklinikum Muenster
• Israel
  • Haifa, Israel, 3436212
    • Carmel Medical Center,7 Michal St
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center,The Orthopedic Department,Shmu'el Bait St. 12
  • Kfar-Saba, Israel, 44281
    • Meir Medical Center-Internal Medicine E;59 Tshernichovsky Street
  • Ramat Gan, Israel, 52621
    • The Chaim Sheba Medical Center,Tel Hashomer
  • Reẖovot, Israel, 76100
    • Kaplan Medical Center,Pasternak St., P.O.B 1,Rehovot
  • Tel Aviv, Israel, 64239
    • Sourasky Medical Center,6 Weizmann St; Harrison Building 6 Floor
• United Kingdom
  • Oxford, United Kingdom, OX3 9DU
    • John Radcliffe Hospital
• United States
  • California
    • Sacramento, California, United States, 95817
      • University Of California Davis,4860 Y Street
  • Colorado
    • Denver, Colorado, United States, 80113
      • Denver Metro Orthopedics, P.C. 499 E. Hampden Avenue, Suite 140 Englewood, CO 80113
  • Pennsylvania
    • Indiana, Pennsylvania, United States, 15701
      • ANTRIA, INC,300 Indian Springs Road,Indiana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 88 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female subjects
2. Subjects up to 90 years of age, inclusive, at the time of Screening
3. Subjects suffering low energy trauma with intracapsular neck of femur fracture.
4. Planned to be treated with total hip arthroplasty (THA) or hemi-arthroplasty (HA) within 48 hours of hospital admission and 72 hours post fracture.
5. Subjects able to walk 10 feet/3 meters before the fracture.
6. Signed an informed consent.

Exclusion Criteria:

• 1. Any significant musculoskeletal, neurologic or neuromuscular disease causing muscle weakness and/or affecting mobility 2. Current fracture is due to bone pathology other than osteoporosis or due to major trauma 3. Planned orthopedic surgery on lower limbs (excluding hip arthroplasty) within the next 12 months.

  4. Diabetes mellitus with HbA1c >10% at Screening. 5. Known current or history of proliferative retinopathy or diabetic retinopathy.

  6. Known active Hepatitis B virus or Hepatitis C virus infection. 7. Known human immunodeficiency virus (HIV) infection, severe uncontrolled inflammatory disease or severe uncontrolled autoimmune disease (e.g., ulcerative colitis, Crohn's disease, etc).

  8. Subjects on renal replacement therapy or with estimated glomerular filtration rate (eGFR) <15 mL/min/1.73m2 9. Severe congestive heart failure symptoms (New York Heart Association [NYHA] Stage IV).

  10. Known uncontrolled severe hypertension. 11. Treatment with anabolic steroids within 6 months prior to study start 12. Active malignancy or history of malignancy within 3 years prior to study start 13. Known moderate to severe dementia or severe psychiatric disorder. 14. Known allergies to any of the following: dimethyl sulfoxide (DMSO), human serum albumin (HSA), bovine serum albumin, PlasmaLyte.

  15. History of allergic/hypersensitivity reaction to any substance having required hospitalization and/or treatment with IV steroids/epinephrine 16. Pulmonary disease requiring supplemental oxygen treatment on a daily basis. 17. life expectancy of less than 6 months, for reasons other than HF complications, 18. 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).

  19. In the opinion of the Investigator, the subject is unsuitable for participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PLX-PAD; • Arm 1 - PLX-PAD (120 subjects): 150×10^6 PLX-PAD cells (10×10^6 cells/mL) in a mixture containing 10% DMSO (v/v), 5% HSA (w/v) and PlasmaLyte.	Drug: PLX-PAD; PLX-PAD (120 subjects): 150×10^6 PLX-PAD cells (10×10^6 cells/mL) in a mixture containing 10% DMSO (v/v), 5% HSA (w/v) and PlasmaLyte
Placebo Comparator: Placebo; Arm 2 Placebo (120 subjects): Placebo (solution comprised of 10% DMSO [v/v], 5% HSA [w/v], and PlasmaLyte, without cells).	Drug: Placebo; Arm 2 Placebo (120 subjects): Placebo (solution comprised of 10% DMSO [v/v], 5% HSA [w/v], and PlasmaLyte, without cells).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Short Physical Performance Battery (SPPB) score	Week 26.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hip abduction strength of the injured leg		Week 26.
Change from baseline to Week 52 in lower extremity measure (LEM) (retrospective collection of pre-fracture LEM at Day 5±1).		baseline to Week 52
SPPB score	The Short Physical Performance Battery (SPPB) is an objective assessment tool for evaluating lower extremities function. The SPPB consists of 3 types of physical maneuvers: balance test, speed gait test, and chair stand test. Results from each maneuvers test are scored on a scale of 0 to 4, with an increasing composite score indicating an improved lower extremities function level. The total maximum score of SPPB is 12.	Week 52.

Collaborators and Investigators

• Sponsor: Pluristem Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2018
• Primary Completion (Actual): April 29, 2022
• Study Completion (Actual): September 6, 2023

Study Registration Dates

• First Submitted: February 25, 2018
• First Submitted That Met QC Criteria: February 25, 2018
• First Posted (Actual): March 2, 2018

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Femoral Fractures; Hip Injuries; Fractures, Bone; Hip Fractures
• Other Study ID Numbers: PLX-HF-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No