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

NCT ID: NCT03451916

Last Updated: 2023-09-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-26
• Study Completion Date: 2023-09-06

Brief Summary

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.

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.

Conditions

Hip Fracture

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

PLX-PAD

Intervention Type: DRUG

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

Arm 2 Placebo (120 subjects): Placebo (solution comprised of 10% DMSO \[v/v\], 5% HSA \[w/v\], and PlasmaLyte, without cells).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Arm 2 Placebo (120 subjects): Placebo (solution comprised of 10% DMSO \[v/v\], 5% HSA \[w/v\], and PlasmaLyte, without cells).

Interventions

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

Intervention Type: DRUG

Placebo

Arm 2 Placebo (120 subjects): Placebo (solution comprised of 10% DMSO \[v/v\], 5% HSA \[w/v\], and PlasmaLyte, without cells).

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pluristem Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Of California Davis,4860 Y Street

Sacramento, California, United States

Denver Metro Orthopedics, P.C. 499 E. Hampden Avenue, Suite 140 Englewood, CO 80113

Denver, Colorado, United States

ANTRIA, INC,300 Indian Springs Road,Indiana

Indiana, Pennsylvania, United States

MHAT "Ljulin" Department of Orthopedy and Traumatology

Sofia, , Bulgaria

MHAT "Serdika" Department of Orthopedy and Traumatology

Sofia, , Bulgaria

Military Medical Academy

Sofia, , Bulgaria

Specialized Hospital for Active Treatment in Orthopedy

Sofia, , Bulgaria

Charite - Campus Mitte,Campus Virchow-Klinikum

Berlin, , Germany

Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden

Dresden, , Germany

Universitaetsklinikum Muenster

Münster, , Germany

Carmel Medical Center,7 Michal St

Haifa, , Israel

Shaare Zedek Medical Center,The Orthopedic Department,Shmu'el Bait St. 12

Jerusalem, , Israel

Meir Medical Center-Internal Medicine E;59 Tshernichovsky Street

Kfar Saba, , Israel

The Chaim Sheba Medical Center,Tel Hashomer

Ramat Gan, , Israel

Kaplan Medical Center,Pasternak St., P.O.B 1,Rehovot

Rehovot, , Israel

Sourasky Medical Center,6 Weizmann St; Harrison Building 6 Floor

Tel Aviv, , Israel

John Radcliffe Hospital

Oxford, , United Kingdom

Countries

United States; Bulgaria; Germany; Israel; United Kingdom

Other Identifiers

PLX-HF-01

Identifier Type: -

Identifier Source: org_study_id