Clinical trial NCT03451916: Treatment of Muscle Injury Following Arthroplasty for Hip Fracture (HF)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hip Fracture
Lead sponsor: Pluristem Ltd.
Sponsor class: INDUSTRY
First posted: 2018-03-02
Enrollment: 240
Sex: ALL
Minimum age (years): 0
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: , subjects will be randomized using a 1:1 allocation scheme to either 150×10\^6 PLX-PAD cells or to placebo treatment, respectively
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Short Physical Performance Battery (SPPB) score
timeFrame: Week 26.
Secondary outcomes:
measure: Hip abduction strength of the injured leg
timeFrame: Week 26.
measure: Change from baseline to Week 52 in lower extremity measure (LEM) (retrospective collection of pre-fracture LEM at Day 5±1).
timeFrame: baseline to Week 52
measure: SPPB score
timeFrame: Week 52.
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University Of California Davis,4860 Y Street
state: California
city: Denver
country: United States
facility: Denver Metro Orthopedics, P.C. 499 E. Hampden Avenue, Suite 140 Englewood, CO 80113
state: Colorado
city: Indiana
country: United States
facility: ANTRIA, INC,300 Indian Springs Road,Indiana
state: Pennsylvania
city: Sofia
country: Bulgaria
facility: MHAT "Ljulin" Department of Orthopedy and Traumatology
city: Sofia
country: Bulgaria
facility: MHAT "Serdika" Department of Orthopedy and Traumatology
city: Sofia
country: Bulgaria
facility: Military Medical Academy
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment in Orthopedy
city: Berlin
country: Germany
facility: Charite - Campus Mitte,Campus Virchow-Klinikum
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden
city: Münster
country: Germany
facility: Universitaetsklinikum Muenster
city: Haifa
country: Israel
facility: Carmel Medical Center,7 Michal St
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center,The Orthopedic Department,Shmu'el Bait St. 12
city: Kfar-Saba
country: Israel
facility: Meir Medical Center-Internal Medicine E;59 Tshernichovsky Street
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center,Tel Hashomer
city: Reẖovot
country: Israel
facility: Kaplan Medical Center,Pasternak St., P.O.B 1,Rehovot
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center,6 Weizmann St; Harrison Building 6 Floor
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
Study officials:
References: