E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Muscle Injury Following Arthroplasty for Hip Fracture |
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E.1.1.1 | Medical condition in easily understood language |
Muscle Injury after hip replacement or reconstruction following Hip Fracture |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10028315 |
E.1.2 | Term | Muscle injuries |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objectives of this study are to assess the efficacy, safety and tolerability of PLX-PAD IM administration for the treatment of muscle injury following arthroplasty for hip fracture. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the inclusion criteria listed below to be eligible for the study: 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 THA or HA, via direct lateral approach, within 48 hours of hospital admission and 72 hours post-fracture. 5. Subject able to walk 10 feet/3 meters before the fracture (with or without walking aids and without help of a person most of the time), based on self-report.
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E.4 | Principal exclusion criteria |
Subjects with any 1 of the exclusion criteria listed below will not be eligible for the study: 1. Any significant musculoskeletal (including ectopic bone formation), neurologic or neuromuscular disease causing muscle weakness and/or affecting mobility at the time of Screening, based on the Investigator’s judgment. 2. Current fracture is due to bone pathology other than osteoporosis (as diagnosed on the pre-operative X-ray) or due to major trauma (e.g., car accident). 3. Planned orthopedic surgery on lower limbs (excluding hip arthroplasty) within the next 12 months. 4. Diabetes mellitus with glycosylated hemoglobin (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 at Screening. 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. Immunosuppression due to illness or medication (e.g., high dose corticosteroids, calcineurin inhibitors, anti-tumor necrosis factor (TNF), anti-IL-6, anti-p40, etc; prednisone equivalent lower than 10 mg/day is accepted) at the time of Screening. 9. AST or ALT >3× upper limit of normal (ULN). Subjects with higher levels may be included if the condition associated with the increase in those liver enzymes is known and is considered clinically stable. 10. Subjects on renal replacement therapy or with estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 (based on Modification of Diet in Renal Disease [MDRD] equation). 11. Severe congestive heart failure symptoms (New York Heart Association [NYHA] Stage IV) at Screening. 12. Known uncontrolled severe hypertension. 13. Treatment with anabolic steroids within 6 months prior to Screening. 14. Albumin <2.5 g/dL. 15. Active malignancy or history of malignancy within 3 years prior to Screening with the exception of successfully resected basal cell carcinoma or skin squamous cell carcinoma not located on the injured leg. 16. Known moderate to severe dementia or severe psychiatric disorder. 17. Known allergies to any of the following: DMSO, HSA, bovine serum albumin, and PlasmaLyte. 18. History of allergic/hypersensitivity reaction to any substance having required hospitalization and/or treatment with IV steroids/epinephrine, history of acute transfusion reaction, known allergy to more than 3 allergens, or in the opinion of the Investigator the subject is at high risk of developing severe allergic/hypersensitivity reactions. 19. Known history of severe atopic disease (including but not limited to chronic urticaria, respiratory allergy requiring oral steroids), known history of uncontrolled asthma (Global Initiative for Asthma [GINA] III-IV) 20. Pulmonary disease requiring supplemental oxygen treatment on a daily basis. 21. Known history of drug or alcohol abuse in the past 12 months, based on self-report or medical record. 22. History of autologous/allogeneic BM or solid organ transplantation. 23. Exposure to allogeneic cell-based therapy in the past or exposure to autologous cell therapy in the last 12 months before Screening. 24. Current evidence/sign supporting an assessment of life expectancy of less than 6 months, for reasons other than HF complications, based on the Investigator’s judgment. 25. Subject is currently enrolled in an investigational device or drug trial, or has not yet completed a period of at least 30 days since ending other investigational device or drug trial(s). 26. In the opinion of the Investigator, the subject is unsuitable for participating in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Short Physical Performance Battery (SPPB) score at Week 26. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At weeks 6, 12, 26 and 52. |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints: • Hip abduction strength of the injured leg at Week 26. • Change from baseline to Week 52 in lower extremity measure (LEM). • Lean Body Mass of the injured leg at Week 26 (dual-energy x-ray absorptiometry [DEXA]). • SPPB score at Week 52. • All-cause mortality rate.
Safety Endpoints: • Adverse events (AEs) and SAEs. • Safety laboratory data (hematology, biochemistry). • Vital signs. • Physical examination findings.
Tolerability Endpoints: • Proportion of subjects (%) who prematurely discontinued from the study. • Proportion of subjects (%) who prematurely discontinued from the study due to AEs. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Efficacy Endpoints: • Hip abduction strength of the injured leg: Weeks 6, 12, 26, 52 • Lower extremity measure (LEM): Day 5, Weeks 6, 12, 26, 52 • Lean Body Mass of the injured leg [DEXA]: Day 5 (retrospective collection of pre-fracture LEM at Day 5±1); Weeks 6, 26, 52 • SPPB score: Weeks 6, 12, 26, 52 • All-cause mortality rate: throughout the study
Safety Endpoints: • AEs and SAEs: throughout the study • Safety laboratory data (hematology, biochemistry): Screening, Days 1, 5; Weeks 6, 12, 26, 52 • Vital signs: Screening, Days 0, 1, 5; Weeks 6, 12, 26, 52 • Physical examination Screening, Day 5; Weeks 6, 12, 26, 52.
Tolerability Endpoints: throughout the study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Israel |
United States |
Bulgaria |
Germany |
Denmark |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the clinical study is defined as having occurred when the last subject has completed their final follow-up visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |