E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Osteonecrosis of the Femoral Head |
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E.1.1.1 | Medical condition in easily understood language |
Osteonecrosis of the Femoral Head |
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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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031264 |
E.1.2 | Term | Osteonecrosis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The study objectives are to demonstrate that Core decompression/PREOB® implantation is superior to Core decompression/Placebo implantation in relieving clinical hip symptoms and halting (or reverting) radiological progression (to fractural stages III or higher) at 24 months.
Patients will be assessed using the Western Ontario and McMaster Universities (WOMAC®) Index. Central radiological evaluation will include conventional bilateral X-ray and MRI of the hips to assess ARCO Staging and to measure the sum of the coronal and sagittal necrotic angles. |
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E.2.2 | Secondary objectives of the trial |
Exploratory Efficacy Endpoints include • Change from baseline in necrotic lesion of the treated hip volume as assessed by MRI • Radiological evolution of contralateral hip over time as assessed by conventional X-ray • Assessment of serum biomarkers • Impact of osteonecrosis etiology: corticoid-induced, alcohol abuse, or idiopathic forms of osteonecrosis
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men or women between 18 and 70 years (inclusive) 2. Ability to provide a written, dated, and signed informed consent prior to any study related procedure and to understand and comply with study requirements 3.Diagnosis of Osteonecrosis: a.ARCO stage I associated with WOMAC® VA3.1 pain score ≥20 mm and necrotic angle sum ≥190° based on sagittal and coronal MRI views or b.ARCO stage II associated with WOMAC® VA3.1 pain score ≥20 mm if necrotic angle sum <190° based on sagittal and coronal MRI views or c.ARCO stage II associated or not with pain if necrotic angle sum is ≥190° based on sagittal and coronal MRI views d.Associated with corticosteroid and/or with alcohol abuse and/or idiopathic. 4.Normal haematology function, defined as: leukocytes ≥3000/mm3, absolute neutrophils count ≥1500/mm3, platelets ≥140,000/mm3, and haemoglobin concentration ≥10g/dl (peripheral blood test) |
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E.4 | Principal exclusion criteria |
1.Exclusively diaphyseal or metaphyseal osteonecrotic lesion 2.Traumatic or hyperbaric osteonecrosis, or osteonecrosis associated with hemoglobinopathy or coagulopathy (e.g., thalassemia, sickle cell disease,…), or Gaucher’s disease 3.Osteoarthritis at the hip under evaluation defined as Kellgrens stage ≥2, as assessed by the Central Radiologist 4.Patients suffering from any medical conditions interfering with patient’s pain evaluation of the hip under evaluation, such as knee arthritis 5.Bone fracture or bone infection at hip under evaluation 6.Patients who are candidates for any predictable joint replacement on the hip that is evaluated 7.Active hepatitis B (defined as positive HBs Ag and/or positive PCR), active hepatitis C (defined as positive PCR), positive serology for HIV , or Syphilis1, or HTLV-11 8.Presence, or previous history, of risks factors for diseases caused by prions, and recipients of grafts of cornea, sclera, and dura mater 9.History of blood loss exceeding 450 ml (incl. donations) within 1 month of screening 10.Renal impairment defined by an estimated creatinine clearance value < 30 ml per min, calculated with the Cockcroft-Gault formula 11.Hepatic impairment, defined as alanine aminotransferase or aspartate aminotransferase ≥ 3 times the upper limit of normal 12.Poorly controlled diabetes mellitus, defined as HbA1C > 9% 13.Global sepsis 14.Allergy to gentamicin or porcine collagen or any substance or device the patient might be exposed to in the context of the study related interventions (i.e., bone marrow harvesting and implantation), as judged by the Investigator 15. History of hypersensitivity to human biological material, including blood and blood derived products, documented clinically or by laboratory tests 16.Current or past history of solid or haematological neoplasia (except for basal cell carcinoma of the skin and for carcinoma in situ of the cervix that has been treated with no evidence of recurrence) 17.History of bone marrow transplantation 18.Patients with a life expectancy less than 2 years, as judged by the Investigator 19.Patients treated by core decompression of the hip under evaluation within 6 months of screening 20.Treatment with doses of prednisolone ≥15 mg per day (or equivalent) within 1 month from screening, and patients with anticipated needs of daily corticoid doses ≥15 mg prednisone (or equivalent) in the 6-month period following PREOB®/Placebo implantation 21.Illicit drug or alcohol abuse interfering with patient’s ability to understand and comply with study requirements, as judged by the Investigator 22.Pregnancy 23.Breast-feeding 24.Patients unable to undergo MRI, e.g. patients with pace-maker, intra-ocular or intra-cerebral metallic foreign bodies, and mechanical artificial heart valves
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoints • Change form baseline in WOMAC® VA3.1 pain susbcale score, and • Percentage of patients progressing to fractural stages (ARCO III or higher) as assessed by conventional X-ray
Safety Endpoints During the whole study, subjects will be systematically assessed for the potential occurrence of any AE or SAE, related to the product or related to the procedure, using patient interview, physical examination (including body mass index and vital signs), and laboratory measurements. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary Efficacy Endpoints: at month 24
Safety endpoints: at every visit, up to month 48 |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints • Change from baseline in WOMAC® VA3.1 total score and composite pain, stiffness, and function subscales scores • Percentage of patients progressing to fractural stages (ARCO stage III or higher), as assessed by conventional X-ray • Time to hip fracture • Time to arthroplasty • Percentage of patients requiring hip arthroplasty
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Efficacy Endpoints: up to month 24 |
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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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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Last visit of the last subject undergoing the trial |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |