Early avascular necrosis of the femoral head (MRI diagnosis): Ficat and Arlet 0, 1, or 2 (Steinberg stages 0, I, IIA, IIB, or IIC) MedDRA version: 14.1 Level: SOC Classification code 10028395 Term: Musculoskeletal and connective tissue disorders System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders MedDRA version: 14.1 Level: LLT Classification code 10003860 Term: Avascular necrosis femoral head System Organ Class: 10028395 - Musculoskeletal and connective tissue disor
Conditions
Interventions
Product Name: Cultured Mesenchymal Cells from bone marrow isolation
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Cultured autologous bone marrow stem adult Mesenchymal Cells expa
Sponsors
Universidad Autónoma de Madrid
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Age 18 to 65, both sexes -Early avascular necrosis of the femoral head (MRI diagnosis): Ficat and Arlet 0, 1, or 2 (Steinberg stages 0, I, IIA, IIB, or IIC) -Symptomatic osteonecrosis with less than 6 months of evolution -Able to provide informed consent, and signed informed consent -Medical health care coverage -Able to understand and accept the study constraints Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: -Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control. -Participation in another therapeutic trial in the previous 3 months -Stages 3 or more (Ficat and Arlet) or III or more (Steinberg) of severe femoral head osteonecrosis, primarily based on diagnosis by imaging (X-Rays, MRI). -Flattening or collapse of the femoral head (Steinberg stage IV) or articular cartilage collapse at the time of core decompression surgery. -Septic arthritis. -Stress fracture. -Non-osteonecrosis metabolic bone diseases (particularly Paget's disease of bone, osteogenesis imperfecta, primary hyperparathyroidism, fibrous dysplasia monostotic, polyostotic McCune-Albright syndrome] and osteopetrosis). -Any active bisphosphonate treatment or any history of intravenous (IV) treatment. -History of prior or concurrent diagnosis of HIV-, Hepatitis-B- or Hepatitis-C-infection (confirmed by serology or PCR) -Active hepatitis B or hepatitis C infection at the time of screening. Known allergies to products involved in the production process of MSC. -History of neoplasia or current neoplasia in any organ. -Corticoid or immunosuppressive therapy more than one week in the two months prior to study inclusion -Patients who will require continuous, systemic, high dose corticosteroid therapy (more than 7.5 mg/day) within 6 months after surgery. -Patients who are in active treatment for cancer or blood dyscrasia, or have received chemotherapy, radiotherapy or immunotherapy in the past 2 years. -History of regular alcohol consumption exceeding 2 drinks/day (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of hard liquor) within 6 months of screening and/or history of illicit drug use. -Serum AST (SGOT)/ALT (SGPT) > 2.5 X (institutional standard range). -MRI-incompatible internaldevices (pacemakers, aneurysm clips, etc). -Body mass index (BMI) of 40 kg/m² or greater. -Patients unable to tolerate general anesthesia defined as an American Society of Anesthesiologists (ASA) criteria of > 2. -Insulin dependent diabetes -Patients with poorly controlled diabetes mellitus (HbA1C > 8%), or with peripheral neuropathy, or known concomitant vascular problems. -Patients receiving treatment with hematopoietic growth factors or anti-vasculogenesis or antiangiogenesis treatment. -Traumatic osteonecrosis. -Adult in the care of a guardian (Subject legally protected) -Impossibility to meet at the appointments for the clinical follow up.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and feasibility of the treatment of early avascular necrosis of the femoral head with expanded bone marrow autologous stem cells to enhance bone healing, after core decompression through percutaneous forage;Secondary Objective: To obtain bone healing, without increasing the complication rate, of early avascular necrosis of the femoral head treated by standard care procedures plus percutaneous injection of autologous stem cells derived from bone marrow and expanded under GMP conditions.;Primary end point(s): Safety endpoints include: -Early local complication rate, as the percentage of patients with local complications within three months after surgery. - Global complication rate, as the percentage of patients with local or general complications at 52 weeks ;Timepoint(s) of evaluation of this end point: Complication rates at weeks : 6, 12, 24, 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Local and general complication rate at 104 weeks regarding potential effects in the FU of patients after introducing MSCs ?-Number of patients with no progression to the next stage (defined as 0 to 1, 1 to 2, 2 to 3) at 12 months. ?-Number of patients with no radiological or MRI progression at 6 weeks (X-ray), 12 weeks (X-ray, MRI), 24 weeksX-ray), and 52 weeks (X-ray, MRI), in proportion of the recruited, treated patients. Data and images will be reviewed by an adjudication committee at the end of the study following a pre established procedure -Amount of necrotic bone in the femoral head at 12 weeks and 52 weeks in MRI, compared with preoperative status. This will be measured according to a standardised protocol. -Changes in serum levels of bone turnover markers(in a centralized laboratory) at 12 and 24 weeks after treatment -Pain assessed by a Visual Analogue Scale at 12 , 24 and 52 weeks ;Timepoint(s) of evaluation of this end point: 6, 12, 24, 52 and 104 weeks | — |
Countries
Germany, Italy, Romania, Spain
Contacts
Public ContactDra. Cristina Avendaño
Dept of Clinical Pharmacology-Universitary Hospital Puerta de Hierro
Outcome results
None listed