A pivotal Phase IIb/III, multicentre, randomised, open, controlled study on the efficacy and safety of autologous osteoblastic cells (PREOB®) implantation in non-infected hypotrophic non-union fractures.

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 176

Inclusion Criteria

- Patient diagnosed with a non-infected hypotrophic (atrophic and oligotrophic) non-union fracture of a long bone which will be of a minimum 6 months without signs of evolution over the last 3 months at the time of randomisation/baseline
- Patient aged 18 to 65 years inclusive
- Patient capable to understand and comply with study requirements
- Patient capable to provide a written, dated, and signed informed consent prior to any study procedure for participation in the study and transmission of personal anonymized data.
- Normal haematology function, defined in a peripheral blood testing as leukocytes >3000/mm³, absolute neutrophils count >1500/mm³ and platelets >140,000/mm³

Female patients must be:
- Post-menopausal (defined as at least 12 month post-cessation of menses), or
- Surgically sterile, or
- For women with childbearing potential:
1. Using reliable contraceptive method for at least 6 weeks prior to screening and during the whole study period. Reliable contraceptive methods include orally administered hormonal contraceptives, surgical intervention (e.g., tubal ligation), and intrauterine device (IUD).
2. Present negative Urine Pregnancy tests at Visit #1 and Visit #2. If a Urine Pregnancy test is positive at any other of the following visits, the patient is excluded from the study.

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 176
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Non-union interline > 1 cm as defined by the independent radiologist
- Insufficient reduction of the fracture with displaced fragments
- Insufficient fracture stability due, for example, to an osteolysis at the level of the nails/screws and/or defect and/or mobility of the osteosynthesis material at physical examination, as judged by the Investigator
- Osteosynthesis material revision performed less than 3 months from the randomization/baseline visit for simple revision without surgery or bone graft at the non-union site or less than 6 months from the randomization/baseline visit for revision with surgery or bone graft on the non-union site
- Osteosynthesis materials at the non-union site other than intramedullary nails, screws, plates or external fixation
- Open fracture with septic local infection and/or abnormal CRP and/or abnormal skin and scar, at the point of screening
- Bone infection at site
- Femoral neck fracture
- Multifocal fracture/non-unions (i.e., more than one non-union fracture site on the studied bone)
- Non-union or non-consolidated fracture on the neighbouring bone (i.e., at radius/ulna or at tibia/fibula)
- RUS(T) > 9 as assessed by conventional X-ray
- Global disease evaluation as assessed by the patient lower than 20 mm on a visual analogue scale
- Nerve damage and/or neuropathic/neuropathic-like pain at non-union fracture site
- Tendon lesion (e.g., rupture or enthesopathy) at non-union fracture site
- Positive serology for hepatitis B
- Positive serology for hepatitis C
- Positive serology for HIV
- Positive serology for syphilis
- Positive serology for HTLV-1
- Presence, or previous history, of risks factors for diseases caused by prions, including patients diagnosed with Creutzfeldt-Jakob disease, or variant Creutzfeldt-Jakob disease (including bovine spongiform encephalopathy), or having a family history of non-iatrogenic Creutzfeldt-Jakob disease; patients with a history of rapid progressive dementia or degenerative neurological disease (including those of unknown origin); recipients of hormones derived from the human pituitary gland (such as growth hormones); and recipients of grafts of cornea, sclera, and dura mera)
- Global sepsis, including, but not limited to brucellosis, typhus, leprosy, relapsing fever, melioidosis and tularaemia
- Haemoglobin level <10 g/dl
- History of blood loss exceeding 450 ml (incl. blood donations) within 1 month before screening
- Renal impairment, defined as serum creatinine >2 mg/dl or 176 µmol/L
- Hepatic impairment, defined as alanine aminotransferase or aspartate aminotransferase >3 times the upper normal limit
- Poorly controlled diabetes mellitus (defined as HbA1C >8%)
- Clinically relevant abnormal ECG (> 6-lead or according to standard of care at the hospital) at screening, as judged by the Investigator
- Known history of severe acute or chronic allergy requiring medical therapy
- Known allergy to Gelfoam® (i.e., porcine collagen)
- Known allergy to gentamicin
- Current or past history of solid or haematological neoplasia or bone marrow transplantation
- Life expectancy less than 6 months
- Current medical disease that could interfere with the evaluation of efficacy, as judged by the investigator, including but not limited to local or metabolic bone diseases (e.g., osteogenesis imperfecta, primary hyperparathyroidism, renal osteodystrophy, fibrous dysplasia [monostotic, polyostotic McCune-Albright syndrome] and osteopetrosis), Paget’s disease, fibromyalgia

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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