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.

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. - PREOB-NU3

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2011-005584-24-BE

Enrollment

176

Registered

2012-02-14

Start date

2012-05-10

Completion date

Unknown

Last updated

2017-10-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-infected hypotrophic non-union fractures of long bones MedDRA version: 20.0 Level: PT Classification code 10048617 Term: Pseudarthrosis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Interventions

Product Name: PREOB® 2 ml Product Code: PREOB® 2 ml Pharmaceutical Form: Suspension for injection in pre-filled syringe INN or Proposed INN: PREOB cells Current Sponsor code: PREOB cells Concentration

Eligibility

Sex/Gender

All

Inclusion criteria

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: - 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). - Present negative Urine Pregnancy tests at Visit #1 (Screening) and Visit #2 (Randomization / Baseline). If a Urine Pregnancy test will be 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

Exclusion criteria: - Non-union interline > 1 cm - 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 at 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 time of screening - Bone infection at site - Femoral neck fracture - Multifocal fracture/non-unions - Non-union or non-consolidated fracture on the neighbouring bone - RUS(T) > 9 as assessed by conventional CT scan - Global disease evaluation as assessed by the patient 6-lead or according to hospital standard care) at screening - Known history of severe acute or chronic allergy requiring medical therapy - Allergy to Gelfoam® - 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 including but not limited to local or metabolic bone diseases, Paget’s disease, fibromyalgia, haemochromatosis, acromegaly, ochronotic arthritis, heritable disorder, and collagen gene mutations. - Known severe osteoporosis - Current (or within 6 months of screening) illicit drug abuse - Current or past treatment for cancer or blood dyscrasia, including any chemotherapy, radiotherapy, immunotherapy, biotherapy, haematopoietic growth factors, anti-vasculogenesis, and/or anti-angiogenesis treatment - Current (or within 1 month of screening) anticoagulants, including intravenous, intramuscular, subcutaneous, and oral anticoagulation at any therapeutic dosage (but not prophylactic use) - Current or past intravenous bisphosphonate therapy - Current (or within 6 months of screening) oral bisphosphonate therapy - Current (or within 1 month of screening) treatment with calcitonin, raloxif

Design outcomes

Primary

Measure	Time frame
Main Objective: The main objectives of the study are to demonstrate the non-inferiority of PREOB® implantation over bone autograft in terms of safety and efficacy at Month 12 clinically on the basis of the global disease evaluation score (as assessed by visual analogue scales) and radiologically on the basis of the percentage of patients with radiological improvement as assessed by RUST score determined by CT Scan.;Secondary Objective: The secondary objective is to compare PREOB® and the Bone Autograft in terms of efficacy using: - Global Disease Evaluation as perceived by the physician using a Visual Analogue Scale - Pain using a visual analogue scale (at rest, during activities and at palpation) - Weight-bearing using a Likert Scale - Well-being score as assessed by the SF-12 questionnaire - Radiological improvement using the RUS(T) as assessed by X-ray.;Primary end point(s): - Global patient evaluation as perceived by the patients using a visual analogue scale - Radiological healing progression using the RUS(T) as assessed by CT scan At each follow-up visit, subjects will be assessed for the potential occurrence of any AE or SAE, related to the product or related to the procedure, using patient open non-directive questionnaire, vital signs and laboratory measurements.;Timepoint(s) of evaluation of this end point: Efficacy endpoints will be determined at each scheduled visit over the 12-month follow-up period (notably at 1, 3, 6, 9 and 12 months) for patients in the PREOB® implantation or Bone Autograft groups.	—

Measure

Time frame

Main Objective: The main objectives of the study are to demonstrate the non-inferiority of PREOB® implantation over bone autograft in terms of safety and efficacy at Month 12 clinically on the basis of the global disease evaluation score (as assessed by visual analogue scales) and radiologically on the basis of the percentage of patients with radiological improvement as assessed by RUST score determined by CT Scan.;Secondary Objective: The secondary objective is to compare PREOB® and the Bone Autograft in terms of efficacy using: - Global Disease Evaluation as perceived by the physician using a Visual Analogue Scale - Pain using a visual analogue scale (at rest, during activities and at palpation) - Weight-bearing using a Likert Scale - Well-being score as assessed by the SF-12 questionnaire - Radiological improvement using the RUS(T) as assessed by X-ray.;Primary end point(s): - Global patient evaluation as perceived by the patients using a visual analogue scale - Radiological healing progression using the RUS(T) as assessed by CT scan At each follow-up visit, subjects will be assessed for the potential occurrence of any AE or SAE, related to the product or related to the procedure, using patient open non-directive questionnaire, vital signs and laboratory measurements.;Timepoint(s) of evaluation of this end point: Efficacy endpoints will be determined at each scheduled visit over the 12-month follow-up period (notably at 1, 3, 6, 9 and 12 months) for patients in the PREOB® implantation or Bone Autograft groups.

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Secondary

Measure	Time frame
Secondary end point(s): - Pain using visual analogue scale - Weight bearing using a likert scale - Well-being score as assessed by SF 12 - Global disease evaluation as perceived by the physician using a visual analogue scale - Radiological improvements using the RUS(T) as assessed by X-Ray ;Timepoint(s) of evaluation of this end point: Efficacy endpoints will be determined at each scheduled visit over the 12-month follow-up period (notably at 1, 3, 6, 9 and 12 months) for patients in the PREOB® implantation or in the Bone Autograft groups.	—

Measure

Time frame

Secondary end point(s): - Pain using visual analogue scale - Weight bearing using a likert scale - Well-being score as assessed by SF 12 - Global disease evaluation as perceived by the physician using a visual analogue scale - Radiological improvements using the RUS(T) as assessed by X-Ray ;Timepoint(s) of evaluation of this end point: Efficacy endpoints will be determined at each scheduled visit over the 12-month follow-up period (notably at 1, 3, 6, 9 and 12 months) for patients in the PREOB® implantation or in the Bone Autograft groups.

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Countries

Belgium, Netherlands

Contacts

Public ContactClinical Trial Information

Bone Therapeutics S.A.

preob.nu3@bonetherapeutics.com

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026