Osteonecrosis of the Femoral HeadPhase 3NCT01529008
Study on Autologous Osteoblastic Cells Implantation to Early Stage Osteonecrosis of the Femoral Head
A Phase 3 study testing Core decompression/PREOB® implantation in people with Osteonecrosis of the Femoral Head, run by Bone Therapeutics S.A.
Trial summary
Non-traumatic osteonecrosis is a painful disorder of the hip characterized by a necrosis of the osteomedullary tissue, which leads to subchondral bone collapse and joint destruction. Core decompression is currently the treatment of choice for early stage osteonecrosis of the femoral head. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Osteonecrosis of the Femoral Head
- What is being tested?
- Core decompression/PREOB® implantation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- No sites listed yet
- Study dates
- Nov 2011to Nov 2018
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women between 18 and 70 years (inclusive) with a diagnosis of ARCO Stage I or II non-traumatic osteonecrosis of the femoral head, confirmed by central imaging analysis based on X-ray and MRI.
- Ability to provide a written, dated, and signed informed consent prior to any study related procedure and to understand and comply with study requirements
- Diagnosis of Osteonecrosis:
- 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
- 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
- ARCO stage II associated or not with pain if necrotic angle sum is ≥190° based on sagittal and coronal MRI views
- Associated with corticosteroid and/or with alcohol abuse and/or idiopathic
- 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)
Who cannot join
- Current symptoms and/or signs related to the disease under study
- Exclusively diaphyseal or metaphyseal osteonecrotic lesion
- Traumatic or hyperbaric osteonecrosis, or osteonecrosis associated with hemoglobinopathy or coagulopathy (e.g., thalassemia, sickle cell disease,…), or Gaucher's disease
- Any other focal or diffuse bone marrow lesion
- Osteoarthritis at the target hip defined as Kellgrens stage ≥2, as assessed by the Central Radiologist
- Patients suffering from any medical conditions interfering with patient's pain evaluation of the hip under evaluation, such as knee arthritis.
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- Bone fracture or bone infection at hip under evaluation.
- Patients who are candidates for any predictable joint replacement on the hip that is evaluated Current or previous diagnoses, signs and/or symptoms
- Active hepatitis B (defined as positive HBs Ag and/or positive PCR), or active hepatitis C (defined as positive PCR), positive serology for HIV, or Syphilis, or HTLV-1, and any other tests that may be required by the authorities in case of a new disease outbreak that can affect the safety of the physicians and operators at the time of patient screening.
- Presence, or previous history, of risks factors for diseases caused by prions, and recipients of grafts of cornea, sclera, and dura mater
- History of blood loss exceeding 450 ml (incl. donations) within 1 month of screening
- Renal impairment defined by an estimated creatinine clearance value < 30 ml per min, calculated with the Cockcroft-Gault formula
- Hepatic impairment, defined as alanine aminotransferase or aspartate aminotransferase ≥ 3 times the upper limit of normal
- Poorly controlled diabetes mellitus, defined as HbA1C > 9%
- Global sepsis
- 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
- History of hypersensitivity to human biological material, including blood and blood derived products, documented clinically or by laboratory tests
- 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)
- History of bone marrow transplantation
- Patients with a life expectancy less than 2 years, as judged by the Investigator Current or previous treatment
- Patients having participated in another clinical trial within 3 months of screening
- Patients previously treated with PREOB®
- Patients treated by core decompression of the hip under evaluation within 6 months of screening
- 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
- Illicit drug or alcohol abuse interfering with patient's ability to understand and comply with study requirements, as judged by the Investigator
- Safety aspects concerning female patients of childbearing potential
- Pregnancy
- Breast-feeding
- Women with childbearing potential not willing or able to use 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).
- Other exclusion criteria:
- Body Mass Index (BMI) ≥ 35 kg/m2
- Patients unable to undergo MRI, e.g. patients with pace-maker, intra-ocular or intra-cerebral metallic foreign bodies, and mechanical artificial heart valves
- Patients unable to undergo general anaesthesia or surgical intervention
About this study
Official title: Phase 3, Pivotal, Multicentre, Randomised, Double-blind Controlled Study to Evaluate the Efficacy and Safety of Autologous Osteoblastic Cells (PREOB®) Implantation in Early Stage Non Traumatic Osteonecrosis of the Femoral Head
Non-traumatic osteonecrosis is a painful disorder of the hip characterized by a necrosis of the osteomedullary tissue, which leads to subchondral bone collapse and joint destruction. Core decompression is currently the treatment of choice for early stage osteonecrosis of the femoral head. This method consists in decompressing the rigid intra-osseous chamber to promote revascularization, thus halting progression of the disease and stimulating repair. Still this treatment remains highly controversial, since the success rates of the first studies have not been repeated.
The exact pathology mechanisms involved in osteonecrosis have not yet be fully elucidated. Several hypotheses have been evoked, including fat embolism, trabecular bone microfractures, microvascular tamponade and, more recently, impaired bone and/or mesenchymal cells recruitment.
Read more
Three studies have indicated the potential clinical benefits of cell-based approaches for the treatment of osteonecrosis (Hernigou 1997, Hernigou \& Beaujean 2002, Gangji et al. 2004). This is on the basis of these observations that a proprietary population of autologous osteoblastic cells (PREOB®) has been developed.
This Phase 3 study aims at demonstrating the efficacy and safety of PREOB® in the treatment of early stage osteonecrosis of the femoral head. More specifically, the purpose of the study is to demonstrate that core decompression/PREOB® implantation into the necrotic lesion is superior to core decompression/placebo implantation in relieving hip symptoms and halting (or reverting) radiological progression of the disease.
- Conditions
- Osteonecrosis of the Femoral Head
- Being tested
- Core decompression/PREOB® implantation, Core decompression/placebo implantation
- Keywords
- Osteonecrosis, Femoral Head, Hip, Orthopedics, Bone, Musculoskeletal Disorders
- Medical subject headings
- Legg-Calve-Perthes Disease, Osteonecrosis, Musculoskeletal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Core decompression/PREOB® implantationDrug
All patients will undergo a core decompression under general anesthesia combined with the implantation of PREOB® into the necrotic lesion (single administration).
Core decompression/placebo implantationDrug
All patients will undergo a core decompression under general anesthesia combined with the implantation of placebo into the necrotic lesion (single administration).
| Study group | Role | What they receive |
|---|---|---|
| Core decompression/PREOB® implantation | Experimental | Not described Receives: Drug: Core decompression/PREOB® implantation |
| Core decompression/placebo implantation | Placebo comparator | Not described Receives: Drug: Core decompression/placebo implantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Treatment Responders
A patient was considered as having responded to treatment if:
- the WOMAC VA3.1 pain subscale score (Western Ontario and McMaster Universitie Visual Analogue scale) of the study treated hip improved from baseline by at leat the MCID (minimal clinically important difference ) the WOMAC VA3.1 pain subscale score is Visual score based on 10 cm and
- the study treated hip did not progress to fractural stages (ARCO III or higher) as assessed by conventional X-ray
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2012 (estimated)
- Study startNov 2011
- Primary completionMay 2017
- Study completionNov 2018
Why it stopped: the interim results suggest that it is unlikely that the primary objective will be achieved at the final analysis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Osteonecrosis of the Femoral HeadStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bone Therapeutics S.A
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01529008
- Sponsor's protocol ID
- PREOB-ON3
- Status last verified
- Jun 2022
- First submitted
- 2 Feb 2012
- Last updated
- 24 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Jayankura M, Thomas T, Seefried L, Dubrana F, Gunther KP, Rondia J, Davis ET, Winnock de Grave P, Carron P, Gangji V, Vande Berg B, Godeaux O, Sonnet W. Does Adjunction of Autologous Osteoblastic Cells Improve the Results of Core Decompression in Early-stage Femoral Head Osteonecrosis? A Double-blind, Randomized Trial. Clin Orthop Relat Res. 2023 Aug 1;481(8):1527-1540. doi: 10.1097/CORR.0000000000002610. Epub 2023 Mar 24.
PubMed 36961220