Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study on Autologous Osteoblastic Cells Implantation to Early Stage Osteonecrosis of the Femoral Head

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01529008
Recruitment Status : Terminated (the interim results suggest that it is unlikely that the primary objective will be achieved at the final analysis)
First Posted : February 8, 2012
Last Update Posted : July 8, 2019
Sponsor:
Information provided by (Responsible Party):
Bone Therapeutics S.A

Tracking Information
First Submitted Date  ICMJE February 2, 2012
First Posted Date  ICMJE February 8, 2012
Last Update Posted Date July 8, 2019
Study Start Date  ICMJE November 2011
Actual Primary Completion Date May 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2017)
Percentage of treatment responders [ Time Frame: 24 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 6, 2012)
  • Pain scores on visual analog scale (WOMAC VA3.1 pain subscale) [ Time Frame: at 24 months ]
    WOMAC VA3.1 pain subscale
  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: at screening, D-28, D-21, D0, 1, 3, 6, 12, 18, 24, 36, 48 months ]
    During the whole study, subjects will be systematically assessed for the potential occurence of any AE or SAE, related to the product or related to the procedure, using patient open questionnaire, physical examination (including body mass index and vital signs), and laboratory measurements
  • Radiological progression to fractural stages [ Time Frame: at 24 month ]
    Radiological progression to fractural stages as assessed by conventional X-ray of the hip with reference to the ARCO classification
Change History Complete list of historical versions of study NCT01529008 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2017)
  • Percentage of treatment responders [ Time Frame: 6, 12, 18 and over 24 months follow-up period ]
  • Percentage of clinical responders [ Time Frame: 1, 3, 6, 12, 18, 24 and over 24 months follow-up period ]
  • percentage of radiological responders [ Time Frame: 6, 12, 18, 24 and over 24 months follow-up period ]
  • Absolute change from baseline in WOMAC VA1.3 total score [ Time Frame: 1, 3, 6, 12, 18, 24 and over 24 months follow-up period ]
  • Time to progression to fractural stage (ARCO III and higher) of the study treated hip [ Time Frame: 24 months ]
  • Time to hip arthroplasty [ Time Frame: 24 months ]
  • Percentage of patients requiring hip arthroplasty [ Time Frame: 1, 3, 6, 12, 18, 24 and over 24 months follow-up period ]
  • Absolute change from baseline in WOMAC VA1.3 composite pain subscale score [ Time Frame: 1, 3, 6, 12, 18, 24 and over 24 months follow-up period ]
  • Absolute change from baseline in WOMAC VA1.3 stiffness subscale score [ Time Frame: 1, 3, 6, 12, 18, 24 and over 24 months follow-up period ]
  • Absolute change from baseline in WOMAC VA1.3 functional subscale score [ Time Frame: 1, 3, 6, 12, 18, 24 and over 24 months follow-up period ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2012)
Secondary efficacy endpoints: WOMAC VA3.1 composite pain, stiffness, and function subscales, & time to arthroplasty [ Time Frame: at 24 months ]
  • WOMAC VA3.1 composite pain, stiffness, and function subscales
  • Time to arthroplasty
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study on Autologous Osteoblastic Cells Implantation to Early Stage Osteonecrosis of the Femoral Head
Official Title  ICMJE 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
Brief 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. 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.

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Osteonecrosis of the Femoral Head
Intervention  ICMJE
  • Drug: Core decompression/PREOB® implantation
    All patients will undergo a core decompression under general anesthesia combined with the implantation of PREOB® into the necrotic lesion (single administration).
  • Drug: Core decompression/placebo implantation
    All patients will undergo a core decompression under general anesthesia combined with the implantation of placebo into the necrotic lesion (single administration).
Study Arms  ICMJE
  • Experimental: Core decompression/PREOB® implantation
    Intervention: Drug: Core decompression/PREOB® implantation
  • Placebo Comparator: Core decompression/placebo implantation
    Intervention: Drug: Core decompression/placebo implantation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 3, 2019)
55
Original Estimated Enrollment  ICMJE
 (submitted: February 6, 2012)
130
Actual Study Completion Date  ICMJE November 2018
Actual Primary Completion Date May 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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:

    1. 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
    2. 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
    3. ARCO stage II associated or not with pain if necrotic angle sum is ≥190° based on sagittal and coronal MRI views
    4. 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)

Exclusion Criteria:

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.
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Netherlands,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01529008
Other Study ID Numbers  ICMJE PREOB-ON3
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bone Therapeutics S.A
Study Sponsor  ICMJE Bone Therapeutics S.A
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Bone Therapeutics S.A
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP