Autologous Osteoblastic Cells Implantation to Early Stage Osteonecrosis of the Femoral Head (PREOB-ON2)

Treatment of Osteonecrosis of the Femoral Head by Implantation of Preosteoblastic Cells: a Randomized, Controlled, Single Blind Pilot Study

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 2B study aims at demonstrating the efficacy and safety of PREOB® in the treatment of early stage osteonecrosis of the femoral head. The primary goal of this study was to investigate the safety and efficacy of the implantation of the investigational product PREOB® (human autologous bone marrow-derived osteoblastic cells) in comparison to bone marrow concentrate (BMC) when implanted at the osteonecrotic lesion of the femoral head, with a follow-up period of up to 5 years.

Study Overview

• Status: Completed
• Conditions: Avascular Necrosis of Femur Head
• Intervention / Treatment: Drug: Core decompression/PREOB® implantation; Drug: Core decompression/BMC implantation

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Investigative site 01
  • Liege, Belgium
    • Investigative site 02

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ARCO stage I or II non-traumatic osteonecrosis of the femoral head, confirmed by conventional X-ray and magnetic resonance imaging (MRI) of the hip
• Aged 18 or higher
• Ability to provide a written, dated and signed informed consent prior to any study-related procedure to understand and comply with study requirements

Exclusion Criteria:

• Evidence of malignant disorder in the past five years
• Positive serology for hepatitis B, hepatitis C, HIV
• Patient unable to undergo a MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Core decompression/PREOB® implantation; Core decompression/autologous osteoblastic cells (PREOB®) implantation	Drug: Core decompression/PREOB® implantation; All subjects received a core decompression under general anesthesia combined with the implantation of PREOB® into the necrotic lesion (single administration).
Active Comparator: Core decompression/BMC implantation; Core decompression/bone marrow concentrate (BMC) implantation	Drug: Core decompression/BMC implantation; All subjects received a core decompression under general anesthesia combined with the implantation of BMC into the necrotic lesion (single administration).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of responder subjects	Response defined as the absence of progression to fractural stage (ARCO stage III or higher) & a clinically significant pain improvement	24 months
Potential occurrence of any AE or SAE, related to the product or to the procedure, using patient open non-directive questionnaire, physical examination and laboratory measurements		60 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of responder subjects	3, 6, 12 and 36 months
Percentage of subjects progressing to fractural stage (ARCO stage III or higher), as assessed by conventional X-ray	3, 6, 12, 24 and 36 months
Change from baseline in VAS pain score	3, 6, 12, 18, 24, 36 and 48 months
Change from baseline in WOMAC® score	3, 6, 12, 18, 24, 36 and 48 months
Change from baseline in Lequesne score	3, 6, 12, 18, 24, 36 and 48 months
Proportion of subjects undergoing a total hip arthroplasty	6, 12, 24 and 36 months
Time to hip fracture	36 months

Collaborators and Investigators

• Sponsor: Erasme University Hospital
• Collaborators: University of Liege; Bone Therapeutics S.A

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: August 25, 2016
• First Submitted That Met QC Criteria: August 31, 2016
• First Posted (Estimate): September 7, 2016

Study Record Updates

• Last Update Posted (Estimate): September 7, 2016
• Last Update Submitted That Met QC Criteria: August 31, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Bone; Hip; Musculoskeletal Disorders; Orthopedics; Osteonecrosis; Femoral Head
• Additional Relevant MeSH Terms: Pathologic Processes; Musculoskeletal Diseases; Bone Diseases; Necrosis; Legg-Calve-Perthes Disease; Osteonecrosis; Femur Head Necrosis
• Other Study ID Numbers: 2003/281

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No