Pilot Clinical Trial of CPC/rhBMP-2 Microffolds as Bone Substitute for Bone Regeneration

Objective: The investigators initiated a pilot clinical study to test safety and preliminary efficacy in humans (bone tissue repairing capacity) and to evaluate standard clinical and rehabilitation protocols.

Summary Background Data: Bone tissue engineering scaffolds loading growth factors have been considered as the most perspective among all bone substitutes, yet little progress of its clinical translation has been made. The concept of "micro-scaffolds" was proposed in this study to provide a trajectory to its clinical translation.

Methods: Pre-cured CPC/rhBMP-2 micro-scaffolds have been successfully developed and further applied as an easy-to-operate filler for bone regeneration in a pilot clinical study. Patients of tibial plateau fractures, proximal humeral fractures, or calcaneal fractures at a similar level of severity were randomly divided into two groups and treated by CPC/rhBMP-2 microffolds or traditional CPC paste (control group).

Study Overview

• Status: Completed
• Conditions: Bone Fracture
• Intervention / Treatment: Procedure: Minimally invasive internal fixation surgeries; Device: CPC/rhBMP-2 micro-scaffolds; Device: CPC paste

Detailed Description

Objective: The investigators initiated a pilot clinical study to test safety and preliminary efficacy in humans (bone tissue repairing capacity) and to evaluate standard clinical and rehabilitation protocols.

Summary Background Data: Bone tissue engineering scaffolds loading growth factors have been considered as the most perspective among all bone substitutes, yet little progress of its clinical translation has been made. The concept of "micro-scaffolds" was proposed in this study to provide a trajectory to its clinical translation.

Methods: Pre-cured CPC/rhBMP-2 micro-scaffolds have been successfully developed and further applied as an easy-to-operate filler for bone regeneration in a pilot clinical study. Patients of tibial plateau fractures, proximal humeral fractures, or calcaneal fractures at a similar level of severity were randomly divided into two groups and treated by CPC/rhBMP-2 microffolds or traditional CPC paste (control group).

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 16~70 years.
2. Tibial plateau fractures, proximal humeral fractures, or calcaneal fractures at a similar level of severity.
3. An understanding of the rehabilitation protocol and willing to follow it.
4. An agreement to postoperative visits and tests.
5. Signed an informed subject consent form.

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPC/rhBMP-2; All operations were done by doctors titled with associate chief physician or above. Procedures were performed under general anesthesia in a tertiary care medical center. A minimally invasive internal fixation method had been applied in the surgeries. In brief, the patients with fracture were treated by reduction of fracture first of all, the correction of displacement, and the angle of the deformity, and the use of metal implants were fixed, and the collapse of the cancellous bone was filled with CPC/rhBMP-2 microffolds (product of Shanghai Rebone Biomaterials Co., Ltd, following the manufacturer's instruction), which was compacted and prevented from filling material into the joint cavity.	Procedure: Minimally invasive internal fixation surgeries; Device: CPC/rhBMP-2 micro-scaffolds
Active Comparator: CPC; All operations were done by doctors titled with associate chief physician or above. Procedures were performed under general anesthesia in a tertiary care medical center. A minimally invasive internal fixation method had been applied in the surgeries. In brief, the patients with fracture were treated by reduction of fracture first of all, the correction of displacement, and the angle of the deformity, and the use of metal implants were fixed, and the collapse of the cancellous bone was filled with CPC paste (product of Shanghai Rebone Biomaterials Co., Ltd, following the manufacturer's instruction), which was compacted and prevented from filling material into the joint cavity.	Procedure: Minimally invasive internal fixation surgeries; Device: CPC paste

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
X-ray	X-ray radiography at different time intervals after implantation was employed to observe the osseointegration of the implanted microffolds to host bone and the degradation of the material.	Pre-operation; 1, 2, 3, 4, 6, 8, 12, 18 and 24 months post-operation.
Clinical examination	The assessment was based on clinical examination. After the CPC implantation, all patients were observed according to the following indexes: allergic or toxic reactions, rash or high fever.	1 week post-operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Function scoring - IOWA knee score	The functional recovery was recorded at each follow-up time point using IOWA knee score in cases of tibial plateau fractures. The IOWA knee score is a questionnaire and clinical-examination-based evaluation of the function of the knee. The knee score is a five- category measurement, which includes activities of daily living, freedom from pain, gait, aid dependence, deformity and range of movement. The scores are grouped into excellent (90 to 100), good (80 to 89), fair (70 to 79) and poor (under 70) categories.	1, 2, 3, 4, 6, 8 and 12 months post-operation.
Function scoring - IOWA ankle score	The functional recovery was recorded at each follow-up time point using IOWA ankle score in cases of calcaneal fractures. The IOWA ankle score is a questionnaire and clinical-examination-based evaluation of the function of the ankle. The ankle score is a four-category measurement of function, freedom from pain, gait and range of movement. The scores are grouped into excellent (90 to 100), good (80 to 89), fair (70 to 79) and poor (under 70) categories.	1, 2, 3, 4, 6, 8 and 12 months post-operation.
Function scoring - NEER shoulder score	The functional recovery was recorded at each follow-up time point using Neer shoulder score in cases of proximal humeral fractures. Neer shoulder score has three parts: scoring of pain during the previous week by patients (verbal rating scale); clinical testing of function (muscle strength, reaching ability, and stability) and active range of motion; and an anatomical or radiological evaluation. The scores are grouped into excellent (90 to 100), good (80 to 89), fair (70 to 79) and poor (under 70) categories.	1, 2, 3, 4, 6, 8 and 12 months post-operation.

Collaborators and Investigators

• Sponsor: East China University of Science and Technology
• Collaborators: Shanghai Zhongshan Hospital; Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University; Shanghai 6th People's Hospital
• Investigators: Study Chair: Changsheng Liu, Ph.D., Engineering Research Center for Biomaterials of Ministry of Education, East China University of Science and Technology; Principal Investigator: Yuan Yuan, Ph.D., Engineering Research Center for Biomaterials of Ministry of Education, East China University of Science and Technology; Principal Investigator: Jinwu Wang, Ph.D., Ninth People's Hospital of Shanghai Jiao Tong University

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: November 17, 2015
• First Submitted That Met QC Criteria: November 18, 2015
• First Posted (Estimate): November 20, 2015

Study Record Updates

• Last Update Posted (Estimate): November 20, 2015
• Last Update Submitted That Met QC Criteria: November 18, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: bone substitute; rhBMP-2; CPC
• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone
• Other Study ID Numbers: CFDA No.(2013):3460199