Comparative Study of Gene-activated Bone Substitute and Autobone in Treatment of Long Bone Nonunions

• Conditions: Non Union Fracture; Non-Union of Ankle Joint Without Infection
• Interventions: Combination Product: "Histograft", a bone substitute based on octacalcium phosphate (OCP) and plasmid DNA encoding VEGFA gene

• Registration Number: NCT04705857
• Lead Sponsor: Histograft Co., Ltd.

Brief Summary

The study is aimed to compare the effectiveness of "Histograft" bone substitute (gene-activated bone substitute based on octacalcium phosphate and plasmid DNA encoding VEGFA gene) mixed with shredded autobone and pure shredded auto bone harvested from iliac crest in treatment of patients with long bone nonunions

Detailed Description

An open-label randomized controlled clinical trial, two cohorts. Patients who met the inclusion criteria are planned to be enrolled into the trial. Upon enrollment, all patients will undergo screening, a set of clinical examination, instrumental investigations and laboratory tests, including CT of the affected bone with the assessment of nonunion.

All patients enrolled in the study will be subjected to bone reconstructive surgery with nonunion excision and bone grafting with either investigational bone substitute mixed with shredded autobone (in a ratio of 50/50) harvested during the surgery or pure shredded autobone from iliac crest.

The clinical study results will be evaluated at the time points of 1, 15, 45, 90, 180 days with clinical examination, instrumental investigations and laboratory tests. Control CT will be carried out for the primary outcome measure at 90, 180, 360 days after surgery.

Study Timeline

• Status Verified: 2020-08
• Study Start: 2020-08-01
• Study First Submitted: 2021-01-11
• Study First Submitted QC: 2021-01-11
• Last Update Submitted: 2021-01-11
• Study First Posted: 2021-01-12
• Last Update Posted: 2021-01-13
• Primary Completion: 2022-08-01
• Study Completion: 2022-09-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• traumatic isolated closed or open Gustilo I and II, IIIA and IIIB humerus, tibial or femur diaphyseal or metaphysodiaphyseal fracture with a status of atrophic, oligotrophic or normotrophic non-union;
• signed voluntary informed consent

Exclusion Criteria

• hypertrophic non-union;
• disability or unwillingness to give a voluntary informed consent or follow requirements of the clinical trial;
• segmental bone loss requiring specific therapy (bone transport, vascularized graft, large structural allograft, megaprosthesis, etc);
• other fractures causing interference with weight bearing;
• visceral injuries or diseases interfering with callus formation (severe cranioencephalic trauma, etc.);
• unrecovered vascular or neural injury;
• infection of any location and aetiology;
• pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control;
• malignant tumour (past history or concurrent disease);
• history of bone harvesting on iliac crest contraindicating new iliac crest bone graft harvesting or bone marrow collection;
• conditions limiting study compliance (e.g., dementia, psycho-neurological diseases, drug addiction, and alcoholism);
• medication affecting bone turnover (oral bisphosphonates, PTH, sodium fluoride, strontium ranelate, calcitonin, testosterone, systemic cortico- or anabolic steroids)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
test group	"Histograft", a bone substitute based on octacalcium phosphate (OCP) and plasmid DNA encoding VEGFA gene	bone reconstructive surgery with the use of "Histograft" bone substitute (gene-activated matrix based on octacalcium phosphate and plasmid DNA encoding VEGFA gene) mixed with shredded autobone (in a ratio of 50/50) harvested during the surgery

Primary Outcome Measures

Name	Time	Method
Bone consolidation	12 months	Radiographic assessment of bone healing using REBORNE scale

Secondary Outcome Measures

Name	Time	Method
Ability to use the operated limb	12 months	Clinical assessment using DASH scale (for upper limb) or LEFS scale (for lower limb)
Pain level	12 months	Level of pain measured using Numeric Rating Scale
Adverse Events and Serious Adverse Events	12 months	Evaluation of the Adverse Events and Serious Adverse Events frequency

Trial Locations

Locations (1)

S.M. Kirov Military Medical Academy, Department of Traumatology and Orthopaedics; 🇷🇺 Saint Petersburg, Russian Federation