Bone SubstitutesNCT03884790
Pre-market Study to Evaluate Safety and Performance of GreenBone Implant (Long Bone Study)
A study testing surgical repair of long bone defects in people with Bone Substitutes and Bone Defect, run by GreenBone Ortho S.p.A. at 8 sites in 6 countries.
Trial summary
Multi-center, international, prospective, open-label, single-arm, first-in-human clinical investigation. The Patients enrolled in this clinical investigation will undergo a scheduled surgery for the treatment of long bone defects up to 6 cm using GreenBone Implant. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bone Substitutes, Bone Defect
- What is being tested?
- surgical repair of long bone defects
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 8 sitesin 6 countries
- Study dates
- 22 Jan 2019to 8 Jun 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female Patients.
- Patients aged ≥ 18 and ≤ 65 years old.
- Patients requiring long bone defect reconstructions up to 3 cm, resulting from high-energy traumatic events, or from the treatment of complex bone non-unions in the extremities (arms and legs), or patients undergoing the second stage of the Masquelet technique.
- Patients understanding the nature of the study and providing their informed consent to participation.
- Patients willing and able to attend the follow-up visits and procedures foreseen by study protocol.
- Please note: after interim analysis review by the DSMB, inclusion criteria n. 3 will be modified as follows (all Investigators will be notified by the Sponsor, and adequate training by Clinical Research Associate-CRA will be conducted):
- Change of inclusion criteria n. 3: Patients requiring long bone defect reconstructions longer than 3 cm and up to 6 cm, resulting from high-energy traumatic events, or from the treatment of complex bone non-unions in the extremities (arms and legs), or patients undergoing the second stage of the Masquelet technique.
Who cannot join
- Patients with bone infection at the time of enrolment.
- Patients with bone malignant tumor(s) at the time of enrolment.
- Patients who have been treated with chemotherapy or radiotherapy within 12 months before the enrolment.
- Patients with concomitant infectious systemic diseases at the time of enrolment.
- Patients with known inflammatory systemic diseases at the time of enrolment.
- Patients with concomitant myeloproliferative disorders at the time of enrolment.
Show all 18Show fewer
- Patients currently treated with systemic immunosuppressive agents, excluding steroids.
- Patients with active autoimmune disease.
- Patients with a pre-existing calcium metabolism disorder (i.e. hypercalcemia).
- Known hyperthyroidism or autonomous thyroid adenoma.
- Patients with coagulopathy or bleeding disorders.
- Patients who are not allowed to undergo the study procedures involving imaging (X-rays, CT scan) based on Investigator's judgement.
- Patients with known or suspected allergy or hypersensitivity to the GreenBone Implant components.
- Patients who are participating or have participated in other clinical studies within the 30 days before the study enrolment.
- Patients identified by the Investigator to have intra-operative findings that may preclude conduct of study procedure.
- Patients with occurrence of major intra-operative complications that require resuscitation or deviation from the planned surgical procedure.
- Women who are pregnant or breast-feeding or who wish to become pregnant during the period of the clinical investigation and for three months later.
- Female Patients of childbearing age (less than 24 months after the last menstrual cycle) who do not use adequate contraception.
Trial locations and contacts
8 sites in 6 countries.
8 sites in 6 countries
Italy3 sites
U.O.C. Ortopedia e Traumatologia - Osp. Maggiore "C.A. Pizzardi"
Bologna, 40133
UOC di Ortopedia e Traumatologia - Ospedali Civili di Brescia
Brescia, Lombardy, 25123
Unitá Operativa di Traumatologia,Humanitas Research Hospital
Rozzano, Milano, 20089
Bosnia and Herzegovina1 site
Orthopedic and Traumatology Clinic, University Clinical Center of Republic of Srpska
Banja Luka, Republika Srpska, 78000
Israel1 site
Orthopedic Surgery Section, Division of Surgery,Rambam Health Care Campus
Haifa, 3109601
Serbia1 site
Orthopedic Surgery Section, Global Care Surgery Hospital
Novi Sad, 21000
Slovenia1 site
Clinical Department for Traumatology,University Medical Center of Ljubljana
Ljubljana, SI-1000
United Kingdom1 site
Department of Trauma and Orthopaedic Surgery, Leeds General Infirmary
Leeds, LS13EX
About this study
Official title: A Pre-market, Multi-center, International, Open-label, Single-arm Study to Evaluate the Safety and Performance of a Class III Medical Device (GreenBone Implant) for Surgical Repair of Long Bone Defects
Multi-center, international, prospective, open-label, single-arm, first-in-human clinical investigation. The Patients enrolled in this clinical investigation will undergo a scheduled surgery for the treatment of long bone defects up to 6 cm using GreenBone Implant. After the surgery, the Patients will be monitored at pre-scheduled visits up to 12 months. Adverse events, pain, quality of life and functional parameters, as well as X-ray and CT scan, will be evaluated at scheduled follow-up visits. An independent Data Safety Monitoring Board (DSMB) will review the safety reports at regular intervals and Serious Adverse Events (SAE) as soon as reported, to protect Patients participating in the study. The initial phase of the study contemplates the treatment of bone defects up to 3 cm. An adaptive interim analysis will be performed when the first 7 Patients will have completed the 6-month follow-up visit. The DSMB will review the results of the interim analysis with respect to the primary endpoint (safety), and provide one of the following recommendations to the Sponsor: a) to stop the study for unacceptable frequency and severity of adverse events or b) to continue the study up to 25 Patients recruited and to include at least 5 Patients with a longer bone defect (> 3 cm up to 6 cm).
Read the detailed description
This is a pre-market multi-centre, international, open label, single-arm, study to evaluate the safety and performance of a Class III medical device (GreenBone Implant) for the treatment of long bone defect. Bone defects can result from malformation, high-energy traumatic events, bone resection due to different pathologies such as tumors or infections, or from the treatment of complex non-unions. Current treatment of bone defects usually implies the use of bone grafts and/or biocompatible materials, to create a scaffold that bridges the defect. Autograft and Allograft are the treatments most currently used for large bone loss, but both treatments have significant disadvantages. These types of treatment carry the risk of transferring disease from animals and/or humans to the patient; there is also a risk of host local allergic reaction. Bone substitutes are devoid of the above risks and therefore they could be used alternatively to xenografts and allografts. GreenBone is a ceramic resorbable bone scaffold that has very similar structure to bone. It can be produced in large quantities, shaped easily and sterilised without losing its properties. Consequently, it is an ideal substitute that could be used to fill bone defects. This study will assess the safety of using GreenBone treatment of long bone defects up to 6 cm. Moreover it will assess its capacity of promoting new bone formation. The investigators will recruit 25 patients with long bone defect and instead of bovine xenograft we will use the GreenBone implant for the long bone reconstruction. Patients will be followed up for 12 months in total.
- Conditions
- Bone Substitutes, Bone Defect
- Being tested
- surgical repair of long bone defects
- Keywords
- Bone substitute, Bone regeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
surgical repair of long bone defectsDevice
Current treatment of bone defects usually implies the use of bone grafts and/or biocompatible materials, to create a scaffold that bridges the defect, favoring the migration of cells from the neighboring tissues to fill the gap. Autograft and Allograft are the treatments most currently used for large bone loss, but both treatments have significant disadvantages. Different types of synthetic materials have been tested for repair of long bone gaps.
However, at the moment, there is not any bone substitute with the ideal/desirable osteoinductive, osteoconductive and mechanical properties. GreenBone Implant is a synthetic, acellular, reabsorbable, new generation bone graft, being suitable for surgical reconstruction of bone defects.
| Study group | Role | What they receive |
|---|---|---|
| Surgical repair of long bone defects | Experimental | The Patients in the study group will be surgically treated and the GreenBone Bone Substitute will be implanted Receives: Device: surgical repair of long bone defects |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
Evaluation of adverse events rate during the study period.
Measured: Overall study period up to 12 months
Secondary outcomes (6)
Bone Union (Bone Healing) Evaluation Through Modified Lane and Sandhu Radiological Scoring System
Evaluation of the bone regeneration in the area of intervention in comparison to baseline (V1), by means of X-ray and/or CT scan examination, on visits V3, V4, V5, V6, V7 and V8. X-ray scoring systems have been implemented according to the criteria proposed by modified Lane and Sandhu Radiological Scoring System (Lane 1987). This scoring system evaluates bone formation and union. To evaluate the bone formation, there is a scale with 5 points, from 0 to 4 (0=No evidence of bone formation-4=Bone formation occupying 100% of defect). To evaluate bone union, there is a scale with 3 points, from 0 to 2 (0=Non-union-2=Radiographic union).
Measured: At the end of visits 1,3,4,5,6,7,8 (respectively performed at screening and 1,2,3,6,9,12 months after the surgery, each visit is 1 day)
Bone Regeneration Evaluation Through Modified Lane and Sandhu Radiological Scoring System
Evaluation of the bone regeneration in the area of intervention in comparison to baseline (V1), by means of X-ray and/or CT scan examination, on visits V3, V4, V5, V6, V7 and V8. X-ray scoring systems have been implemented according to the criteria proposed by modified Lane and Sandhu Radiological Scoring System (Lane 1987). This scoring system evaluates bone formation and union. To evaluate the bone formation, there is a scale with 5 points, from 0 to 4 (0=No evidence of bone formation-4=Bone formation occupying 100% of defect). To evaluate bone union, there is a scale with 3 points, from 0 to 2 (0=Non-union-2=Radiographic union).
Measured: At the end of visits 1,3,4,5,6,7,8 (respectively performed at screening and 1,2,3,6,9,12 months after the surgery, each visit is 1 day)
Evaluation of Pain
Evaluation of degree of pain perceived by the Patient, by means of a Visual Analogue Score (VAS/0-10 point scale), on visits V1, V3, V4, V5, V6, V7 and V8. The Visual Analogue Score (VAS) that a scale with 10 points, from 0 to 10, 0 indicates "no pain at all" and 10 the "worst pain ever".
Measured: At the end of visits 1,3,4,5,6,7,8 (respectively performed at screening and 1,2,3,6,9,12 months after the surgery, each visit is 1 day)
Evaluation of Quality-of-Life
Evaluation of Quality-of-Life by means of EuroQoL EQ-5D-5L Validated Questionnaire, on visits V1, V3, V4, V5, V6, V7 and V8. The EQ-5D-5L is a descriptive system. This system comprises the same 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems.
Measured: At the end of visits 1,3,4,5,6,7,8 (respectively performed at screening and 1,2,3,6,9,12 months after the surgery, each visit is 1 day)
Global Tolerability of Patient to Treatment
Evaluation of global tolerability to treatment of Patient (by the Investigator), through a standardized questionnaire, on visits V3, V4, V5, V6, V7 and V8. Global Tolerability Questionnaire is a questionnaire with 6 questions that are completed by the investigator in order to evaluate the operated site.
Measured: At the end of visits 3,4,5,6,7,8 (respectively performed 1,2,3,6,9,12 months after the surgery, each visit is 1 day)
Reinterventions Number
Evaluation of the number of re-interventions occurring for the Patient throughout the 12-month observation period.
Measured: between 1 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2019
- Study start22 Jan 2019
- Primary completion8 Jun 2023
- Study completion8 Jun 2023
Why it stopped: The enrolment phase was halted prematurely due to logistic issues ( SARS-CoV2 pandemic). All patients enrolled completed the follow-up visits according to the study protocol.
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.
- Other trials for Bone SubstitutesStudies 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 N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- GreenBone Ortho S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Peter Giannoudis, MD, Principal investigator, Leeds Teaching Hospital NHS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03884790
- Sponsor's protocol ID
- GB-02-18
- Status last verified
- Jun 2024
- First submitted
- 19 Mar 2019
- Last updated
- 10 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pre-market, Multi-center, International, Open-label, Single-arm Study to Evaluate the Safety and Performance of a Class III Medical Device (GreenBone Implant) for Surgical Repair of Long Bone Defects
- ClinicalTrials.gov ID
- NCT03884790
- Acronym / sponsor ID
- GB-02-18
- Conditions
- Bone Substitutes, Bone Defect
- Keywords
- Bone substitute, Bone regeneration
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The enrolment phase was halted prematurely due to logistic issues ( SARS-CoV2 pandemic). All patients enrolled completed the follow-up visits according to the study protocol.
- Enrolment
- 16 participants (actual)
- Lead sponsor
- GreenBone Ortho S.p.A.Industry (pharma, biotech, devices)
- Study start
- 22 Jan 2019 (actual)
- Primary completion
- 8 Jun 2023 (actual)
- Study completion
- 8 Jun 2023 (actual)
- First posted
- 21 Mar 2019 (actual)
- Results
- Posted 10 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multi-center, international, prospective, open-label, single-arm, first-in-human clinical investigation. The Patients enrolled in this clinical investigation will undergo a scheduled surgery for the treatment of long bone defects up to 6 cm using GreenBone Implant. After the surgery, the Patients will be monitored at pre-scheduled visits up to 12 months. Adverse events, pain, quality of life and functional parameters, as well as X-ray and CT scan, will be evaluated at scheduled follow-up visits. An independent Data Safety Monitoring Board (DSMB) will review the safety reports at regular intervals and Serious Adverse Events (SAE) as soon as reported, to protect Patients participating in the study. The initial phase of the study contemplates the treatment of bone defects up to 3 cm. An adaptive interim analysis will be performed when the first 7 Patients will have completed the 6-month follow-up visit. The DSMB will review the results of the interim analysis with respect to the primary endpoint (safety), and provide one of the following recommendations to the Sponsor: a) to stop the study for unacceptable frequency and severity of adverse events or b) to continue the study up to 25 Patients recruited and to include at least 5 Patients with a longer bone defect (> 3 cm up to 6 cm).
Detailed description
This is a pre-market multi-centre, international, open label, single-arm, study to evaluate the safety and performance of a Class III medical device (GreenBone Implant) for the treatment of long bone defect. Bone defects can result from malformation, high-energy traumatic events, bone resection due to different pathologies such as tumors or infections, or from the treatment of complex non-unions. Current treatment of bone defects usually implies the use of bone grafts and/or biocompatible materials, to create a scaffold that bridges the defect. Autograft and Allograft are the treatments most currently used for large bone loss, but both treatments have significant disadvantages. These types of treatment carry the risk of transferring disease from animals and/or humans to the patient; there is also a risk of host local allergic reaction. Bone substitutes are devoid of the above risks and therefore they could be used alternatively to xenografts and allografts. GreenBone is a ceramic resorbable bone scaffold that has very similar structure to bone. It can be produced in large quantities, shaped easily and sterilised without losing its properties. Consequently, it is an ideal substitute that could be used to fill bone defects. This study will assess the safety of using GreenBone treatment of long bone defects up to 6 cm. Moreover it will assess its capacity of promoting new bone formation. The investigators will recruit 25 patients with long bone defect and instead of bovine xenograft we will use the GreenBone implant for the long bone reconstruction. Patients will be followed up for 12 months in total.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Surgical repair of long bone defects | Experimental | Device: surgical repair of long bone defectsThe Patients in the study group will be surgically treated and the GreenBone Bone Substitute will be implanted |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female Patients.
- Patients aged ≥ 18 and ≤ 65 years old.
- Patients requiring long bone defect reconstructions up to 3 cm, resulting from high-energy traumatic events, or from the treatment of complex bone non-unions in the extremities (arms and legs), or patients undergoing the second stage of the Masquelet technique.
- Patients understanding the nature of the study and providing their informed consent to participation.
- Patients willing and able to attend the follow-up visits and procedures foreseen by study protocol.
Key exclusion criteria (18 listed)
- Patients with bone infection at the time of enrolment.
- Patients with bone malignant tumor(s) at the time of enrolment.
- Patients who have been treated with chemotherapy or radiotherapy within 12 months before the enrolment.
- Patients with concomitant infectious systemic diseases at the time of enrolment.
- Patients with known inflammatory systemic diseases at the time of enrolment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| surgical repair of long bone defectsCurrent treatment of bone defects usually implies the use of bone grafts and/or biocompatible materials, to create a scaffold that bridges the defect, favoring the migration of cells from the neighboring tissues to fill the gap. Autograft and Allograft are the treatments most currently used for large bone loss, but both treatments have significant disadvantages. Different types of synthetic materials have been tested for repair of long bone gaps. However, at the moment, there is not any bone substitute with the ideal/desirable osteoinductive, osteoconductive and mechanical properties. GreenBone Implant is a synthetic, acellular, reabsorbable, new generation bone graft, being suitable for surgical reconstruction of bone defects. | Device | Surgical repair of long bone defects |
Primary outcome
Number of Participants With Adverse Events
Time frame: Overall study period up to 12 months
Evaluation of adverse events rate during the study period.
6 secondary outcomes
Bone Union (Bone Healing) Evaluation Through Modified Lane and Sandhu Radiological Scoring System
Time frame: At the end of visits 1,3,4,5,6,7,8 (respectively performed at screening and 1,2,3,6,9,12 months after the surgery, each visit is 1 day)
Bone Regeneration Evaluation Through Modified Lane and Sandhu Radiological Scoring System
Time frame: At the end of visits 1,3,4,5,6,7,8 (respectively performed at screening and 1,2,3,6,9,12 months after the surgery, each visit is 1 day)
Evaluation of Pain
Time frame: At the end of visits 1,3,4,5,6,7,8 (respectively performed at screening and 1,2,3,6,9,12 months after the surgery, each visit is 1 day)
Evaluation of Quality-of-Life
Time frame: At the end of visits 1,3,4,5,6,7,8 (respectively performed at screening and 1,2,3,6,9,12 months after the surgery, each visit is 1 day)
Global Tolerability of Patient to Treatment
Time frame: At the end of visits 3,4,5,6,7,8 (respectively performed 1,2,3,6,9,12 months after the surgery, each visit is 1 day)
Reinterventions Number
Time frame: between 1 and 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Giannoudis, MD principal investigator
Leeds Teaching Hospital NHS
8 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing surgical repair of long bone defects in people with Bone Substitutes and Bone Defect, run by GreenBone Ortho S.p.A. at 8 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Italy, Bosnia and Herzegovina, Israel, Serbia, Slovenia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (time frame: Overall study period up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2025.