Study to Assess the Efficacy and Safety of Allogeneic Osteoblastic Cells (ALLOB®) Single Implantation in Tibial Fracture (ALLOB-TF2)
Primary Purpose
Tibial Fracture
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ALLOB
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Tibial Fracture
Eligibility Criteria
Inclusion Criteria:
- Men and women at least 18 years of age
- Subject diagnosed with a fresh proximal, midshaft or distal tibial fracture with definitive reduction performed with nail(s) and wound closure within 1 week of fracture occurrence
- Mechanism of injury at risk of DU/NU: fracture occurring because of a high energy impact
At increased risk of DU/NU defined by:
- Severe open fracture (Gustilo-Anderson grade IIIa and IIIb) OR
- Open (Gustilo-Anderson grade I-II) or closed (Tscherne grade II-III) fracture with at least one additional risk factor among smoking , comminuted fracture or cortical continuity (0-50%)
- Ability to obtain a written, dated, and signed informed consent prior to any study related procedures and ability to understand and comply with study requirements
Exclusion Criteria:
- Definitive reduction at the fracture site under investigation performed with plate, screw or external fixator
- Subjects who did not receive a standard antibiotic prophylaxis before definitive reduction at the fracture site under investigation
- Intra-articular tibial pilon and/or plateau fracture at the site under investigation
- Known osteomyelitis at the fracture site under investigation
- Bone defect post-definitive reduction greater than 1cm at least on 2 cortices at the fracture site under investigation
- Fracture requiring vascular surgery at the site under investigation
- Pathological fractures as judged by the Investigator, such as tumor or metabolic bone disease
- Bifocal or multifocal fracture at the site under investigation
- Presence of fever (defined as body temperature ≥ 38°C) or other signs/symptoms suggestive of active infection before randomization
- Severe brain trauma with a Glasgow Coma Scale (GCS) [3 - 8] or severe spinal cord injury with impossibility of weight-bearing
- Current or history (within 5 years) of any 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)
- Known metabolic diseases potentially interfering with bone healing as judged by the Investigator, such as thyroid dysfunction, Paget disease or severe osteoporosis
- Planned or history of solid organ transplantation or bone marrow transplantation
- Known disease, including genetic disease, that may possibly need solid organ transplantation
- Subject with renal impairment requiring dialysis or with clinically significant renal impairment defined as serum creatinine >2.0 x ULN
- Clinically significant hepatic function impairment defined as ALT/AST levels > 3x ULN or total bilirubin levels > 2 x ULN
- Known hematologic disease as evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet values < 100,000/ul without another explanation
- Subject with an history of long standing poorly controlled chronic hypertension or diabetes that could put him at risk of needing a kidney transplant later on according to the Investigator
- History of hypersensitivity to human biological material including blood and blood derived products
- Known allergy to DMSO, dextran, gentamicin and any other aminoglycosides
- Participation in another interventional clinical study within 3 months prior to screening
- Any chronic intake of medication within one month that might affect bone metabolism or the quality of bone formation such as but not limited to bisphosphonates, teriparatide, systemic steroids, anticoagulant therapies, methotrexate and other immunosuppressant drugs or related immunotherapy
- Previous (within 10 years) treatment with bisphosphonates
- Current treatment with bone morphogenic protein or any other osteo-biologic intervention at the site of the tibial fracture
Sites / Locations
- Tf2-Be-05
- Tf2-Be-03
- Tf2-Be-04
- Tf2-Be-01
- Tf2-Cz-05
- Tf2-Cz-03
- Tf2-Cz-04
- Tf2-Cz-02
- Tf2-Cz-06
- Tf2-Cz-01
- Tf2-Fr-06
- Tf2-Fr-04
- Tf2-Fr-01
- Tf2-Fr-02
- Tf2-Fr-06
- Tf2-de-04
- Tf2-de-06
- Tf2-de-02
- Tf2-de-01
- Tf2-Hu-01
- Tf2-Hu-06
- Tf2-Hu-05
- Tf2-Hu-02
- Tf2-Hu-04Recruiting
- Tf2-Hu-03Recruiting
- Tf2-Pl-12
- Tf2-Pl-08
- Tf2-Pl-01
- Ft2-Pl-07
- Tf2-Pl-06Recruiting
- Tf2-Pl-02
- Tf2-Es-09
- Tf2-Es-08
- Tf2-Es-02Recruiting
- Tf2-Es-03
- Tf2-Es-07
- Tf2-Es-06
- Tf2-Es-05
- Tf2-Es-01
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ALLOB
placebo
Arm Description
Single injection of ALLOB at fracture site (4 ml)
Single injection of Placebo at fracture site (4 ml)
Outcomes
Primary Outcome Measures
proportion of subjects with a radiological success at Week 12
A radiological success is defined as a subject with a Radiological Union Score for Tibia (RUST) above the threshold value predictive of a normal bone healing.
Secondary Outcome Measures
Proportion of subjects with radiological success at Week 16, Week 20 and Month 6
A radiological success is defined as a subject with a Radiological Union Score for Tibia (RUST) above the threshold value predictive of a normal bone healing.
Change in Radiographic Union Score for Tibia (RUST) at Week 12, Week 16, Week 20 and Month 6 compared to baseline visit
Radiological fracture healing is defined by a radiological fracture union evaluated and adjudicated by Independent Radiologists.
Full Information
NCT ID
NCT04432389
First Posted
June 9, 2020
Last Updated
June 4, 2021
Sponsor
Bone Therapeutics S.A
Collaborators
ICON plc
1. Study Identification
Unique Protocol Identification Number
NCT04432389
Brief Title
Study to Assess the Efficacy and Safety of Allogeneic Osteoblastic Cells (ALLOB®) Single Implantation in Tibial Fracture
Acronym
ALLOB-TF2
Official Title
Phase IIb, Placebo-Controlled, Randomized, Double-Blind, Multicenter Study to Assess the Efficacy and Safety of Allogeneic Osteoblastic Cells (ALLOB®) Single Implantation in Tibial Fracture
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Recruiting
Study Start Date
January 8, 2021 (Actual)
Primary Completion Date
July 31, 2022 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bone Therapeutics S.A
Collaborators
ICON plc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Although the majority of tibial fractures heal normally, some fractures may not heal within the usual time frame and is known as delayed bone healing within 4 to 6 months and absence of bone healing within 9 to 12 months in the most severe case of. Several factors can increase the risks of delayed healing complications like, for example, smoking, violent shocks (for example, due to a road accident) or even the type of fracture (an open fracture). The location of the fracture is also an important factor: among the bones of the arms and legs, the tibia is known for being the most at risk for complications. At tibial fracture with several risk factors could lead to delayed complications and interfere with patient daily life and reduce the quality of life.
The study drug, ALLOB®, is constituted of bone cells produced from the bone marrow of healthy adult donors. Preclinical studies have shown that ALLOB® cells are capable of forming bone and repairing fractures. When directly injected into a fracture, ALLOB® should therefore promote the healing of the fracture by re-establishing a healthy environment and stimulating bone production. To date, there is no treatment for fractures considered at risk of delayed complications. The current practice on diagnosis of complications is to wait at least 6-12 months before considering alternative interventions to promote fracture healing. The injection of ALLOB® quickly after the fracture should stimulate bone healing, reduce healing time, reduce complications, and improve the quality of life for the patient. ALLOB® has already shown preliminary evidence of effectiveness in the treatment of delayed bone healing fractures (ALLOB-DU1 clinical trial), including tibial fractures (8 patients). With this study, the Sponsor will evaluate whether ALLOB® promotes the healing of tibial fractures compared with placebo.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tibial Fracture
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
178 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ALLOB
Arm Type
Experimental
Arm Description
Single injection of ALLOB at fracture site (4 ml)
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Single injection of Placebo at fracture site (4 ml)
Intervention Type
Biological
Intervention Name(s)
ALLOB
Intervention Description
After thawing, ALLOB® is a ready-to-use product for local administration at fracture site.
Intervention Type
Other
Intervention Name(s)
placebo
Intervention Description
Placebo injected is a saline solution injectable grade (4 mL of 0.9% NaCl) filled in single-dose vial
Primary Outcome Measure Information:
Title
proportion of subjects with a radiological success at Week 12
Description
A radiological success is defined as a subject with a Radiological Union Score for Tibia (RUST) above the threshold value predictive of a normal bone healing.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Proportion of subjects with radiological success at Week 16, Week 20 and Month 6
Description
A radiological success is defined as a subject with a Radiological Union Score for Tibia (RUST) above the threshold value predictive of a normal bone healing.
Time Frame
16 weeks - 20 weeks - 6 months
Title
Change in Radiographic Union Score for Tibia (RUST) at Week 12, Week 16, Week 20 and Month 6 compared to baseline visit
Description
Radiological fracture healing is defined by a radiological fracture union evaluated and adjudicated by Independent Radiologists.
Time Frame
weeks 12 - 16 - 20 - 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Men and women at least 18 years of age
Subject diagnosed with a fresh proximal, midshaft or distal tibial fracture with definitive reduction performed with nail(s) and wound closure within 1 week of fracture occurrence
Mechanism of injury at risk of DU/NU: fracture occurring because of a high energy impact
At increased risk of DU/NU defined by:
Severe open fracture (Gustilo-Anderson grade IIIa and IIIb) OR
Open (Gustilo-Anderson grade I-II) or closed (Tscherne grade II-III) fracture with at least one additional risk factor among smoking , comminuted fracture or cortical continuity (0-50%)
Ability to obtain a written, dated, and signed informed consent prior to any study related procedures and ability to understand and comply with study requirements
Exclusion Criteria:
Definitive reduction at the fracture site under investigation performed with plate, screw or external fixator
Subjects who did not receive a standard antibiotic prophylaxis before definitive reduction at the fracture site under investigation
Intra-articular tibial pilon and/or plateau fracture at the site under investigation
Known osteomyelitis at the fracture site under investigation
Bone defect post-definitive reduction greater than 1cm at least on 2 cortices at the fracture site under investigation
Fracture requiring vascular surgery at the site under investigation
Pathological fractures as judged by the Investigator, such as tumor or metabolic bone disease
Bifocal or multifocal fracture at the site under investigation
Presence of fever (defined as body temperature ≥ 38°C) or other signs/symptoms suggestive of active infection before randomization
Severe brain trauma with a Glasgow Coma Scale (GCS) [3 - 8] or severe spinal cord injury with impossibility of weight-bearing
Current or history (within 5 years) of any 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)
Known metabolic diseases potentially interfering with bone healing as judged by the Investigator, such as thyroid dysfunction, Paget disease or severe osteoporosis
Planned or history of solid organ transplantation or bone marrow transplantation
Known disease, including genetic disease, that may possibly need solid organ transplantation
Subject with renal impairment requiring dialysis or with clinically significant renal impairment defined as serum creatinine >2.0 x ULN
Clinically significant hepatic function impairment defined as ALT/AST levels > 3x ULN or total bilirubin levels > 2 x ULN
Known hematologic disease as evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet values < 100,000/ul without another explanation
Subject with an history of long standing poorly controlled chronic hypertension or diabetes that could put him at risk of needing a kidney transplant later on according to the Investigator
History of hypersensitivity to human biological material including blood and blood derived products
Known allergy to DMSO, dextran, gentamicin and any other aminoglycosides
Participation in another interventional clinical study within 3 months prior to screening
Any chronic intake of medication within one month that might affect bone metabolism or the quality of bone formation such as but not limited to bisphosphonates, teriparatide, systemic steroids, anticoagulant therapies, methotrexate and other immunosuppressant drugs or related immunotherapy
Previous (within 10 years) treatment with bisphosphonates
Current treatment with bone morphogenic protein or any other osteo-biologic intervention at the site of the tibial fracture
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Olivier Godeaux, MD
Phone
+32 (0)71 121000
Email
clinicaltrials@bonetherapeutics.com
Facility Information:
Facility Name
Tf2-Be-05
City
Anderlecht
ZIP/Postal Code
1070
Country
Belgium
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Be-03
City
Genk
ZIP/Postal Code
3600
Country
Belgium
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Be-04
City
Leuven
Country
Belgium
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Be-01
City
Lodelinsart
Country
Belgium
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Facility Name
Tf2-Cz-05
City
Jindřichův Hradec
Country
Czechia
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Cz-03
City
Kladno
Country
Czechia
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Cz-04
City
Nový Jičín
Country
Czechia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Facility Name
Tf2-Cz-02
City
Praha
Country
Czechia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Facility Name
Tf2-Cz-06
City
Praha
Country
Czechia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Facility Name
Tf2-Cz-01
City
České Budějovice
Country
Czechia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Facility Name
Tf2-Fr-06
City
Amiens
ZIP/Postal Code
80000
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
study coordinator
Facility Name
Tf2-Fr-04
City
Amiens
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Fr-01
City
Brest
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Fr-02
City
Chambray-lès-Tours
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Fr-06
City
Poitiers
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Tf2-de-04
City
Gießen
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Facility Name
Tf2-de-06
City
Luebeck
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Facility Name
Tf2-de-02
City
Mannheim
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Tf2-de-01
City
Münster
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Facility Name
Tf2-Hu-01
City
Budapest
Country
Hungary
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study coordinator
Facility Name
Tf2-Hu-06
City
Eger
ZIP/Postal Code
3300
Country
Hungary
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Hu-05
City
Kaposvár
Country
Hungary
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Hu-02
City
Pécs
Country
Hungary
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Hu-04
City
Szolnok
Country
Hungary
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study coordinator
Facility Name
Tf2-Hu-03
City
Székesfehérvár
Country
Hungary
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Facility Name
Tf2-Pl-12
City
Kielce
Country
Poland
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Pl-08
City
Kraków
Country
Poland
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Pl-01
City
Szczecin
Country
Poland
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Facility Name
Ft2-Pl-07
City
Warszawa
Country
Poland
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Pl-06
City
Warszawa
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study coordinator
Facility Name
Tf2-Pl-02
City
Łódź
Country
Poland
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Es-09
City
Badalona
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Es-08
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Es-02
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Facility Name
Tf2-Es-03
City
Barcelona
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Es-07
City
Barcelona
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Es-06
City
Málaga
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Es-05
City
Pontevedra
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Tf2-Es-01
City
Terrassa
Country
Spain
Individual Site Status
Active, not recruiting
12. IPD Sharing Statement
Learn more about this trial
Study to Assess the Efficacy and Safety of Allogeneic Osteoblastic Cells (ALLOB®) Single Implantation in Tibial Fracture
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