Study to Assess the Efficacy and Safety of Allogeneic Osteoblastic Cells (ALLOB®) Single Implantation in Tibial Fracture

Tibial Fracture Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04432389
• Other study ID #: 000013/BT
• Status: Recruiting
• Phase: Phase 2
• Start date: January 8, 2021
• Est. completion date: March 31, 2024

Study information

• Verified date: June 2021
• Source: Bone Therapeutics S.A
• Contact: Olivier Godeaux, MD
• Phone: +32 (0)71 121000
• Email: clinicaltrials[@]bonetherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 178
• Est. completion date: March 31, 2024
• Est. primary completion date: July 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Men and women at least 18 years of age

2. 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

3. Mechanism of injury at risk of DU/NU: fracture occurring because of a high energy impact

4. 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%)

5. 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:

1. Definitive reduction at the fracture site under investigation performed with plate, screw or external fixator

2. Subjects who did not receive a standard antibiotic prophylaxis before definitive reduction at the fracture site under investigation

3. Intra-articular tibial pilon and/or plateau fracture at the site under investigation

4. Known osteomyelitis at the fracture site under investigation

5. Bone defect post-definitive reduction greater than 1cm at least on 2 cortices at the fracture site under investigation

6. Fracture requiring vascular surgery at the site under investigation

7. Pathological fractures as judged by the Investigator, such as tumor or metabolic bone disease

8. Bifocal or multifocal fracture at the site under investigation

9. Presence of fever (defined as body temperature = 38°C) or other signs/symptoms suggestive of active infection before randomization

10. Severe brain trauma with a Glasgow Coma Scale (GCS) [3 - 8] or severe spinal cord injury with impossibility of weight-bearing

11. 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)

12. Known metabolic diseases potentially interfering with bone healing as judged by the Investigator, such as thyroid dysfunction, Paget disease or severe osteoporosis

13. Planned or history of solid organ transplantation or bone marrow transplantation

14. Known disease, including genetic disease, that may possibly need solid organ transplantation

15. Subject with renal impairment requiring dialysis or with clinically significant renal impairment defined as serum creatinine >2.0 x ULN

16. Clinically significant hepatic function impairment defined as ALT/AST levels > 3x ULN or total bilirubin levels > 2 x ULN

17. Known hematologic disease as evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet values < 100,000/ul without another explanation

18. 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

19. History of hypersensitivity to human biological material including blood and blood derived products

20. Known allergy to DMSO, dextran, gentamicin and any other aminoglycosides

21. Participation in another interventional clinical study within 3 months prior to screening

22. 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

23. Previous (within 10 years) treatment with bisphosphonates

24. Current treatment with bone morphogenic protein or any other osteo-biologic intervention at the site of the tibial fracture

Related Conditions & MeSH terms

• Fractures, Bone
• Tibial Fracture
• Tibial Fractures

Intervention

Biological:
• ALLOB
After thawing, ALLOB® is a ready-to-use product for local administration at fracture site.

Other:
• placebo
Placebo injected is a saline solution injectable grade (4 mL of 0.9% NaCl) filled in single-dose vial

Locations

Country	Name	City	State
Belgium	Tf2-Be-05	Anderlecht
Belgium	Tf2-Be-03	Genk
Belgium	Tf2-Be-04	Leuven
Belgium	Tf2-Be-01	Lodelinsart
Czechia	Tf2-Cz-01	Ceské Budejovice
Czechia	Tf2-Cz-05	Jindrichuv Hradec
Czechia	Tf2-Cz-03	Kladno
Czechia	Tf2-Cz-04	Nový Jicín
Czechia	Tf2-Cz-02	Praha
Czechia	Tf2-Cz-06	Praha
France	Tf2-Fr-04	Amiens
France	Tf2-Fr-06	Amiens
France	Tf2-Fr-01	Brest
France	Tf2-Fr-02	Chambray-lès-Tours
France	Tf2-Fr-06	Poitiers
Germany	Tf2-de-04	Gießen
Germany	Tf2-de-06	Luebeck
Germany	Tf2-de-02	Mannheim
Germany	Tf2-de-01	Münster
Hungary	Tf2-Hu-01	Budapest
Hungary	Tf2-Hu-06	Eger
Hungary	Tf2-Hu-05	Kaposvár
Hungary	Tf2-Hu-02	Pécs
Hungary	Tf2-Hu-03	Székesfehérvár
Hungary	Tf2-Hu-04	Szolnok
Poland	Tf2-Pl-12	Kielce
Poland	Tf2-Pl-08	Kraków
Poland	Tf2-Pl-02	Lódz
Poland	Tf2-Pl-01	Szczecin
Poland	Ft2-Pl-07	Warszawa
Poland	Tf2-Pl-06	Warszawa
Spain	Tf2-Es-09	Badalona
Spain	Tf2-Es-02	Barcelona
Spain	Tf2-Es-03	Barcelona
Spain	Tf2-Es-07	Barcelona
Spain	Tf2-Es-08	Barcelona
Spain	Tf2-Es-06	Málaga
Spain	Tf2-Es-05	Pontevedra
Spain	Tf2-Es-01	Terrassa

Sponsors (2)

Lead Sponsor	Collaborator
Bone Therapeutics S.A	ICON plc

Countries where clinical trial is conducted

Belgium,  Czechia,  France,  Germany,  Hungary,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 weeks
Secondary	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.	16 weeks - 20 weeks - 6 months
Secondary	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.	weeks 12 - 16 - 20 - 6 months