A pilot Phase I/IIa, multicentre, open proof-of-concept study on the efficacy and safety of allogeneic osteoblastic cells (ALLOB®) implantation in non-infected delayed-union fractures

Phase 1

• Conditions: on-infected delayed-union fractures; MedDRA version: 20.0Level: PTClassification code 10017081Term: Fracture delayed unionSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2012-005333-36-BE
• Lead Sponsor: Bone Therapeutics S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-02-25
• Last Update Posted: 10 August 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

- Patient aged 18 to 80 years inclusive
- Patient diagnosed with a non-infected delayed-union fracture of a long bone (femur, tibia, fibula, humerus, ulna, radius) of minimum 3 months and maximum 7 months (± 2 weeks) without signs of healing over the last 4 weeks at the time of screening
- Modified Radiographic Union Score (mRUS)* < 10
- Global Disease Evaluation Score as assessed by the patient = 20 mm on a Visual Analogue Scale
- Patient (or patient’s legally acceptable representative) capable to provide a written, dated, and signed informed consent prior to any study procedure.

*In case the mRUS is not assessable, the Tomographic Union Score (TUS) could be used instead (judged by the independent Reader)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

Current symptoms and/or signs related to the disease under study
- Fracture interline > 2.5 cm, as defined by the Independent Radiologist
- Insufficient reduction of the fracture
- Insufficient fracture stability defined as osteolysis at the level of the nails/screws and/or defect and/or mobility of the osteosynthesis material at physical examination, as assessed by the Investigator
- Osteosynthesis material revision or surgery (i) performed less than 2 months from the screening visit at the fracture site or (ii) performed less than 4 weeks from the screening visit at distance of the fracture site.
- Active bone infection (at site)
- Femoral neck fracture, if the femur is the target bone of the study
- Multifocal fracture (e.g., more than one fracture site on the studied bone)
- Symptomatic delayed/non-union fracture on the neighbouring bone , as judged by the Investigator
- Severe nerve damage and/or neuropathic/neuropathic-like pain at fracture site, that may interfere with assessment during the study, as appreciated by the Investigator
- Severe tendon lesion (e.g., rupture or enthesopathy) at fracture site, that may interfere with assessment during the study, as appreciated by the Investigator

Current or previous diagnoses, signs and/or symptoms
- Positive serology for HIV (defined as positive Anti-HIV 1 and/or 2 and/or positive PCR)
- Active hepatitis B (defined as positive HBs Ag and/or positive PCR)
- Active hepatitis C (defined as positive Anti-HCV and/or positive PCR)
- Global sepsis
- Renal impairment, defined as serum creatinine >2 mg/dl or 176 µmol/L
- Hepatic impairment, defined as alanine aminotransferase or aspartate aminotransferase = 3 times the upper normal limit
- Poorly controlled diabetes mellitus (defined as HbA1C >8%)
- Known allergy to gentamicin
- History of hypersensitivity to human biological material including blood and blood derived products, documented clinically or by laboratory tests
- Current or past history of solid or haematological neoplasia
- History of organ or bone marrow transplantation
- Active autoimmune disease (e.g., sclerodermia, Sjögren syndrome, lupus,...)
- Any concomitant disease that could interfere with the evaluation of efficacy, as judged by the Investigator, including but not limited to local or metabolic bone diseases
- Life expectancy less than 6 months

Current or previous treatment
- Patients who have previously been treated with ALLOB®
- Participation in another clinical study involving a pharmacological treatment within 3 months prior to screening
- Current (or within 1 month of screening) treatment with calcitonin, raloxifen, teriparatide, and/or strontium ralenate
- Current (or within 6 months of screening) illicit drug abuse (as per local law)

Safety aspects concerning female subjects of childbearing potential
- Pregnancy
- Breast-feeding
- Woman not willing or able to use a reliable contraceptive method for at
least 6 weeks prior to screening and during the whole study period.
Reliable contraceptive methods include orally administered hormonal
contraceptives, surgical intervention (e.g., tubal ligation), and
intrauterine device (IUD).
- Woman with positive urine pregnancy tests at Visits #1 and/or #2.

Other exclusion criteria
- Body Mass Index (BMI) of 35 kg/m2 or greater
- Unable to undergo general anaesthesia or a surgical intervention

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified