The treatment of non-union of the tibia MedDRA version: 20.0 Level: SOC Classification code 10042613 Term: Surgical and medical procedures System Organ Class: 10042613 - Surgical and medical procedures MedDRA version: 21.0 Level: PT Classification code 10017088 Term: Fracture nonunion System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: Osteogrow-C
Product Code: rhBMP6
Pharmaceutical Form: Powder and solvent for implantation paste
INN or Proposed INN: Not yet available
Current Sponsor code: rhBMP6
Other descriptive name
Sponsors
Genera Research Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients meeting ALL of the following criteria at screening will be eligible for participation in the study: 1. Willing and able to provide informed consent and to comply with study requirements. Written informed consent must be obtained before any study assessments are done. Patients must be fluent in the language that is spoken by the investigator and the trial staff and in which the informed consent is written. 2. Skeletally mature male or female, age =18 years. Females of childbearing potential must use a highly effective method of birth control within 1 year following surgery, be willing to extend the use for additional year, if needed, and must have a negative urine pregnancy test prior to randomization. 3. The diagnosis of tibial non-union as a consequence of traumatic, unilateral, displaced, isolated, closed extra-articular fracture of the tibia previously treated with osteosynthetic device, confirmed by medical history and radiographic analyses. A patient is non-responsive to conservative and/or alternative treatment (e.g., electrical stimulation, ultrasound, skeletal fixation with or without supplemental bone graft), and there is a lack of evidence of healing progression over previous 3 months. 4. Otherwise in good general condition in the investigator's opinion, based on vital signs, full physical examination, standard clinical laboratory tests, ECG findings at screening. 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 28 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: Patients meeting ANY of the following criteria at screening will NOT be eligible for participation in the study: 1. Documented titanium allergy or intolerance. 2. History of bilateral bone graft harvesting from the iliac crest. 3. Previous treatment with bone morphogenetic proteins (e.g., INDUCTOS/INFUSE or OSIGRAFT/OPGENRA/OP-1). 4. Active systemic infection. 5. Presence of neuropathy, which in the investigator’s opinion can interfere with walking or appreciation of pain. 6. Presence or history of pathological fractures or osteomalacia. 7. Known active malignancy, history of malignancy (except for fully resected basal cell carcinoma of the skin), or ongoing treatment with antineoplastic agents or radiation therapy. 8. Presence of poorly controlled diabetes mellitus as evident from hemoglobin A1c >8% at screening. 9. History of autoimmune disease of connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome), or other chronic disease or condition treated with immunosuppressants. 10. History of severe symptomatic osteoarthritis or other chronic disease or condition associated with frequent or prolonged use of nonsteroidal anti-inflammatory drugs (NSAIDs). 11. History of alcohol or drug dependence, or a positive urine drug screen at screening which cannot be explained by medication history and current smokers unless they are willing to quit smoking during the six months period following surgery. 12. Treatment with platelet aggregation inhibitors within 5 days (for clopidogrel) or 7 days (for low-dose acetylsalicylic acid) prior to surgery. 13. Treatment with systemic corticosteroids within 1 week, or with immunosuppressants (e.g., methotrexate) within 2 weeks prior to surgery. 14. Treatment with an investigational drug within 6 months or 5 half-lives of the drug (whichever is longer) prior to surgery. 15. Presence of any other disease or condition which in the investigator’s opinion represents a high safety risk for surgery, or interferes with patient’s ability to comply with study procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The incidence of clinical success at 9 months after surgery, where clinical success is defined as: oFull weight-bearing on the treated leg, or ability to walk using one crutch at most, with oLess than severe pain on weight-bearing, and oNo additional surgical procedure related to the non-union. Safety endpoints: • The incidence and type of treatment-emergent adverse events (TEAEs), where TEAE is defined as any AE occurring after the start of surgery. •Change from baseline in hematology, clinical chemistry and urinalysis findings on postoperative Day 3 and 1 month after surgery. •Change from baseline in vital signs on postoperative Day 3, at discharge from the hospital, and at each onsite follow-up visit. •Change from baseline in physical examination findings at discharge from the hospital and at each onsite follow-up visit. •Change from baseline in ECG findings on postoperative Day 3. •The occurrence of anti-rhBMP6 antibodies at baseline and 3, 6, 9 and 12 months after surgery. •The incidence of heterotopic ossification at 3, 6, 9 and 12 months after surgery. •The incidence of local signs of inflammation at the non-union site (erythema, oedema, tenderness, wound discharge) over time, based on the blinded evaluator’s assessment using a 4-grade scale ranging from 0 (absent) to 3 (severe). •Change from baseline in knee and ankle range of motion (ROM) at 1, 3, 6, 9 and 12 months after surgery. •Intraoperative blood loss, estimated using a modified Lopez-Pikado’s formula. Tolerability endpoints: •The incidence of implant-related TEAEs of severe intensity. •Pain intensity in the area of iliac crests over time, assessed by the patient using a NRS. ;Timepoint(s) of evaluation of this end point: Patients will be evaluated preoperatively (within 1 months of surgery), intra-operatively, and postoperatively at 1, 2, 3, 6, 9 and 12 months. The incidence of clinical success will be evaluated at month 6, 9 and 12 months after the surgery. Complications | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The incidence of clinical success at 6 and 12 months after surgery. • Walking ability at baseline and 2, 3, 6, 9 and 12 months after surgery, based on the patient’s response to Question 6 of the American Academy of Orthopedic Surgeons Lower Limb Outcomes Questionnaire (AAOS-LLQ). • Weight-bearing at baseline and 1, 3, 6, 9 and 12 months after surgery, expressed as a percentage of body weight. • Pain intensity in the treated leg over time, at rest and on weight-bearing/walking, assessed by the patient using a numeric rating scale (NRS). • The incidence of radiographic union of the tibia at 3, 6, 9 and 12 months after surgery, based on each of the following definitions: o Cortical bridging (continuous bony connection of the non-union gap) on at least 3 out of 4 cortices on anteroposterior (AP) and latero-lateral (LL) projections; o Cortical bridging on at least 6 out of 8 cortices on AP, LL and two oblique projections; o Cortical bridging visible on at least 1 out of 4 projections (AP, LL and two oblique). • AAOS-LLQ score at baseline and 2, 3, 6, 9 and 12 months after surgery. ;Timepoint(s) of evaluation of this end point: Patients will be evaluated preoperatively (within 1 months of surgery), intra-operatively, and postoperatively at 1, 2, 3, 6, 9 and 12 months. The incidence of clinical success will be evaluated at month 6, 9 and 12 months after the surgery. Complications and adverse events will be evaluated over the course of the clinical trial. The protocol also includes plasma measurements of antibodies to rhBMP6 screening in both investigational and control patients pre-operatively and at 3, 6, 9 and 12 months. At each evaluation time-point, the primary and secondary clinical and radiographic outcome parameters will be assessed. Success will be determined from data collected during the initial 12 months of follow-up. | — |
Countries
Austria
Contacts
Public ContactClinical Trial Information
Proqlea d.o.o
Outcome results
None listed