Clinical trial NCT06335394: Prospective Study in Adults Evaluating Safety & Efficacy of NVD003 for Bone Reconstruction to Treat Lower Limb Nonunion
Official title: A Prospective Multicentre Single-arm Study in Adults to Evaluate the Safety and Preliminary Efficacy of the Autologous 3D Osteogenic Implant NVD-003 for Bone Reconstruction for the Treatment of Recalcitrant Lower Limb Nonunion
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Recalcitrant Lower Limb Nonunion
Lead sponsor: Novadip Biosciences
Sponsor class: INDUSTRY
First posted: 2024-03-28
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to evaluate the safety and preliminary efficacy of the autologous 3D osteogenic implant NVD-003 for bone reconstruction for the treatment of recalcitrant lower limb nonunion.

Detailed description: This is a first in man study conducted as a prospective, single-arm, non-randomized clinical study. A sample of 5 to 10 patients will be enrolled in the study in order to assess the safety of the use of NVD-003 bone graft implantation in patients with recalcitrant lower limb nonunion.

The sample size of 5 to 10 patients was considered sufficient to give a preliminary indication on the safety of the ATMP.

Eligibility criteria: Inclusion Criteria:

1. Male or female adult subject (≥18 years).
2. Radiographic images not older than 3 months, confirming lower limb nonunion, defined as the absence of clinical and radiographic progression towards healing over 3 consecutive months on serial radiographs and minimum 9 months after the first attempt of surgical bone repair, or minimum 6 months after the second (or any subsequent) attempt of surgical bone repair.
3. Radiologic single, meta- and/or diaphyseal bone defect with a maximum size of 4 cm (in case of a void that does not transverse the whole width of the bone, the total volume cannot exceed the volume corresponding to the 4 cm gap).
4. The impaired limb is salvageable, and the patient is eligible for the intended surgical procedure according to the standard hospital practice.
5. Documented normal or low bone density: Bone density scan determined by Dual Energy X-Ray Absorptiometry DEXA scan on lumbar spine and hip (bone mineral density T-scores above -2.5). An examination ≤ 1-year-old before screening is acceptable.
6. The subject is, in the Investigator's opinion, psychosocially, mentally, and physically able to fully comply with this protocol, including the postoperative regimen and follow-up visits.
7. Use of an effective birth control method for 2 months prior to the date of the intended surgical intervention up to Visit V7 for women of childbearing potential.
8. Negative urinary pregnancy test for women of childbearing potential.
9. At screening, safety local laboratory test results are medically acceptable to undergo surgery (see Section 7.3.2) and serology results are in accordance with country specific requirements for donation of Human Body Material.
10. At time of adipose tissue collection, central laboratory serology and molecular tests panel for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and syphilis are in accordance with Belgian specific requirements for release of Human Body Material.
11. The subject has understood the nature of the study, agrees to its provisions, and has accepted to participate in the study and to follow all study procedures. This is acknowledged by signing the informed consent as approved by the required Institutional Review Board/Ethics Committee and the national competent authorities.
12. Patient fulfils the criteria to donate his human body material (adipose tissue) and is suitable to undergo a liposuction.

Exclusion Criteria:

1. The subject has a Body Mass Index (BMI) ≤ 20 kg/m² or ≥ 40 kg/m², or of ≥35 kg/m² with obesity-related health conditions, such as high blood pressure or diabetes.
2. Multifocal or comminuted fractures.
3. A planned use of an external fixator is not allowed as of the grafting surgery (V1) until V7.
4. Documented osteoporosis: bone density determined using DEXA scan on lumbar spine and hip: bone mineral density T-scores of -2.5 and below. An examination ≤ 1-year-old before screening is acceptable.
5. Pregnant or breast-feeding woman.
6. The subject shows signs of an active drug or alcohol dependence, serious current illness, mental illness or any other factors which, in the opinion of the investigator, will interfere with study conduct or the interpretation of the results.
7. The patient has a history of solid organ transplant at any point in the past or is on the waiting list for future organ transplantation.
8. The subject previously received a cellular therapy treatment at any point in time (as per protocol description).
9. Previous exposure to any experimental therapy with another investigational drug within 60 days prior to screening or enrolment in any concurrent study that may confound the results of this study.
10. Any signs or suspicion of an active local (area of the future surgical site), or systemic infection before the induced membrane surgery or the grafting surgery.
11. Known allergy to any antibiotics commonly used to treat Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus) or coagulase-negative staphylococci.
12. Diagnosis of HIV, HBV (HBsAg or PCR positive), HCV, Human T-cell Lymphotropic Virus (HTLV) 1 or 2, or syphilis infection (as confirmed by serology and nucleic acid test (NAT) by Tissue Establishment).
13. Chronic use of immunosuppressive therapy (immunosuppressant/ immunotherapy) due to inflammatory or systemic disease.
14. Any clinically relevant chronic disease associated with renal or hepatic insufficiency or any chronic disease of such severity that surgery could be detrimental to the survival of the patient.
15. Subjects with poorly controlled diabetes mellitus type 2 as assessed by glycated haemoglobin (HbA1C) ≥ 10%.
16. Subjects with poorly controlled thyroid diseases (unstable despite proper medication).
17. Subjects with documented metabolic bone disease (based on the investigator judgment) such as, but not limited to, osteogenesis imperfecta or osteomalacia.
18. Chronic, current or planned during study use of any medications that might affect bone metabolism or the quality of bone formation such as, but not limited to, bisphosphonates, steroids, methotrexate, anticoagulant therapies, immunosuppressant therapy or immunotherapy. However, short lasting surgery-related prophylactic treatments such as antibiotics, analgesics and low molecular heparin drugs may be administered according to hospital recommendations.
19. Existing malignant tumour in the vicinity of the graft or a resected one not cured for more than 5 years.
20. Any other illness which might reduce life expectancy to less than 2 years from screening.
21. The subject is a prisoner.

Primary outcomes:
measure: Safety - Adverse Events
timeFrame: From graft implantation until completion of visit 24 months
measure: Safety - Abnormalities of vital signs
timeFrame: At hospital discharge (1-2 weeks after grafting surgery), at visit 1,5 months, at visit 3 months, at visit 6 months, at visit 12 months and visit 24 months
measure: Safety - Abnormalities of vital signs
timeFrame: At hospital discharge (1-2 weeks after grafting surgery), at visit 1,5 months, at visit 3 months, at visit 6 months, at visit 12 months and visit 24 months
measure: Safety - Abnormalities of physical examination
timeFrame: At hospital discharge (1-2 weeks after grafting surgery), at visit 1,5 months, at visit 3 months, at visit 6 months, at visit 12 months and visit 24 months
measure: Safety - Abnormalities of physical examination
timeFrame: At hospital discharge (1-2 weeks after grafting surgery), at visit 1,5 months, at visit 3 months, at visit 6 months, at visit 12 months and visit 24 months
measure: Safety - Abnormalities of physical examination
timeFrame: At hospital discharge (1-2 weeks after grafting surgery), at visit 1,5 months, at visit 3 months, at visit 6 months, at visit 12 months and visit 24 months
measure: Safety - Abnormalities of laboratories
timeFrame: At hospital discharge (1-2 weeks after grafting surgery), at visit 1,5 months, at visit 3 months, at visit 6 months, at visit 12 months and visit 24 months
measure: Safety - Abnormalities of laboratories
timeFrame: At hospital discharge (1-2 weeks after grafting surgery), at visit 1,5 months, at visit 3 months, at visit 6 months, at visit 12 months and visit 24 months
measure: Safety - Abnormalities of laboratories
timeFrame: At hospital discharge (1-2 weeks after grafting surgery), at visit 1,5 months, at visit 3 months, at visit 6 months, at visit 12 months and visit 24 months
Secondary outcomes:
measure: Healing efficacy: plain X-ray
timeFrame: At 6 weeks, 3 months, 6 months, 12 months, at additional visits (if no healing at 12 months after graft implant surgery) up to 24 months.
measure: Healing efficacy: CT-scan
timeFrame: At 6, 12 and 24 months
measure: Healing efficacy: average time from Investigational Medicinal Product grafting surgery till first observation of plain X-ray and CT-scan confirmed fracture healing
timeFrame: Average time from IMP grafting surgery till first observation of plain X-ray and CT-scan up to 24 months
measure: Healing efficacy: investigator assessed clinical healing
timeFrame: From 6 weeks post-grafting onwards up to 24 months
measure: Healing efficacy: average time from IMP grafting surgery to Investigator assessed clinical healing
timeFrame: Time from grafting surgery till first observation of investigator assessed clinical healing up to 24 months
measure: Grafting Surgery parameters
timeFrame: Duration of grafting surgery (visit 1) and duration of hospitalization after grafting surgery (visit 2)
measure: Grafting Surgery parameters
timeFrame: Duration of grafting surgery (visit 1) and duration of hospitalization after grafting surgery (visit 2)
measure: Complications: rate of subsequent surgical interventions
timeFrame: At 12 and 24 months post-implant surgery
measure: Quality of Life: pain evaluation
timeFrame: At screening and at 6 weeks, 3, 6, 12 and 24 months post-graft
measure: Quality of Life: questionnaire EuroQol-5 Dimensions
timeFrame: At screening and at 6 weeks, 3, 6, 12 and 24 months post-graft
measure: Quality of Life: overall treatment effect
timeFrame: At 3, 6, 12 and 24 months post-graft
measure: General Pre-graft implantation safety: all SAEs, AESI and PRAE
timeFrame: Pre-graft implantation
measure: All SAEs during the extended safety follow-up period
timeFrame: During the extended safety follow-up period (between 24 months FU visit and 5 years post-grafting surgery)
Other outcomes:
Locations:
city: Anderlecht
country: Belgium
facility: Centre Hospitalier Interregional Edith Cavel (CHIREC) - Clinique Ste Anne-St Remi
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis (AZ) Sint-Jan Brugge - Oostende AV - Campus Sint-Jan
city: Brussel
country: Belgium
facility: Centre Hospitalier Universitaire CHU/UVC Brugmann (Site Horta)
city: Charleroi
country: Belgium
facility: Grand Hôpital De Charleroi
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg (ZOL)
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven, Campus Gasthuisberg
city: Mons
country: Belgium
facility: CHU Ambroise Paré
city: Namur
country: Belgium
facility: Centre Hospitalier Regional De Namur
city: Luxembourg
country: Luxembourg
facility: Centre Hospitalier de Luxembourg
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: CHU Ambroise Paré
name: Christophe Marchal, MD
role: PRINCIPAL_INVESTIGATOR
References: