Prospective Study in Adults Evaluating Safety & Efficacy of NVD003 for Bone Reconstruction to Treat Lower Limb Nonunion

NCT06335394 | Active Not Recruiting Phase 1

• 1 other identifier: NVD003-CLN01
• Study Type: interventional
• Target: 11
• Locations: 3 countries
• Sites: 10

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.

Conditions

Recalcitrant Lower Limb Nonunion

Outcome Measures

Primary Outcomes (9)

• Safety - Adverse Events

  All Adverse Events (AEs) including Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESI) and Procedure Related AE's (PRAE).

  From graft implantation until completion of visit 24 months

• Safety - Abnormalities of vital signs

  Vital signs abnormalities: blood pressure

  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

• Safety - Abnormalities of vital signs

  Vital signs abnormalities: heart rate

  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

• Safety - Abnormalities of physical examination

  Physical examinations abnormalities: cardiovascular system

  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

• Safety - Abnormalities of physical examination

  Physical examinations abnormalities: respiratory system

  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

• Safety - Abnormalities of physical examination

  Physical examinations abnormalities: legs examination (inspection of both legs and extensive examination of the affected leg)

  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

• Safety - Abnormalities of laboratories

  Safety laboratories abnormalities: blood sampling: haematology (tests that yield information on the qualitative and quantitative composition of the cellular components of the blood)

  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

• Safety - Abnormalities of laboratories

  Safety laboratories abnormalities: blood sampling: coagulation (measure your blood's ability to clot, and how long it takes to clot)

  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

• Safety - Abnormalities of laboratories

  Safety laboratories abnormalities: blood sampling: biochemistry (tests to evaluate organ function, electrolyte status, hormone levels and more (calcium, vitamin D))

  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 (13)

• Healing efficacy: plain X-ray

  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.

• Healing efficacy: CT-scan

  At 6, 12 and 24 months

• Healing efficacy: average time from Investigational Medicinal Product grafting surgery till first observation of plain X-ray and CT-scan confirmed fracture healing

  Average time from IMP grafting surgery till first observation of plain X-ray and CT-scan up to 24 months

• Healing efficacy: investigator assessed clinical healing

  From 6 weeks post-grafting onwards up to 24 months

• Healing efficacy: average time from IMP grafting surgery to Investigator assessed clinical healing

  Time from grafting surgery till first observation of investigator assessed clinical healing up to 24 months

Study Arms (1)

Single-arm study

EXPERIMENTAL

NVD003

Other: NVD003

Interventions

NVD003 OTHER

Autologous osteogenic implant NVD-003 for bone reconstruction

Single-arm study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female adult subject (≥18 years).
• 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.
• 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).
• The impaired limb is salvageable, and the patient is eligible for the intended surgical procedure according to the standard hospital practice.
• 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.
• 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.
• 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.
• Negative urinary pregnancy test for women of childbearing potential.
• 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.
• 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.
• 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.
• Patient fulfils the criteria to donate his human body material (adipose tissue) and is suitable to undergo a liposuction.

You may not qualify if:

• 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.
• Multifocal or comminuted fractures.
• A planned use of an external fixator is not allowed as of the grafting surgery (V1) until V7.
• 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.
• Pregnant or breast-feeding woman.
• 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.
• 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.
• The subject previously received a cellular therapy treatment at any point in time (as per protocol description).
• 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.
• 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.
• Known allergy to any antibiotics commonly used to treat Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus) or coagulase-negative staphylococci.
• 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).
• Chronic use of immunosuppressive therapy (immunosuppressant/ immunotherapy) due to inflammatory or systemic disease.
• 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.
• Subjects with poorly controlled diabetes mellitus type 2 as assessed by glycated haemoglobin (HbA1C) ≥ 10%.

Sponsors & Collaborators

• Novadip Biosciences: lead

Study Sites (10)

Centre Hospitalier Interregional Edith Cavel (CHIREC) - Clinique Ste Anne-St Remi

Anderlecht, 1070, Belgium

Location

Algemeen Ziekenhuis (AZ) Sint-Jan Brugge - Oostende AV - Campus Sint-Jan

Bruges, 8000, Belgium

Location

Centre Hospitalier Universitaire CHU/UVC Brugmann (Site Horta)

Brussels, 1020, Belgium

Location

Grand Hôpital De Charleroi

Charleroi, Belgium

Location

Ziekenhuis Oost-Limburg (ZOL)

Genk, 3600, Belgium

Location

Universitair Ziekenhuis Leuven, Campus Gasthuisberg

Leuven, 3000, Belgium

Location

CHU Ambroise Paré

Mons, 7000, Belgium

Location

Centre Hospitalier Regional De Namur

Namur, 5000, Belgium

Location

Centre Hospitalier de Luxembourg

Luxembourg, 1210, Luxembourg

Location

University Hospital Basel

Basel, Switzerland

Location

Study Officials

• Christophe Marchal, MD

  CHU Ambroise Paré

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2023
• First Posted: March 28, 2024
• Study Start: August 2, 2018
• Primary Completion: April 27, 2022
• Study Completion (Estimated): May 15, 2028
• Last Updated: March 28, 2024

Record last verified: 2024-03

Locations

LU (1); BE (8); CH (1)