A proof of concept study with NVD-003, an autologous osteogenic bone graft, in the treatment of congenital pseudarthrosis of the tibia in pediatric patients.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novadip Biosciences

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

28 Nov 2022 → 19 Mar 2026

Decision date (initial)

2024-07-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-515478-29-00

EudraCT number

2022-001282-12

ClinicalTrials.gov

NCT05693558

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Safety: to locally assess clinical and radiological safety: assess short, mid long and long-term safety of the NVD-003 treatment (including the adipose tissue collection procedure and the NVD-003 grafting surgery)

Secondary objectives 2

1. To centrally assess NVD 003 efficacy radiologically (bone formation, union and remodeling)
2. To locally assess NVD 003 efficacy clinically

Conditions and MedDRA coding

Congenital pseudarthrosis of the tibia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male or female pediatric patients: a. Diagnosed with congenital pseudarthrosis of the tibia (with or without NF1) and presenting with a non-healing Paley type 3 or 4 fracture. b. With a minimum weight of 5kg/11lbs. c. Within the age range of 2 years to 8 years.
2. Maximum 2 previous failed surgical orthopedic interventions to treat the primary CPT fracture.
3. Patient fulfills criteria for undergoing a surgical intervention (ATC and GS) as per standard of care.
4. Patient has serology and molecular test results excluding the presence of Human T-cell lymphoma virus (HTLV1/2), human immunodeficiency virus (HIV 1/2), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis
5. Possibility to obtain a minimum of 2cc/ 0.07fl.oz. (preferably up to 10cc/ 0.34fl oz) of adipose tissue.
6. Satisfactory general health condition to undergo surgeries (ATC and GS) with anesthesia as per local standards.
7. The fracture and patient baseline characteristics allow the application of a pre-defined standardized surgical procedure as detailed in the study specific procedures section 6.1.1.4.
8. A NVD 003 graft volume need not exceeding 20cc (0.68fl oz), confirmed by the treating orthopedic surgeon based on radiological measurements. The estimated volume should cover the total of the residual tibial bone defect volume of 0.5 to 1cm (0.2 0.39in) in height, the cross-union tibial bone-fibula volume and the eventual fibular bone defect volume.
9. The patient’s parent(s) and/or legal guardian(s) provided written informed consent and accepted the participation of the patient in the trial.

Exclusion criteria 15

1. Bilateral CPT.
2. Presence of CPT without a fracture of the tibia (Paley type 1 and 2).
3. More than 2 failed surgical attempt(s) to treat the primary tibial fracture.
4. Evidence of plexiform neurofibroma of any size or nodular fibroma ≥ 1.2in/3cm on the ipsilateral leg.
5. Clinically significant infection at the target grafting site or systemic infection.
6. History of allergic reaction or any anticipated hypersensitivity to any anesthetic agent or any potential hypersensitivity to any of the components of the NVD-003 graft (including the CMRL1066 transport medium).
7. CPT fracture requiring the use of one of the following surgical techniques: a. An external fixation system (e.g. Ilizarov, TSF, rail, …); b. A carrier or scaffold; c. An autogenous recombinant human bone morphogenetic protein.
8. Presence of clinically significant hematologic, renal, hepatic, and coagulation laboratory abnormalities (i.e., CBC, PT/INR, Chem-7, and LFTs, etc.).
9. Presence of any auto-immune disease, with exception of well controlled diabetes type 1 or auto-immune thyroid disorders.
10. Any history of experimental therapy with another investigational drug within 60 days prior to screening.
11. Presence of active tumor.
12. Documented metabolic bone disease or any disorder, such as but not limited to osteogenesis imperfecta and osteomalacia, that could interfere with the bone healing and bone metabolism.
13. Chronic, ongoing, or planned use of medications that might affect bone metabolism or bone quality such as bisphosphonates, steroids, methotrexate, anticoagulant therapies, immunosuppressant therapy or immunotherapy.
14. Patient was breastfed less than 1 year before the lipo-aspiration.
15. Any condition which, in the opinion of the investigator, could interfere with trial conduct, the patient’s compliance with the protocol or influence interpretation of the results.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Short term safety focusses on ATC and NVD 003 related (S)AEs between screening and 3 months post-GS (V6 included)
2. Mid long-term safety focusses on the NVD 003 graft implantation, NVD 003 related (S)AEs and the surgical reintervention rate, including all corrective surgeries following a confirmed failure of the index surgery, captured between 3 months (V6 excluded) and 12 months post-GS (V8 included)
3. Long-term safety evaluates the NVD 003 related SAEs between 12 months post-GS (V8 excluded) and 24 months (V9 included)

Secondary endpoints 5

1. Based on CT-scan • Centrally analyze the tibial length difference at GS and 12 months post-GS • Centrally analyze the bone formation at 3-, 6-, and 12-months post GS • Centrally analyze bone union and remodeling at 12 months post-GS
2. Based on X-ray: • Centrally analyze the positioning of the graft at 6 weeks and 24 months post-GS • Centrally analyze the alignment of the concerned bones and fixation devices at 6 weeks and 24 months post-GS • Centrally evaluate bone growth based on tibial length evolution and leg length differences between both legs at 6 weeks and 24 months post-GS
3. Assess the clinical evolution of the patient, before and after the grafting surgery, by means of the investigator assessed “Clinical Global Impression”, Severity Scale (CGI-S) and Improvement Scale (CGI-I) at screening, at hospital discharge, 6 weeks, 3-, 6-, 12-, and 24-months post-grafting. a. CGI-S b. CGI-I:
4. a. CGI-S i. Screening: general functioning, walking ability, weight bearing, presence of pain and pain at palpation, appearance of the leg, social activities (including school attendance and sports activities).
5. b. CGI-I: i. Hospital discharge and 6 weeks post-GS: general functioning, presence of pain and pain at palpation, appearance of the leg ii. 3 months-24 months post-GS: general functioning, walking ability, weight bearing, presence of pain and pain at palpation, appearance of the leg, social activities (including school attendance and sports activities).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novadip Biosciences

Sponsor organisation

Novadip Biosciences

Address

Rue Granbonpre 11

City

Mont-Saint-Guibert

Postcode

1435

Country

Belgium

Scientific contact point

Organisation

Novadip Biosciences

Contact name

Denis Dufrane

Public contact point

Organisation

Novadip Biosciences

Contact name

Denis Dufrane

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

3 submissions — initial application plus substantial / non-substantial modifications