NVD003 treatment for congenital pseudarthrosis of the tibia

A Phase 3 Randomized, Controlled Study to Assess the Efficacy and Safety of NVD003 Compared With Iliac Crest Bone Graft in Pediatric Participants Treated Surgically for Congenital Pseudarthrosis of the Tibia

This will try NVD003, an autologous stem-cell–based bone graft, in children with congenital pseudarthrosis of the tibia to see if it leads to better bone healing at 12 months than standard iliac crest bone graft.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: N/A to 17 Years
• Sex: All
• Sponsor: Novadip Biosciences (Industry-sponsored)
• Drugs / interventions: immunotherapy, methotrexate
• Locations: 7 sites (Phoenix, Arizona and 6 other locations)
• Trial ID: NCT07112443 on ClinicalTrials.gov

What this trial studies

This randomized, controlled, multicenter Phase 3 study compares NVD003 — a 3-dimensional osteogenic graft made from a child’s own adipose-derived stem cells combined with hydroxyapatite/β-tricalcium phosphate — to standard iliac crest bone graft in pediatric patients with unilateral Paley type 3 or 4 CPT undergoing intramedullary rod fixation. Participants are randomized at the time of surgery and followed with clinical visits and imaging out to 12 months to determine rates of durable bone union and to monitor safety. The trial includes children up to 17 years who can provide adequate adipose tissue for graft manufacture and meet standard infectious disease screening. Secondary outcomes include safety measures and functional recovery.

Who should consider this trial

Good fit: Children (≤17 years) with unilateral congenital pseudarthrosis of the tibia who have a non-healing Paley type 3 or 4 diaphyseal fracture and are candidates for surgical internal fixation with an intramedullary rod are ideal candidates.

Not a fit: Patients who are not surgical candidates for intramedullary fixation, cannot provide adequate adipose tissue for graft manufacture, weigh under the study minimum, have active infections or contraindicated systemic conditions, or whose fracture has already healed are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, NVD003 could improve durable bone union rates and reduce the need for repeat surgeries or limb amputation in children with CPT.

How similar studies have performed: Small clinical series and early-phase studies of autologous cell-based grafts and synthetic bone scaffolds have shown encouraging signals for bone healing, but randomized phase 3 data specifically in CPT are limited, making this a relatively novel, condition-specific application.

Eligibility criteria

Inclusion Criteria:

1. Participant's parent(s)/legal guardian(s) have provided written informed consent (and assent has been provided by the participant, depending on age) for the study.
2. Participant is of any sex, ≤17 years of age.
3. Participant has been diagnosed with CPT (with or without NF1).
4. Participant has a non-healing Paley type 3 or 4 diaphyseal fracture.4
5. Participant is a candidate for surgical treatment using an internal fixation approach (intramedullary rod) based on CPT fracture status and general health status.
6. Participant has serology and molecular test results at Visits 1 and 2 excluding the presence of human T-cell lymphoma virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and syphilis.
7. Participant can provide an adequate ATC sample volume.
8. Participant weighs ≥5 kg/11 lb at Screening and on Day 1.
9. Participant is not pregnant or lactating.
10. If participant is of childbearing potential, is practicing highly effective methods of birth control from Screening to the end of the study:

    * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

      * Oral
      * Intravaginal
      * Transdermal
    * Progestogen-only hormonal contraception associated with inhibition of ovulation:

      * Oral
      * Injectable
      * Implantable
    * Intrauterine device
    * Intrauterine hormone-releasing system
    * Bilateral tubal occlusion
    * Vasectomized partner
    * Sexual abstinence, defined as refraining from heterosexual intercourse during study participation, is acceptable if this is the participant's usual lifestyle; periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and the lactational amenorrhea method are not acceptable methods of contraception Note: A participant is considered to be of childbearing potential if they are postmenarchal and premenopausal, unless surgically sterile (permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy).

    If participant is sexually active and has a partner who may become pregnant (i.e., neither surgically sterile nor postmenopausal), agrees to use highly effective contraception (e.g., sterilization, birth control pills, Depo Provera injections, or contraceptive implants) from Screening to the end of the study.

    Participant agrees to refrain from donating sperm or eggs from Screening to the end of the study.
11. Participant and parent(s)/legal guardian(s) are able to understand all study information provided and are willing to return to the study facility for all visits, including follow-up evaluations.

Exclusion Criteria:

1. Participant has bilateral CPT.
2. Participant has evidence of plexiform neurofibroma of any size or nodular fibroma ≥1.2 inches/3 cm on the ipsilateral leg.
3. Participant has a clinically significant infection at the fracture site or systemic infection.
4. Participant's CPT fracture involves the metaphysis (i.e., not limited to the diaphysis).
5. Participant has a CPT fracture, for which the surgeon intends to use an external fixation system (e.g., Ilizarov, Taylor spatial frame, rail, etc.) instead of, or in addition to, internal fixation.
6. Participant has an autoimmune disease, with the exception of well-controlled type 1 diabetes or autoimmune thyroid disorders.
7. Participant has an active (malignant) tumor.
8. Participant has documented metabolic bone disease or any disorder, such as, but not limited, to osteogenesis imperfecta and osteomalacia, that could interfere with bone healing and bone metabolism.
9. Participant has any chronic, ongoing, or planned use of medications that might affect bone metabolism or bone quality such as bisphosphonates, steroids, methotrexate, vitamin K antagonists, immunosuppressant therapy, or immunotherapy during the study.

   Note that perioperative treatment with a bisphosphonate is allowed in Cohort A participants randomized to ICBG if its use is deemed SOC by the treating surgeon.
10. Participant has any history of allergic reaction or any anticipated hypersensitivity to any anesthetic agent or any potential hypersensitivity to any of the components of the NVD003 graft (including the CMRL1066 formulation medium) or hypersensitivity related to other factors in the surgical process for the ICBG graft, such as anesthesia, medications, suture materials or fixation devices.
11. Participant has received any investigational product (including a device) within 60 days before enrollment in the study.
12. Participant would be concurrently enrolled in another clinical study while participating in this study.
13. Participant has any clinically significant hematologic, renal, hepatic, and coagulation laboratory abnormalities (i.e., complete blood count, prothrombin time/international normalized ratio, Chem-7, liver function tests, etc.).
14. Participant or participant's parent(s)/legal guardian(s) have an unstable condition (e.g., psychiatric disorder, a recent history of substance abuse) or is otherwise thought to be unreliable or incapable of complying with the requirements of the protocol.

Where this trial is running

Phoenix, Arizona and 6 other locations

• Phoenix Children's Hospital, Inc. — Phoenix, Arizona, United States (Recruiting)
• Loma Linda University Health — Loma Linda, California, United States (Recruiting)
• LifeBridge Health - International Center for Limb Lengthening — Baltimore, Maryland, United States (Recruiting)
• Mayo Clinic — Rochester, Minnesota, United States (Recruiting)
• Cliniques Universitaires Saint-Luc ASBL (CUSCL) — Brussels, Brussels Capital, Belgium (Recruiting)
• CHU Amiens-Picardie — Amiens, Picardie, France (Recruiting)
• Hospital Sant Joan de Déu — Esplugues de Llobregat, Spain (Recruiting)

Study contacts

• Study coordinator: Judy Ashworth, MD

Conditions Congenital Pseudarthrosis of Tibia; tissue engineered therapy; bone graft; autologous; pediatric; congenital; non-union; pseudarthrosis