Detailed Description
CPT is a rare disorder affecting the tibia and/or the ipsilateral fibula in children. The disease is usually diagnosed during the first year of life and is characterized by nonunion of a tibial diaphyseal fracture that either develops spontaneously or after a history of trivial trauma in a previously dysplastic segment of the bone. The treatment of CPT remains a challenge, often due to failure of ICBG to achieve and maintain bone union, resulting in multiple revision surgeries and occasionally amputation of the lower leg. NVD003 is a novel 3-dimensional osteogenic graft that is derived from autologous adipose stem cells combined with hydroxyapatite/beta-tricalcium phosphate particles. As an alternative to ICBG, NVD003 is intended to promote bone formation and support the bone healing process, even in severely disturbed pathophysiological conditions like CPT.
This is a prospective, randomized, controlled, multicenter, phase 3 clinical study in pediatric participants with CPT who have a non-healing Paley type 3 or 4 diaphyseal fracture and are candidates to undergo surgical treatment with internal fixation (intramedullary rod).
Eligibility Criteria
Age Range: No minimum to 17 years
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.