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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 4
- 主要终点
- To assess the efficacy of NVD003 for the surgical treatment of CPT in pediatric participants
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of NVD003 in pediatric participants with unilateral Congenital Pseudarthrosis of the Tibia (CPT) compared with iliac crest bone graft (ICBG) at 12 months post graft surgery.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Participant is of any sex, ≤17 years of age.
- •Participant has been diagnosed with CPT (with or without NF1).
- •Participant has a non-healing Paley type 3 or 4 diaphyseal fracture.4
- •Participant is a candidate for surgical treatment using an internal fixation approach (intramedullary rod) based on CPT fracture status and general health status.
- •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.
- •Participant can provide an adequate ATC sample volume.
- •Participant weighs ≥5 kg/11 lb at Screening and on Day
- •Participant is not pregnant or lactating.
- •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:
- •Intravaginal
- •Transdermal
- •Progestogen-only hormonal contraception associated with inhibition of ovulation:
- •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.
- •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.
排除标准
- •Participant has bilateral CPT.
- •Participant has evidence of plexiform neurofibroma of any size or nodular fibroma ≥1.2 inches/3 cm on the ipsilateral leg.
- •Participant has a clinically significant infection at the fracture site or systemic infection.
- •Participant's CPT fracture involves the metaphysis (i.e., not limited to the diaphysis).
- •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.
- •Participant has an autoimmune disease, with the exception of well-controlled type 1 diabetes or autoimmune thyroid disorders.
- •Participant has an active (malignant) tumor.
- •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.
- •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.
- •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.
- •Participant has received any investigational product (including a device) within 60 days before enrollment in the study.
- •Participant would be concurrently enrolled in another clinical study while participating in this study.
- •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.).
- •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.
研究组 & 干预措施
Experimental Arm
surgical grafting procedure: internal fixation with cross-union using NVD003
干预措施: NVD003 (Biological)
Standard of Care Arm
Either a single-stage grafting surgery with internal fixation and cross-union or the 2-stage "induced membrane" grafting surgery approach, depending on the surgeon's own standard of Care.
干预措施: Iliac Crest Bone Graft (Procedure)
结局指标
主要结局
To assess the efficacy of NVD003 for the surgical treatment of CPT in pediatric participants
时间窗: At 12 months post GS
Overall healing at 12 months, defined as a binary (yes/no) outcome derived from the following 3 outcomes: * Radiographic healing, defined as a score ≥13 on the modified Radiological Union Scale for Tibia (mRUST) scale (range 1 to 16) assessed by independent central readers (ICRs) * Clinical healing measured by the absence of pain with weight-bearing, based on clinician's assessment * No use of secondary interventions to promote or accelerate bone healing All 3 criteria must be met for a "yes" on overall healing for this endpoint to be achieved.
次要结局
- Efficacy: To assess the efficacy of NVD003 with respect to individual components of overall healing - radiographic healing(12 months after grafting surgery)
- Efficacy: To assess the efficacy of NVD003 with respect to individual components of overall healing - clinical healing(12 months after grafting surgery)
- Efficacy: To assess the efficacy of NVD003 with respect to individual components of overall healing - No use of secondary intervention(12 months after grafting surgery)
- Safety: To assess the safety of NVD003 for the surgical treatment of CPT in pediatric participants - Adverse events(12 months after grafting surgery)
- Safety: To assess the safety of NVD003 for the surgical treatment of CPT in pediatric participants - Serious adverse events(12 months after grafting surgery)
- Safety: To assess the safety of NVD003 for the surgical treatment of CPT in pediatric participants - Units of blood transfused perioperatively(from start of surgical procedure (Day 1) until hospital discharge)
- Safety: To assess the safety of NVD003 for the surgical treatment of CPT in pediatric participants - Duration of Grafting Surgery(Grafting Surgery (Day 1))
- Safety: To assess the safety of NVD003 for the surgical treatment of CPT in pediatric participants - duration of hospitalization(from grafting surgery (Day 1) until hospital discharge)
- Safety: To assess the safety of NVD003 for the surgical treatment of CPT in pediatric participants - Recurrent fracture(12 months after grafting surgery)
- To further evaluate the efficacy of NVD003 for the surgical treatment of CPT in pediatric participants based on other measures of bone healing - Radiological(Post grafting surgery (Day 1), and at months 3, 6 and 12)
- To further evaluate the efficacy of NVD003 for the surgical treatment of CPT in pediatric participants based on other measures of bone healing - functional walking(Post grafting surgery (Day 1), and at months 3, 6 and 12)
- To evaluate the effects of NVD003 on quality of life (QoL)(Baseline and months 6 and 12 post grafting surgery)