Fetoscopic NEOX Cord 1K® Spina Bifida Repair

Study Overview
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Brief Summary
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To fetoscopically use cryopreserved human umbilical cord allografts, named NEOX Cord 1K®, as a spinal cord cover of spina bifida defects. This procedure will be performed to create a watertight seal covering over the spinal cord in order to decrease the incidence rates of postnatal morbidities. For larger skin defects, NEOX Cord 1K® may be used as a skin cover.

Official Title
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Fetoscopic Spina Bifida Repair Using a Cryopreserved Human Umbilical Cord Allograft (NEOX Cord 1K®) as a Meningeal Patch

Conditions
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Spina Bifida, Myelomeningocele, Myeloschisis

Intervention / Treatment
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* Device: NEOX Cord 1K applied fetoscopically


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Maternal inclusion criteria: Singleton pregnancy Gestational age at screening is 19 to 25 5/7 weeks and gestational age at surgery is 22 to 25 6/7 weeks Maternal age: 18 years and older Body mass index < 40 kg/m2 No preterm birth risk factors (short cervix, history of previous preterm delivery) No previous uterine incision in the active uterine segment Willing to undergo an open fetal repair if the fetoscopic approach is unsuccessful Fetal inclusion criteria: Spina bifida defect between T1 to S1 vertebral levels Chiari II malformation No evidence of kyphosis (curved spine) No major life-threatening fetal anomaly unrelated to spina bifida Normal karyotype, or normal CMA, or a CMA with variants of unknown significance Exclusion Criteria: Maternal exclusion criteria: Non-resident of the United States Multifetal pregnancy Poorly controlled insulin-dependent pregestational diabetes Poorly controlled A2DM insulin-dependent diabetes Current or planned cerclage or documented history of an incompetent cervix Placenta previa or placental abruption Short cervix of < 20 mm Obesity as defined by a body mass index of > 40 kg/m2 Previous spontaneous singleton delivery prior to 37 weeks Maternal-fetal Rh isoimmunization, Kell sensitization, or a history of neonatal alloimmune thrombocytopenia HIV or Hepatitis-B positive status Known Hepatitis-C positivity Uterine anomaly such as large or multiple fibroids or a mullerian duct abnormality that is diagnosed via imaging prior to surgery, which that are unavoidable during surgery Other medical conditions which are contraindication to surgery or general anesthesia Patient does not have a support person Inability to comply with the travel and follow-up requirements of the trial Patient does not meet psychosocial standardized assessment criteria Participation in this or another intervention study that influences maternal and fetal morbidity and mortality Maternal hypertension Zika virus positivity Allergy/history of drug reaction to Amphotericin B Fetal exclusion criteria: Major fetal anomaly not related to spina bifida Kyphosis in the fetus of 30 degrees or more Ventriculomegaly greater than 15 mm and no movements noted at hip and knee joints

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NEOX Cord 1K applied fetoscopically<br>Patients intending to undergo open in-utero spina bifida repair, will be offered to be screened for an alternative minimally invasive approach. All eligible pregnant mothers' fetuses within the trial will receive NEOX Cord 1K® as a spinal cord cover to close the developmental defect. In some cases, at the discretion of the Neurosurgeon, NEOX Cord 1K® may be required to cover the skin. All eligible subjects meeting all inclusion criteria but none of the exclusion criteria may be enrolled. | Device: NEOX Cord 1K applied fetoscopically<br>* Under general anesthesia and tocolysis, in-utero repair begins with a laparotomy that is followed by exteriorization of the uterus. The fetus is then positioned by external cephalic version. Uterine entry will be accessed using 3 cannulas, followed by heated-humidified carbon dioxide insufflation for visualization. Then, fetoscopically the placode will be examined and dissected. The lesion will be repaired using NEOX Cord 1K® (HUC) for closure of the first layer over the neural placode. Primary closure of the skin will then occur, or NEOX Cord 1K® (HUC) will be used for skin closure at the discretion of the neurosurgeon. Finally, the laparotomy site will be sutured in multiple layers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with successful fetoscopic repair of the defect using NEOX Cord 1K® | A digital image of the fetal repair site will be captured during and immediately after the repair. The images will be sent to three independent blinded neurosurgeons for review of successful closure of the defect. More than best of three votes will be considered as the result. | Immediately after repair procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with intact repair of the defect, defined as no cerebrospinal fluid leakage and no dehiscence at the repair site. |  | Birth | 
| Number of patients with intact repair of the defect as defined as no cerebrospinal fluid leakage and no dehiscence at the repair site. |  | 12 months ± 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neox Cord 1K, Fetoscopic repair, Cryopreserved human umbilical cord