Cryopreserved Human Umbilical Cord as a Meningeal Patch in Fetoscopic Spina Bifida Repair

Study Overview
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Brief Summary
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The objective is to test the efficacy of a laparotomy-assisted fetoscopic surgical approach to cover spina bifida spinal cord developmental defects using cryopreserved human umbilical cords (NEOX Cord 1K®) as a meningeal and skin patch.

Official Title
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Cryopreserved Human Umbilical Cord as a Meningeal Patch in Fetoscopic Spina Bifida Repair: Single Arm Phase III Trial.

Conditions
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Spina Bifida; Fetus, 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 ≤45 kg/m2 (pre-pregnancy) No preterm birth risk factors (short cervix <20 mm or a 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 a normal chromosomal microarray analysis (CMA), or a CMA with variants of unknown significance [fluorescence in situ hybridization (FISH) acceptable if ≥ 24 weeks]. Exclusion Criteria: Maternal Exclusion Criteria: Non-resident of the United States Multifetal pregnancy Poorly controlled insulin-dependent pregestational diabetes Poorly controlled A2 diabetes mellitus (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 > 45 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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Female

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 Pediatric 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® (human umbilical cord) will be used for skin closure at the discretion of the Pediatric 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 participants that can ambulate independently by walking at least 10 steps |  | 30-36 months after delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with lower extremity motor and sensory levels exceeding the anatomical level of the lesion by ≥ 2 segments |  | 30-36 months after delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fetoscopic fetal intervention, Human umbilical cord, NEOX Cord 1K