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

Overview

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.

Full Title of Study: “Cryopreserved Human Umbilical Cord as a Meningeal Patch in Fetoscopic Spina Bifida Repair: Single Arm Phase III Trial.”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)
• Study Primary Completion Date: March 8, 2031

Interventions

• Device: NEOX Cord 1K applied fetoscopically
  • 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.

Arms, Groups and Cohorts

• Experimental: NEOX Cord 1K applied fetoscopically
  • 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.

Clinical Trial Outcome Measures

Primary Measures

• Number of participants that can ambulate independently by walking at least 10 steps
  • Time Frame: 30-36 months after delivery

Secondary Measures

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

Participating in This Clinical Trial

Inclusion Criteria

Maternal Inclusion Criteria:

1. Singleton pregnancy 2. Gestational age at screening is 19 to 25 5/7 weeks and gestational age at surgery is 22 to 25 6/7 weeks 3. Maternal age: 18 years and older 4. Body mass index ≤45 kg/m2 (pre-pregnancy) 5. No preterm birth risk factors (short cervix <20 mm or a history of previous preterm delivery) 6. No previous uterine incision in the active uterine segment 7. Willing to undergo an open fetal repair if the fetoscopic approach is unsuccessful Fetal Inclusion Criteria:

1. Spina bifida defect between T1 to S1 vertebral levels 2. Chiari II malformation 3. No evidence of kyphosis (curved spine) 4. No major life-threatening fetal anomaly unrelated to spina bifida 5. 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:

1. Non-resident of the United States 2. Multifetal pregnancy 3. Poorly controlled insulin-dependent pregestational diabetes 4. Poorly controlled A2 diabetes mellitus (A2DM) insulin-dependent diabetes 5. Current or planned cerclage or documented history of an incompetent cervix 6. Placenta previa or placental abruption 7. Short cervix of < 20 mm 8. Obesity as defined by a body mass index of > 45 kg/m2 9. Previous spontaneous singleton delivery prior to 37 weeks 10. Maternal-fetal Rh isoimmunization, Kell sensitization, or a history of neonatal alloimmune thrombocytopenia 11. HIV or Hepatitis-B positive status 12. Known Hepatitis-C positivity 13. 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 14. Other medical conditions which are contraindication to surgery or general anesthesia 15. Patient does not have a support person 16. Inability to comply with the travel and follow-up requirements of the trial 17. Patient does not meet psychosocial standardized assessment criteria 18. Participation in this or another intervention study that influences maternal and fetal morbidity and mortality 19. Maternal hypertension 20. Zika virus positivity 21. Allergy/history of drug reaction to Amphotericin B Fetal exclusion criteria:

1. Major fetal anomaly not related to spina bifida 2. Kyphosis in the fetus of 30 degrees or more 3. Ventriculomegaly greater than 15 mm and no movements noted at hip and knee joints

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • The University of Texas Health Science Center, Houston
• Provider of Information About this Clinical Study
  • Principal Investigator: Ramesha Papanna, Professor – The University of Texas Health Science Center, Houston
• Overall Official(s)
  • Ramesha Papanna, MD, MPH, Principal Investigator, The University of Texas Health Science Center, Houston
• Overall Contact(s)
  • Ramesha Papanna, MD, MPH, (713) 500-6423, Ramesha.Papanna@uth.tmc.edu