Cellular Therapy for In Utero Repair of Myelomeningocele - The CuRe Trial

NCT04652908 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 1617774
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Spina bifida, or myelomeningocele (MMC), is a birth defect that results in paralysis, excess fluid on the brain (hydrocephalus), and impaired ability to urinate and have bowel movements normally. In a previous study (the MOMS trial), surgery before birth (in-utero/fetal surgery) was shown to reduce the need for shunting for hydrocephalus. There was also some improvement in ambulation, but 58 % of the children still could not walk unassisted. This study is testing living stem cells from placenta added to the fetal repair in an effort to improve the ability to walk. Previous animal studies have shown dramatic improvement in walking and bowel and bladder function when placental stem cells are added to MMC repair. Use of these "living" cells may protect the developing spinal cord, prevent further injury, and may even reverse existing damage to the nerves that control movement. This study is assessing the safety and efficacy of adding stem cells to open fetal surgery for MMC in humans.

Conditions

Myelomeningocele

Outcome Measures

Primary Outcomes (1)

• Safety of the placenta-derived mesenchymal stem cell (PMSC-ECM) Product

  Will be assessed by evaluating the presence or absence of cerebrospinal fluid leak, infection at the MMC repair site, failure of the MMC repair site to heal, and any unexpected growths or tumor formation. These will be assessed at birth by physical exam, brain and spinal ultrasound , and brain and spinal MRI.

  Assessed at birth

Secondary Outcomes (1)

• Efficacy of the PMSC-ECM Product

  30 months.

Study Arms (2)

Treatment with PMSC-ECM

EXPERIMENTAL

One-time administration of PMSC-ECM during the course of in utero fetal myelomeningocele surgery will be administered

Biological: Placental Mesenchymal Stem Cells seeded on a commercially available dural graft extracellular matrix

non-PMSC untreated contemporaneous cohort

OTHER

Contemporaneous cohort of patients undergoing routine fetal or postnatal MMC repair without PMSC-ECM (non-PMSC untreated contemporaneous cohort).

Other: Untreated contemporaneous cohort

Interventions

Placental Mesenchymal Stem Cells seeded on a commercially available dural graft extracellular matrix BIOLOGICAL

As in the current standard fetal surgery, under sonographic guidance, initial uterine entry will be accomplished by uterine stapling device or similar. The fetus will be given an intramuscular injection of pain medications and paralytic. The myelomeningocele will be closed in a standardized manner under magnification. As in the standard fetal operation, the spinal cord will be dissected from surrounding tissue and allowed to drop into the spinal canal. The PMSC-ECM product will then be tailored to the size of the spinal cord and applied topically, cell side down. The PMSC-ECM product will be sutured in place to the dura. Finally, the fetal skin will be closed in the standard fashion. The amniotic fluid volume will be replaced and antibiotics will be added. The uterus will be closed. The abdominal fascial layer and skin will be closed in routine fashion.

Also known as: PMSC-ECM

Treatment with PMSC-ECM

Untreated contemporaneous cohort OTHER

The addition of a non-PMSC treated cohort, the untreated contemporaneous cohort, has been added at the request of the FDA to provide contemporaneous patients for validation of the continued relevance of use of the outcomes of the MOMS trial as the comparison arm for the Phase 2a portion of the study.

Also known as: non-PMSC-ECM

non-PMSC untreated contemporaneous cohort

Eligibility Criteria

• Age: 19 Weeks - 25 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Eligibility for fetal surgery per the MOMS trial, which are:
• Myelomeningocele (including myeloschisis) at any level from T1 through S1 with hindbrain herniation. Lesion level will be confirmed by ultrasound and hindbrain herniation will be confirmed by MRI at the UC Davis Fetal Center
• Maternal age ≥18 years
• Gestational age at enrollment between 19 weeks 0 days and 25 weeks 6 days gestation as determined by clinical information and evaluation of first ultrasound
• Normal karyotype. Results by fluorescence in situ hybridization (FISH) will be acceptable if the patient is greater than 24 weeks gestation;

You may not qualify if:

• Not being eligible for fetal surgery per the MOMS trial, which includes:
• Multifetal pregnancy
• Insulin dependent pregestational diabetes
• Fetal anomaly not related to myelomeningocele.
• Kyphosis in the fetus of 30 degrees or more
• Current or planned cerclage or documented history of incompetent cervix, placenta previa or placental abruption
• Short cervix \< 20 mm measured by cervical ultrasound
• Obesity as defined by body mass index of 35 or greater
• Previous spontaneous singleton delivery prior to 37 weeks
• Maternal-fetal Rh isoimmunization, Kell sensitization or a history of neonatal alloimmune thrombocytopenia
• Maternal HIV or Hepatitis-B status positive due to the increased risk of transmission to the fetus during maternal-fetal surgery. If the patient's HIV or Hepatitis B status is unknown, the patient must be tested and found to have negative results before she can be enrolled
• Known Hepatitis-C positivity. If the patient's Hepatitis C status is unknown, she does not need to be screened
• Uterine anomaly such as large or multiple fibroids or Müllerian duct abnormality
• Other maternal medical condition which is a contraindication to surgery or general anesthesia. This includes any patient with a previous hysterotomy in the active segment of the uterus (whether from a previous classical cesarean, uterine anomaly such as an arcuate or bicornuate uterus, major myomectomy resection, or previous fetal surgery)
• Patient does not have a support person (e.g., husband, partner, mother)

Sponsors & Collaborators

• University of California, Davis: lead
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (1)

UC Davis Health

Sacramento, California, 95817, United States

RECRUITING

Related Publications (1)

• Farmer DL, Kumar P, Reynolds E, Lee SY, Powne AB, Pivetti CD, Zwienenberg M, McLennan AS, Nolta JA, Brown EG, Saadai P, Hirose S, Wang A. Feasibility and safety of cellular therapy for in-utero repair of myelomeningocele (CuRe Trial): a first-in-human, phase 1, single-arm study. Lancet. 2026 Feb 28;407(10531):867-875. doi: 10.1016/S0140-6736(25)02466-3.

  PMID: 41763744 DERIVED

MeSH Terms

Conditions

Meningomyelocele

Condition Hierarchy (Ancestors)

Neural Tube Defects; Nervous System Malformations; Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Diana L Farmer, MD

  UC Davis School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy B Powne, MSN, RN

CONTACT

916-794-2229; fctc@health.ucdavis.edu

Maria G Hernandez

CONTACT

916-734-4156; mghernandez@health.ucdavis.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Treatment arm subjects receiving PMSC-ECM (Placental Mesenchymal Stem Cells seeded on a commercially available dural graft extracellular matrix). Additionally, we will follow a contemporaneous cohort of patients undergoing routine fetal or postnatal MMC repair without PMSC-ECM (non-PMSC untreated contemporaneous cohort). 35 participants will be enrolled under the treatment arm and 20 participants will be enrolled under the untreated contemporaneous cohort. The addition of a non-PMSC treated cohort, the untreated contemporaneous cohort, has been added at the request of the FDA to provide contemporaneous patients for validation of the continued relevance of use of the outcomes of the MOMS trial as the comparison arm for the Phase 2a portion of the study.

Study Record Dates

• First Submitted: November 25, 2020
• First Posted: December 3, 2020
• Study Start: June 21, 2021
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)