PEARL (PrEnAtal Enzyme Replacement Therapy for Lysosomal Storage Disorders)

Launched by UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · Aug 25, 2020

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called in utero enzyme replacement therapy for pregnant women carrying fetuses diagnosed with certain genetic disorders known as lysosomal storage diseases (LSDs). These diseases, which include conditions like MPS I, Gaucher Disease, and Pompe Disease, can lead to serious health issues for the baby. The goal of the trial is to find out if this therapy is safe for both the mother and the baby when given before birth.

To be eligible for this trial, women must be between 18 and 50 years old and be carrying a live male or female fetus between 18 to 34 weeks of pregnancy. The fetus must have been diagnosed with one of the listed LSDs through specific tests. Participants will undergo procedures to deliver the enzyme therapy to the fetus, and they will be monitored closely throughout the study. It’s important to note that certain conditions in the mother or fetus may exclude them from participation, but the study is open to many women who meet the criteria and can provide informed consent.

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• • Live male or female fetuses at 18 0/7 weeks to 34 6/7 weeks gestation
• • Diagnosis of one of the 8 included LSDs in utero by genetic or enzymatic analyses performed on amniotic fluid, fetal blood, placental tissue, or other samples through chorionic villus sampling (CVS), amniocentesis, cordocentesis, cell free fetal DNA, or other procedures. In the event that parents are identified as genetic carriers for a LSD, diagnostic testing for the fetus would be performed to confirm the diagnosis
• • Pregnant women age 18 years to 50 years, carrying a live male or female fetus at 18 0/7 weeks to 34 6/7 weeks gestation
• • Identified through the above listed means to be carrying a fetus with an LSD.
• • Ability to give written informed consent and comply with the requirements of the study.
• Exclusion Criteria:
• • Fetuses with a concurrent severe structural anomaly
• • Fetuses with an additional pathogenic genetic variant not related to the underlying LSD that contribute a significant risk of morbidity or mortality.
• • Hydrops fetalis will not be an exclusion criterion because ERT has the possibility of significant benefit in this situation.
• * Women with one or more significant comorbidities that would preclude fetal intervention including, but not limited to:
• • 1. inability to complete the procedure secondary to maternal body habitus or placental location
• • 2. significant cardiopulmonary disease
• • 3. mirror syndrome
• • 4. end organ failure
• • 5. altered mental status
• • 6. placental abruption
• • 7. active preterm labor
• • 8. preterm premature rupture of membranes.
• • Mother will require therapeutic dosing of anticoagulation within 24 hours prior to or following the intervention.