In utero enzyme replacement therapy for lysosomal storage disorders
PEARL (PrEnAtal Enzyme Replacement Therapy for Lysosomal Storage Disorders)
PHASE1 · University of California, San Francisco · NCT04532047
This study is testing whether giving enzyme replacement therapy to unborn babies with lysosomal storage disorders can improve their health and development before they are born.
Quick facts
| Phase | PHASE1 |
|---|---|
| Study type | Interventional |
| Enrollment | 10 (estimated) |
| Ages | 18 Years to 50 Years |
| Sex | Female |
| Sponsor | University of California, San Francisco (other) |
| Locations | 1 site (San Francisco, California) |
| Trial ID | NCT04532047 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to evaluate the safety and feasibility of administering enzyme replacement therapy to fetuses diagnosed with lysosomal storage disorders (LSDs) during pregnancy. The study focuses on fetuses at risk of serious complications, particularly those with Non-Immune Hydrops Fetalis (NIHF), which has a high perinatal mortality rate. By delivering the enzyme therapy in utero, the researchers hope to improve outcomes and potentially enhance neurodevelopmental results by addressing the condition during critical developmental periods. This phase 1 trial will assess the initial safety of the treatment approach.
Who should consider this trial
Good fit: Ideal candidates include pregnant women aged 18 to 50 carrying live fetuses diagnosed with specific lysosomal storage disorders between 18 to 34 weeks of gestation.
Not a fit: Patients with fetuses that have severe structural anomalies or additional unrelated pathogenic genetic variants may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly reduce perinatal morbidity and mortality for fetuses affected by lysosomal storage disorders.
How similar studies have performed: While the concept of in utero treatment is promising, this specific approach to enzyme replacement therapy for lysosomal storage disorders is novel and has not been extensively tested in previous studies.
Eligibility criteria
Show full inclusion / exclusion 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.
Where this trial is running
San Francisco, California
- University of California — San Francisco, California, United States (RECRUITING)
Study contacts
- Principal investigator: Tippi MacKenzie, MD — University of California, San Francisco
- Study coordinator: Tippi MacKenzie, MD
- Email: tippi.mackenzie@ucsf.edu
- Phone: 415-476-4086
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: MPS I, MPS II, MPS IVA, MPS VI, Mps VII, Gaucher Disease, Type 2, Gaucher Disease, Type 3, Pompe Disease Infantile-Onset