ClinicalTrials.gov record NCT04532047

PEARL (PrEnAtal Enzyme Replacement Therapy for Lysosomal Storage Disorders)

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Jul 27, 2026

PEARL (PrEnAtal Enzyme Replacement Therapy for Lysosomal Storage Disorders)

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 1An early-stage study, usually small, mainly to check safety, side effects and how much of a treatment can be given. Whether it works is not the main question yet.
Age18 years old to 50 years old
SexAll
LocationUnited States
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This Phase 1 study tests the safety and feasibility of giving enzyme replacement therapy directly to fetuses diagnosed in utero with certain lysosomal storage disorders. The enzyme is typically infused into the fetal umbilical vein and repeated every 2–4 weeks during pregnancy. The study will monitor maternal and fetal safety, whether full doses can be delivered, laboratory markers, and clinical outcomes over time.

What it is studying. The study is trying to determine whether administering enzyme replacement (Aldurazyme/laronidase) directly to the fetus during pregnancy is feasible and what maternal and fetal safety issues occur. Outcomes being tracked include treatment-related adverse events, whether full weight-based fetal doses can be given, levels of disease-related substances in urine (glycosaminoglycans), improvement or resolution of fetal hydrops if present, and whether antibodies to the enzyme develop.

What the researchers hope to learn. To learn whether in utero enzyme replacement can be delivered safely and reliably; to measure treatment-related adverse events, dosing feasibility, changes in urine glycosaminoglycans, improvement of hydrops, and development of antibodies to the enzyme.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

For detailed information, please view our study website: https://pearltrial.ucsf.edu/ The investigators aims to determine the the maternal and fetal safety and feasibility of in utero fetal enzyme replacement therapy in fetuses with Lysosomal Storage Diseases.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Aldurazyme (laronidase)

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

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:
  • inability to complete the procedure secondary to maternal body habitus or placental location
  • significant cardiopulmonary disease
  • mirror syndrome
  • end organ failure
  • altered mental status
  • placental abruption
  • active preterm labor
  • preterm premature rupture of membranes.
  • Mother will require therapeutic dosing of anticoagulation within 24 hours prior to or following the intervention.

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Detailed description from the registry

Because fetuses with these LSDs are at increased risk of serious perinatal morbidity and mortality, particularly in the setting of Non-Immune Hydrops Fetalis (NIHF), the administration of the approved enzyme therapy in utero has the potential to significantly improve outcomes for affected fetuses. The perinatal death rate associated with NIHF ranges from 30 to 75%, so development of an in utero approach to treatment could be of significant benefit. The in utero period has been shown to be a time of relative fetal tolerance to immune stimuli, and this tolerance may lead to improved response to ERT in situations where postnatal initiation instead leads to antibody development and impaired response to treatment. It is also probable that in some cases, initiation of ERT in utero leads to improved neurodevelopmental outcomes if the replaced enzyme impacts the neurologic system during critical periods of development. This is a phase 1 clinical trial to determine the safety and feasibility of fetal enzyme replacement therapy in fetuses with LSD

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participation involves an invasive fetal procedure in which enzyme replacement is delivered into the fetal umbilical vein (typically near the cord insertion). Doses are weight‑based (adjusted for estimated fetal weight) and treatments are planned to be repeated every 2–4 weeks during pregnancy. Monitoring will include prenatal ultrasounds and echocardiograms (for hydrops), blood and urine testing (including antibody levels and urine GAGs), and ongoing safety follow‑up; outcomes are tracked for several years (registry timeframes up to six years). The pregnant woman must provide written informed consent and attend study visits and monitoring.

How the study is structured. Phase 1 interventional (treatment) trial with a single group: all enrolled pregnancies receive in utero enzyme replacement. Procedures involve infusion into the fetal umbilical vein, near where the cord inserts into the placenta, with dosing adjusted by estimated fetal weight and repeated every 2–4 weeks. There is no masking (open-label). Participants and infants are followed for outcomes and safety measures reported up to several years.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
  • The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on Pompe disease

This trial is also listed on this site under Gaucher disease, Hunter syndrome and Hurler syndrome.

Clinical trials32 trials listed for Pompe diseaseEvery trial the registry lists for Pompe disease, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in Pompe disease researchLatest monthly update: September 2026. Includes: Antibody effects. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Jul 1, 2021
Primary completion
Jul 31, 2031 (estimated)
Study completion
Jul 31, 2032 (estimated)
Target enrollment
10 participants (estimated)
Last updated on registry
Mar 17, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
University of California, San Francisco
Principal investigator
Tippi Mackenzie, Professor of Surgery
University of California, San Francisco
Collaborators
  • Duke University

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

Terms used on this page · explanations by MedicalUpdates.ai

written informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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