This is the classic website, which will be retired eventually. Please visit the modernized instead.
Working… Menu

In Utero Enzyme Replacement Therapy for Lysosomal Storage Diseases (IUERT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04532047
Recruitment Status : Recruiting
First Posted : August 31, 2020
Last Update Posted : September 21, 2023
Duke University
Information provided by (Responsible Party):
Tippi Mackenzie, University of California, San Francisco

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
MPS I MPS II MPS IVA MPS VI Mps VII Gaucher Disease, Type 2 Gaucher Disease, Type 3 Pompe Disease Infantile-Onset Wolman Disease Drug: Aldurazyme (laronidase) Phase 1

Detailed Description:

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: In Utero Enzyme Replacement Therapy (ERT) for Prenatally Diagnosed Lysosomal Storage Disorders (LSDs).
Actual Study Start Date : July 1, 2021
Estimated Primary Completion Date : July 2031
Estimated Study Completion Date : July 2032

Arm Intervention/treatment
Experimental: Experimental: in utero enzyme replacement therapy
ERT will be delivered in utero. Typically, the target of the procedure to administer in utero ERT will be the umbilical vein near the insertion of the umbilical cord into the placenta. The dose of the ERT will be dependent on the specific disease process and enzyme being replaced, and the estimated weight of the fetus. The dosage will be the same as the recommended weight-based postnatal dosing, adjusted for estimated fetal weight. IUERT will be repeated every 2-4 weeks, which is an interval consistent with the standard of care for IUTs (every 2-4 weeks) to avoid excessive access through the umbilical vein. This interval is also consistent with the half-life of each relevant enzyme.
Drug: Aldurazyme (laronidase)
Enzyme replacement therapy for lysosomal storage diseases
Other Names:
  • Elaprase (idursulfase)
  • Vimizim (elosulfase alfa)
  • Naglazyme (galsulfase)
  • Mepsevii (vestronidase alfa-vjbk)
  • Lumizyme (alglucosidase alfa)
  • Kanuma (sebelipase alfa)

Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. [ Time Frame: 6 years ]
    Adverse and serious adverse events including, but not limited to, death within 24 hours after the procedure, stillbirth, death prior to initial hospital discharge,increased response with antibody development above that expected with postnatal ERT, and serious related or serious unexpected adverse events exceeding those expected with the natural history of treated disease during the first five years of life, assessed by CTCAE v5.0.

  2. Number of participants to receive the full initial, weight-based dose of enzyme replacement therapy through the fetal umbilical vein, and subsequent doses throughout the pregnancy. [ Time Frame: 6 years ]
    full dose administration compared to the need to halt the intervention prior to administration of a full dose.

  3. Number of participants with the presence and levels of glycosaminoglycans (GAGs) in urine. [ Time Frame: 6 years ]
    Laboratory analysis of urine for GAG levels.

  4. The number of participants with improvement or resolution of hydrops (if present). [ Time Frame: 6 years ]
    Improvement of hydrops via ultrasound and echocardiogram results (if present).

Secondary Outcome Measures :
  1. Number of participants that show measured levels of antibodies against the enzyme. [ Time Frame: 6 years ]
    Laboratory analysis of blood to measure antibody levels.

Other Outcome Measures:
  1. Number of participants that show functional cardiac, growth, mobility, and neurocognitive function. [ Time Frame: 6 years ]
    ecogardiogram, skeletal survey, neurocognitve assessments such as Bayley III to assess cardiac, growth, mobility and neurocognitive function.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Maternal pregnant women of age 18-50, carrying a male or female fetus at 18 0/7 weeks to 34 6/7 weeks.
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04532047

Layout table for location contacts
Contact: Tippi MacKenzie, MD 415-476-4086
Contact: Emma Canepa, MS, CCRP 415-476-7255

Layout table for location information
United States, California
University of California Recruiting
San Francisco, California, United States, 94158
Contact: Emma Canepa, MS, CCRP    415-476-7255   
Sponsors and Collaborators
University of California, San Francisco
Duke University
Layout table for investigator information
Principal Investigator: Tippi MacKenzie, MD University of California, San Francisco
Publications of Results:

Layout table for additonal information
Responsible Party: Tippi Mackenzie, Professor of Surgery, University of California, San Francisco Identifier: NCT04532047    
Other Study ID Numbers: 20-31520
First Posted: August 31, 2020    Key Record Dates
Last Update Posted: September 21, 2023
Last Verified: September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Gaucher Disease
Glycogen Storage Disease Type II
Wolman Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Glycogen Storage Disease
Carbohydrate Metabolism, Inborn Errors
Cholesterol Ester Storage Disease
Infant, Newborn, Diseases