In Utero Enzyme Replacement Therapy for Lysosomal Storage Diseases (IUERT)
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|ClinicalTrials.gov Identifier: NCT04532047
Recruitment Status : Recruiting
First Posted : August 31, 2020
Last Update Posted : September 21, 2023
|Condition or disease
|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)
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
|Study Type :
|Interventional (Clinical Trial)
|Estimated Enrollment :
|Single Group Assignment
|None (Open Label)
|In Utero Enzyme Replacement Therapy (ERT) for Prenatally Diagnosed Lysosomal Storage Disorders (LSDs).
|Actual Study Start Date :
|July 1, 2021
|Estimated Primary Completion Date :
|Estimated Study Completion Date :
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
- 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.
- 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.
- Number of participants with the presence and levels of glycosaminoglycans (GAGs) in urine. [ Time Frame: 6 years ]Laboratory analysis of urine for GAG levels.
- 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).
- Number of participants that show measured levels of antibodies against the enzyme. [ Time Frame: 6 years ]Laboratory analysis of blood to measure antibody levels.
- 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.
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 ClinicalTrials.gov identifier (NCT number): NCT04532047
|Contact: Tippi MacKenzie, MD
|Contact: Emma Canepa, MS, CCRP
|United States, California
|University of California
|San Francisco, California, United States, 94158
|Contact: Emma Canepa, MS, CCRP 415-476-7255 Emma.Canepa@ucsf.edu
|Tippi MacKenzie, MD
|University of California, San Francisco