Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C

• Register: ClinicalTrials.gov
• Last refreshed on: 18 March 2024
• Main ID: NCT03471143
• Date of registration: 07/03/2018
• Prospective Registration: Yes
• Primary sponsor: Washington University School of Medicine
• Public title: Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C
• Scientific title: Phase 1/2a Study of 2-Hydroxypropyl-Beta-Cyclodextrin Therapy for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C
• Date of first enrolment: February 22, 2019
• Target sample size: 12
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03471143
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Patricia I Dickson, MD

• Name: Patricia I Dickson, MD

• Name: Patricia I Dickson, MD
• Affiliation: Washington University School of Medicine

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Age 0 to 6 months of age at time of enrollment, both genders, and any race/ethnicity.

2. Diagnosis of NPC (either NPC1 or NPC2) based upon meeting any of the two following
conditions:

A. Two variants classified as pathogenic or likely pathogenic in NPC1/NPC2 on clinical
laboratory testing, or B. One variant classified as pathogenic or likely pathogenic on
clinical laboratory testing and a positive NPC biochemical marker (oxysterol or bile
acid biomarker or PPCS/Lyso509) test, if acid sphingomyelinase deficiency and
cholesterol ester storage disease have been excluded either by clinical molecular
testing of the SMPD1 and LIPA genes or by clinical biochemical assay for acid
sphingomyelinase and lysosomal acid lipase enzymes (or a combination of enzymatic and
molecular testing).

Variants will be interpreted using the American College of Medical Genetics guidelines
for the interpretation of sequence variants (2015) and testing must be performed by a
CLIA-certified laboratory.

3. Subjects with evidence of NPC-related liver disease as defined by direct bilirubin
(DB) >2mg/dL or DB/total bilirubin ratio >0.2.

4. Ability to travel to a research site.

5. Willing to participate in all aspects of trial design including serial blood
collections.

6. Parent / guardian must provide written informed consent to participate in the study.
Because of the age range intended for inclusion, assent will not possible.

Exclusion Criteria:

1. Age > 6 months at time of enrollment in the trial.

2. A medical condition (such as clinically significant bleeding diathesis or evidence of
immune suppression) that in the opinion of the investigator precludes placement of an
intravenous catheter

3. An absolute neutrophil count (ANC) of less than 1,500 per microliter.

4. A platelet count less than 75,000 per microliter.

5. History of severe neonatal encephalopathy, per modified Sarnat including level of
consciousness as stupor/coma, absent spontaneous activity, decerebrate posture,
flaccid tone, absent suck, absent moro, diverted/nonreactive pupils, lack of heart
rate variability, apnea.

6. Subjects, who in the opinion of the investigators, are unable to comply with the
protocol or have specific health concerns that would potentially increase the risk of
participation. Examples of inability to comply include unwillingness to relocate or
travel to a study site, suspected noncompliance with study procedures, behavior that
jeopardizes the safety or security of the data or study staff, and other causes of
inability to comply.

7. Concurrent participation in another investigational drug trial.

8. History of renal disease or evidence of acute kidney injury defined as serum
creatinine greater than 1.5 mg/dL or an increase of at least 0.2-0.3 mg/dL per day.



Age minimum: N/A
Age maximum: 6 Months
Gender: All

Health Condition(s) or Problem(s) studied

Niemann-Pick Disease, Type C

Intervention(s)

Drug: adrabetadex (2-Hydroxypropyl-Beta-Cyclodextrin)

Primary Outcome(s)

Efficacy of adrabetadex (VTS-270) to reduce plasma levels of glycine-conjugated trihydroxycholanic acid ("bile acid biomarker"), an NPC-specific pharmacodynamic biomarker. [Time Frame: Phase 1: 6 weeks; Phase 2: 6 months]

Secondary Outcome(s)

Reduction of liver and/or spleen volumes [Time Frame: Phase 1: 6 weeks; Phase 2: 6 months]

Effect of drug on serum transaminases [Time Frame: Phase 1: 6 weeks; Phase 2: 6 months]

Secondary ID(s)

1U01HD090845-01

201708114

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)