Trial Outcomes & Findings for Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C (NCT NCT03471143)
NCT ID: NCT03471143
Last Updated: 2026-01-05
Results Overview
This bile acid, 5α-cholanic acid-3β, 5α, 6β-triol N-(carboxymethyl)-amide, is elevated \>99% of NPC1 subjects, is largely generated in the liver and therefore provides a biochemical measure of oxidizable lysosomal unesterified cholesterol in liver tissue. The primary outcome measure in phase 1 of the study is the change in plasma levels of 5α-cholanic acid-3β, 5α, 6β-triol N-(carboxymethyl)-amide measured in nanograms/ml from baseline to 6 weeks. The primary outcome measure in phase 2 of the study is the change in plasma levels of 5α-cholanic acid-3β, 5α, 6β-triol N-(carboxymethyl)-amide measured in nanograms/ml from 6 weeks to the end of the 6 month treatment period.
COMPLETED
PHASE1/PHASE2
4 participants
Phase 1: 6 weeks; Phase 2: 6 months
2026-01-05
Participant Flow
The original enrollment goal was 12 subjects up to maximum of 15 subjects to account for potential study withdrawals, discontinuations or unconfirmed diagnosis of NPC. Six subjects would be studied at each dose level. Cohort 1: Subjects 1-6 500mg/kg Cohort 2: Subjects 7-12 1000mg/kg The four subjects enrolled received 500mg/kg study drug.
Participant milestones
| Measure |
IV Adrabetadex (VTS-270) for NPC1 Infants
Treatment group dosing was 500mg intravenous adrabetatex twice a week for 6 weeks, then received 500mg intravenous adrabetatex monthly for 6 months.
|
|---|---|
|
Overall Study
STARTED
|
4
|
|
Overall Study
COMPLETED
|
3
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C
Baseline characteristics by cohort
| Measure |
IV Adrabetadex (VTS-270) for NPC1 Infants
n=4 Participants
IV Adrabetadex (VTS-270) for NPC1 Infants. Will measure plasma level of 5α-cholanic acid-3β, 5α, 6β-triol N-(carboxymethyl)-amide.
|
|---|---|
|
Age, Categorical
<=18 years
|
4 Participants
n=9667 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=9667 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=9667 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=9667 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=9667 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=9667 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=9667 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=9667 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=9667 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=9667 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=9667 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=9667 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=9667 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=9667 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=9667 Participants
|
|
Plasma level of 5α-cholanic acid-3β, 5α, 6β-triol N-(carboxymethyl)-amide
|
120.6 ng/ml
n=9667 Participants
|
|
Aspartate aminotransferase (AST)
|
168 U/L
n=9667 Participants
|
|
Alanine transaminase (ALT)
|
158.5 U/L
n=9667 Participants
|
|
Spleen volume
|
86.3 cc
n=9667 Participants
|
PRIMARY outcome
Timeframe: Phase 1: 6 weeks; Phase 2: 6 monthsPopulation: One of the participants only had baseline measurement.
This bile acid, 5α-cholanic acid-3β, 5α, 6β-triol N-(carboxymethyl)-amide, is elevated \>99% of NPC1 subjects, is largely generated in the liver and therefore provides a biochemical measure of oxidizable lysosomal unesterified cholesterol in liver tissue. The primary outcome measure in phase 1 of the study is the change in plasma levels of 5α-cholanic acid-3β, 5α, 6β-triol N-(carboxymethyl)-amide measured in nanograms/ml from baseline to 6 weeks. The primary outcome measure in phase 2 of the study is the change in plasma levels of 5α-cholanic acid-3β, 5α, 6β-triol N-(carboxymethyl)-amide measured in nanograms/ml from 6 weeks to the end of the 6 month treatment period.
Outcome measures
| Measure |
IV Adrabetadex (VTS-270) for NPC1 Infants
n=3 Participants
In this Phase 1/2a open label trial, there was only 1 arm for treatment, with no comparison group. There was no dose escalation. All participants received 500 mg/kg.adrabetadex (2-Hydroxypropyl-Beta-Cyclodextrin). In Phase 1: Dosing frequency was twice a week administered via a peripherally inserted central catheter (PICC) for six weeks up to a total of 12 administrations.
Subjects who demonstrated significant reduction either in the glycine-conjugated trihydroxycholanic acid biomarker or serum bilirubin (direct bilirubin or direct bilirubin:total bilirubin ratio) were allowed to crossover into the second phase of the study, an open-label phase of six months duration. In the this phase of the study, dosing frequency was monthly with IV VTS-270 administered via peripheral IV access for six months for a total of six administrations.
|
|---|---|
|
Efficacy of Adrabetadex (VTS-270) to Reduce Plasma Levels of a Conjugated Bile Acid, Known as 5α-cholanic Acid-3β, 5α, 6β-triol N-(Carboxymethyl)-Amide
6 weeks
|
32.6 ng/ml
Interval 10.5 to 129.0
|
|
Efficacy of Adrabetadex (VTS-270) to Reduce Plasma Levels of a Conjugated Bile Acid, Known as 5α-cholanic Acid-3β, 5α, 6β-triol N-(Carboxymethyl)-Amide
6 months
|
87.9 ng/ml
Interval 46.6 to 101.0
|
SECONDARY outcome
Timeframe: Phase 1: 6 weeks; Phase 2: 6 monthsPopulation: One of the participants only had baseline measurement.
Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) are elevated with liver dysfunction. The outcome measure in phase 1 of the study is the change in ALT and AST levels from baseline to 6 weeks. The outcome measure in phase 2 of the study is the change in ALT and AST levels from 6 weeks to the end of the 6 month treatment period.
Outcome measures
| Measure |
IV Adrabetadex (VTS-270) for NPC1 Infants
n=3 Participants
In this Phase 1/2a open label trial, there was only 1 arm for treatment, with no comparison group. There was no dose escalation. All participants received 500 mg/kg.adrabetadex (2-Hydroxypropyl-Beta-Cyclodextrin). In Phase 1: Dosing frequency was twice a week administered via a peripherally inserted central catheter (PICC) for six weeks up to a total of 12 administrations.
Subjects who demonstrated significant reduction either in the glycine-conjugated trihydroxycholanic acid biomarker or serum bilirubin (direct bilirubin or direct bilirubin:total bilirubin ratio) were allowed to crossover into the second phase of the study, an open-label phase of six months duration. In the this phase of the study, dosing frequency was monthly with IV VTS-270 administered via peripheral IV access for six months for a total of six administrations.
|
|---|---|
|
Effect of Drug on Serum Transaminases
ALT 6 weeks
|
87 U/L
Interval 80.0 to 203.0
|
|
Effect of Drug on Serum Transaminases
AST 6 weeks
|
114 U/L
Interval 86.0 to 293.0
|
|
Effect of Drug on Serum Transaminases
ALT 6 months
|
65 U/L
Interval 48.0 to 71.0
|
|
Effect of Drug on Serum Transaminases
AST 6 months
|
77 U/L
Interval 75.0 to 89.0
|
SECONDARY outcome
Timeframe: Phase 1: 6 weeks; Phase 2: 6 monthsPopulation: We were only able to collect spleen volume data due to the radiologist reporting they could not accurately obtain liver volume data. The contact radiologist for this protocol has left the institution, stopping any additional work on liver ultrasound volumes. None of the remaining radiology colleagues had time to bring forward. Liver volumes will never be obtained for this measure in the future.
Abdominal ultrasound. The outcome measure in phase 1 of the study is the change in liver and/or spleen volumes from baseline to 6 weeks. The outcome measure in phase 2 of the study is the change in liver and/or spleen volumes from 6 weeks to the end of the 6 month treatment period. We were only able to collect spleen volume data due to the radiologist reporting they could not accurately obtain liver volume data. The contact radiologist for this protocol has left the institution, stopping any additional work on liver ultrasound volumes. None of the remaining radiology colleagues had time to bring forward. Liver volumes will never be obtained for this measure in the future.
Outcome measures
| Measure |
IV Adrabetadex (VTS-270) for NPC1 Infants
n=3 Participants
In this Phase 1/2a open label trial, there was only 1 arm for treatment, with no comparison group. There was no dose escalation. All participants received 500 mg/kg.adrabetadex (2-Hydroxypropyl-Beta-Cyclodextrin). In Phase 1: Dosing frequency was twice a week administered via a peripherally inserted central catheter (PICC) for six weeks up to a total of 12 administrations.
Subjects who demonstrated significant reduction either in the glycine-conjugated trihydroxycholanic acid biomarker or serum bilirubin (direct bilirubin or direct bilirubin:total bilirubin ratio) were allowed to crossover into the second phase of the study, an open-label phase of six months duration. In the this phase of the study, dosing frequency was monthly with IV VTS-270 administered via peripheral IV access for six months for a total of six administrations.
|
|---|---|
|
Reduction of Liver and/or Spleen Volumes
6 weeks
|
71.8 cc
Interval 58.6 to 98.1
|
|
Reduction of Liver and/or Spleen Volumes
6 months
|
127 cc
Interval 69.2 to 177.2
|
Adverse Events
IV Adrabetadex (VTS-270) for NPC1 Infants
Serious adverse events
| Measure |
IV Adrabetadex (VTS-270) for NPC1 Infants
n=4 participants at risk
Phase 1: Dosing frequency will be twice a week administered via a peripherally inserted central catheter (PICC) for six weeks for a total of 12 administrations. Doses 3-12 will occur as an outpatient.
Doses to be studied are 500, and 1000 mg/kg. Six subjects will be studied at each dose level. Cohort 1: Subjects 1-6 will receive 500 mg/kg Cohort 2: Subjects 7-12 will receive 1000 mg/kg Subjects who demonstrate significant reduction either in the glycine-conjugated trihydroxycholanic acid biomarker or serum bilirubin (direct bilirubin or direct bilirubin:total bilirubin ratio) will be allowed to crossover into the second phase of the study, an open-label phase of six months duration. In the this phase of the study, dosing frequency will be monthly with IV VTS-270 administered via peripheral IV access for six months for a total of six administrations.
adrabetadex (2-Hydroxypropyl-Beta-Cyclodextrin): VTS-270 (2-Hydroxypropyl-Beta-Cyclodextrin) will be administered intravenously to specifically target liver disease. In the first phase of the study, dosing frequency will be twice a week with IV adrabetadex (VTS-270) for six weeks for a total of 12 administrations. Subjects will be evaluated at each study visit for evidence of adverse effects.
Doses to be studied are 500, and 1000 mg/kg. Six subjects will be studied at each dose level. Cohort 1: Subjects 1-6, 500 mg/kg Cohort 2: Subjects 7-12, 1000 mg/kg
|
|---|---|
|
Hepatobiliary disorders
Death
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Infections and infestations
Hospitalization
|
75.0%
3/4 • 7 months and 2 weeks
|
Other adverse events
| Measure |
IV Adrabetadex (VTS-270) for NPC1 Infants
n=4 participants at risk
Phase 1: Dosing frequency will be twice a week administered via a peripherally inserted central catheter (PICC) for six weeks for a total of 12 administrations. Doses 3-12 will occur as an outpatient.
Doses to be studied are 500, and 1000 mg/kg. Six subjects will be studied at each dose level. Cohort 1: Subjects 1-6 will receive 500 mg/kg Cohort 2: Subjects 7-12 will receive 1000 mg/kg Subjects who demonstrate significant reduction either in the glycine-conjugated trihydroxycholanic acid biomarker or serum bilirubin (direct bilirubin or direct bilirubin:total bilirubin ratio) will be allowed to crossover into the second phase of the study, an open-label phase of six months duration. In the this phase of the study, dosing frequency will be monthly with IV VTS-270 administered via peripheral IV access for six months for a total of six administrations.
adrabetadex (2-Hydroxypropyl-Beta-Cyclodextrin): VTS-270 (2-Hydroxypropyl-Beta-Cyclodextrin) will be administered intravenously to specifically target liver disease. In the first phase of the study, dosing frequency will be twice a week with IV adrabetadex (VTS-270) for six weeks for a total of 12 administrations. Subjects will be evaluated at each study visit for evidence of adverse effects.
Doses to be studied are 500, and 1000 mg/kg. Six subjects will be studied at each dose level. Cohort 1: Subjects 1-6, 500 mg/kg Cohort 2: Subjects 7-12, 1000 mg/kg
|
|---|---|
|
Hepatobiliary disorders
elevated alkaline phosphatase
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Renal and urinary disorders
bilirubin +1 in urine
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Respiratory, thoracic and mediastinal disorders
intermittent stridor
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Nervous system disorders
decreased muscle tone in extremities
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Musculoskeletal and connective tissue disorders
diastasis recti
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Nervous system disorders
head lag
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Nervous system disorders
Horner Syndrome
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Hepatobiliary disorders
increased hepatomegaly
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Hepatobiliary disorders
increased splenomegaly
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Eye disorders
dacryostenosis, left eye
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Hepatobiliary disorders
increased GGT
|
25.0%
1/4 • Number of events 2 • 7 months and 2 weeks
|
|
Gastrointestinal disorders
Sandifer syndrome
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Hepatobiliary disorders
increased AST
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Hepatobiliary disorders
increased ALT
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Infections and infestations
fever
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Infections and infestations
viral exthanthem
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Metabolism and nutrition disorders
hypernatremia
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Metabolism and nutrition disorders
hypokalemia
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Metabolism and nutrition disorders
hyperkalemia
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Renal and urinary disorders
increased BUN
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Blood and lymphatic system disorders
anemia
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Blood and lymphatic system disorders
platelet count decreased
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Renal and urinary disorders
hematuria
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Skin and subcutaneous tissue disorders
dry skin and maculopapular rash on both cheeks
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Hepatobiliary disorders
elevated prothrombin time
|
50.0%
2/4 • Number of events 2 • 7 months and 2 weeks
|
|
Skin and subcutaneous tissue disorders
diaper rash
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Cardiac disorders
right ventricular hypertrophy on ECG
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Nervous system disorders
mild truncal hypotonia
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Vascular disorders
oozing around PICC line-blood
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Respiratory, thoracic and mediastinal disorders
occasional cough and nasal congestion
|
50.0%
2/4 • Number of events 2 • 7 months and 2 weeks
|
|
Nervous system disorders
ankle clonus
|
50.0%
2/4 • Number of events 2 • 7 months and 2 weeks
|
|
Nervous system disorders
increased patellar reflexes
|
50.0%
2/4 • Number of events 2 • 7 months and 2 weeks
|
|
Respiratory, thoracic and mediastinal disorders
upper respiratory infection
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
Eye disorders
limited vertical gaze
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
|
General disorders
small umbilical hernia
|
50.0%
2/4 • Number of events 2 • 7 months and 2 weeks
|
|
Cardiac disorders
1/6 systolic murmur
|
25.0%
1/4 • Number of events 1 • 7 months and 2 weeks
|
Additional Information
Dr. Patricia Dickson
Washington University School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place