Trial Outcomes & Findings for Combined Intrathecal and Intravenous VTS-270 Therapy for Liver and Neurological Disease Associated With Niemann-Pick Disease, Type C1 (NCT NCT03887533)
NCT ID: NCT03887533
Last Updated: 2022-08-30
Results Overview
Adverse events (AEs) were used to determine safety and assess safety of intravenous VTS-270 in subjects with Niemann-Pick Disease, type C1. Assessment of safety was made by evaluation of summary statistics of adverse events and unanticipated problems. AEs were assessed using CTCAE version 5.0 grades 1-5. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL\*. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL\*\*. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE
TERMINATED
PHASE1/PHASE2
2 participants
18 months
2022-08-30
Participant Flow
Participant milestones
| Measure |
VTS-270 at 500 mg/kg
Participant received dose of 500 mg/kg of intravenous VTS-270 administered over 2 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
VTS-270 at 1000 mg/kg
Participant received 1000 mg/kg of intravenous VTS-270 over 4 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
|---|---|---|
|
Overall Study
STARTED
|
1
|
1
|
|
Overall Study
COMPLETED
|
1
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Combined Intrathecal and Intravenous VTS-270 Therapy for Liver and Neurological Disease Associated With Niemann-Pick Disease, Type C1
Baseline characteristics by cohort
| Measure |
VTS-270 at 500 mg/kg
n=1 Participants
Participant received dose of 500 mg/kg of intravenous VTS-270 administered over 2 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
VTS-270 at 1000 mg/kg
n=1 Participants
Participant received 1000 mg/kg of intravenous VTS-270 over 4 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
Total
n=2 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
1 participants
n=93 Participants
|
1 participants
n=4 Participants
|
2 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 18 monthsPopulation: All participants who completed the study
Adverse events (AEs) were used to determine safety and assess safety of intravenous VTS-270 in subjects with Niemann-Pick Disease, type C1. Assessment of safety was made by evaluation of summary statistics of adverse events and unanticipated problems. AEs were assessed using CTCAE version 5.0 grades 1-5. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL\*. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL\*\*. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE
Outcome measures
| Measure |
VTS-270 at 500 mg/kg
n=1 Participants
Participant received dose of 500 mg/kg of intravenous VTS-270 administered over 2 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
VTS-270 at 1000 mg/kg
n=1 Participants
Participant received 1000 mg/kg of intravenous VTS-270 over 4 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
|---|---|---|
|
Participants With Adverse Events by Grade
Grade 2
|
1 Participants
|
1 Participants
|
|
Participants With Adverse Events by Grade
Grade 1
|
1 Participants
|
1 Participants
|
|
Participants With Adverse Events by Grade
Grade 3
|
0 Participants
|
0 Participants
|
|
Participants With Adverse Events by Grade
Grade 4
|
0 Participants
|
0 Participants
|
|
Participants With Adverse Events by Grade
Grade 5
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Assessed at baseline and at 52 weeksPopulation: All participants who completed the study
Efficacy of IV VTS-270 in treating chronic liver disease associated with Niemann-Pick Disease, type C1 as measured by reduction in plasma cholestane-3β, an NPC1-specific pharmacodynamic biomarker
Outcome measures
| Measure |
VTS-270 at 500 mg/kg
n=1 Participants
Participant received dose of 500 mg/kg of intravenous VTS-270 administered over 2 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
VTS-270 at 1000 mg/kg
n=1 Participants
Participant received 1000 mg/kg of intravenous VTS-270 over 4 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
|---|---|---|
|
Participants With Reduction in Plasma Cholestane-3β
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Assessed at baseline and at 52 weeksPopulation: All participants who completed the study
Efficacy of IV VTS-270 in treating chronic liver disease associated with Niemann-Pick Disease, type C1 as measured by reduction in bile acid B (5α), an NPC1-specific pharmacodynamic biomarker
Outcome measures
| Measure |
VTS-270 at 500 mg/kg
n=1 Participants
Participant received dose of 500 mg/kg of intravenous VTS-270 administered over 2 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
VTS-270 at 1000 mg/kg
n=1 Participants
Participant received 1000 mg/kg of intravenous VTS-270 over 4 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
|---|---|---|
|
Participants With Reduction in Plasma Bile Acid B (5α)
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Assessed at baseline and at 52 weeksPopulation: All participants who completed the study
Efficacy of IV VTS-270 in treating chronic liver disease associated with Niemann-Pick Disease, type C1 as measured by reduction in C-Triol (6β-triol), an NPC1-specific pharmacodynamic biomarker
Outcome measures
| Measure |
VTS-270 at 500 mg/kg
n=1 Participants
Participant received dose of 500 mg/kg of intravenous VTS-270 administered over 2 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
VTS-270 at 1000 mg/kg
n=1 Participants
Participant received 1000 mg/kg of intravenous VTS-270 over 4 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
|---|---|---|
|
Participants With Reduction in C-Triol (6β-triol)
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Assessed at baseline and at 52 weeksPopulation: All participants who completed the study
Efficacy of IV VTS-270 in treating chronic liver disease associated with Niemann-Pick Disease, type C1 as measured by reduction in liver stiffness (kPa)
Outcome measures
| Measure |
VTS-270 at 500 mg/kg
n=1 Participants
Participant received dose of 500 mg/kg of intravenous VTS-270 administered over 2 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
VTS-270 at 1000 mg/kg
n=1 Participants
Participant received 1000 mg/kg of intravenous VTS-270 over 4 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
|---|---|---|
|
Participants With Reduction in Liver Stiffness (kPa)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Assessed at baseline and at 52 weeksPopulation: All participants who completed the study
Efficacy of IV VTS-270 in treating chronic liver disease associated with Niemann-Pick Disease, type C1 as measured by reduction of serum alanine aminotransferase level (ALT)
Outcome measures
| Measure |
VTS-270 at 500 mg/kg
n=1 Participants
Participant received dose of 500 mg/kg of intravenous VTS-270 administered over 2 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
VTS-270 at 1000 mg/kg
n=1 Participants
Participant received 1000 mg/kg of intravenous VTS-270 over 4 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
|---|---|---|
|
Participants With Reduction in Alanine Aminotransferase Level
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Assessed at baseline and at 52 weeksPopulation: All participants who completed the study
Efficacy of IV VTS-270 in treating chronic liver disease associated with Niemann-Pick Disease, type C1 as measured by reduction of serum aspartate aminotransferase (AST) level
Outcome measures
| Measure |
VTS-270 at 500 mg/kg
n=1 Participants
Participant received dose of 500 mg/kg of intravenous VTS-270 administered over 2 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
VTS-270 at 1000 mg/kg
n=1 Participants
Participant received 1000 mg/kg of intravenous VTS-270 over 4 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
|---|---|---|
|
Participants With Reduction in Aspartate Aminotransferase
|
1 Participants
|
1 Participants
|
Adverse Events
VTS-270 at 500 mg/kg
VTS-270 at 1000 mg/kg
Serious adverse events
| Measure |
VTS-270 at 500 mg/kg
n=1 participants at risk
Participant received dose of 500 mg/kg of intravenous VTS-270 administered over 2 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
VTS-270 at 1000 mg/kg
n=1 participants at risk
Participant received 1000 mg/kg of intravenous VTS-270 over 4 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Back pain
|
100.0%
1/1 • Number of events 1 • 18 months
|
0.00%
0/1 • 18 months
|
Other adverse events
| Measure |
VTS-270 at 500 mg/kg
n=1 participants at risk
Participant received dose of 500 mg/kg of intravenous VTS-270 administered over 2 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
VTS-270 at 1000 mg/kg
n=1 participants at risk
Participant received 1000 mg/kg of intravenous VTS-270 over 4 hours monthly for 12 months. Participant also received 900 mg intrathecal VTS-270 therapy monthly for 18 months.
|
|---|---|---|
|
Blood and lymphatic system disorders
Eosinophilia
|
0.00%
0/1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Blood and lymphatic system disorders
Anaemia
|
100.0%
1/1 • Number of events 1 • 18 months
|
0.00%
0/1 • 18 months
|
|
Cardiac disorders
Dizziness
|
100.0%
1/1 • Number of events 1 • 18 months
|
0.00%
0/1 • 18 months
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Gastrointestinal disorders
Nausea
|
100.0%
1/1 • Number of events 1 • 18 months
|
0.00%
0/1 • 18 months
|
|
Gastrointestinal disorders
Vomiting
|
100.0%
1/1 • Number of events 1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
General disorders
Hypothermia
|
0.00%
0/1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
General disorders
Hyperthermia
|
0.00%
0/1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Investigations
Activated partial thromboplastin time
|
100.0%
1/1 • Number of events 1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Investigations
Alanine aminotransferase increased
|
100.0%
1/1 • Number of events 1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Investigations
Aspartate aminotransferase increased
|
100.0%
1/1 • Number of events 1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Investigations
Lymphocyte count decreased
|
100.0%
1/1 • Number of events 1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Investigations
Platelet count decreased
|
100.0%
1/1 • Number of events 1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Investigations
White blood cell count decreased
|
100.0%
1/1 • Number of events 1 • 18 months
|
0.00%
0/1 • 18 months
|
|
Metabolism and nutrition disorders
Hypermagnesaemia
|
0.00%
0/1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
100.0%
1/1 • Number of events 1 • 18 months
|
0.00%
0/1 • 18 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Nervous system disorders
Sensory disturbance
|
100.0%
1/1 • Number of events 1 • 18 months
|
0.00%
0/1 • 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis
|
100.0%
1/1 • Number of events 1 • 18 months
|
0.00%
0/1 • 18 months
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
100.0%
1/1 • Number of events 1 • 18 months
|
0.00%
0/1 • 18 months
|
|
Vascular disorders
Hypertension
|
100.0%
1/1 • Number of events 1 • 18 months
|
100.0%
1/1 • Number of events 1 • 18 months
|
|
Vascular disorders
Hypotension
|
100.0%
1/1 • Number of events 1 • 18 months
|
0.00%
0/1 • 18 months
|
|
Vascular disorders
Haematuria
|
100.0%
1/1 • Number of events 1 • 18 months
|
0.00%
0/1 • 18 months
|
Additional Information
Dr. Forbes Porter
National Institute of Child Health and Human Development (NICHD)
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place