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NCT03887533

Combined Intrathecal and Intravenous VTS-270 Therapy for Liver and Neurological Disease Associated With Niemann-Pick Disease, Type C1

Terminated Phase 1, PHASE2 Results posted Last updated 30 August 2022
What this trial tests

Phase 1, PHASE2 trial testing VTS-270 in Niemann-Pick Disease, Type C1 in 2 participants. Terminated before completion.

Timeline
6 January 2020
Primary endpoint
25 October 2021
25 October 2021

Quick facts

Lead sponsorEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment2
Start date6 January 2020
Primary completion25 October 2021
Estimated completion25 October 2021
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

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

Who can join

Adults 3 to 60, any sex, with Niemann-Pick Disease, Type C1. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Participants With Adverse Events by Grade Primary · 18 months

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

Grade 1
GroupValue95% CI
VTS-270 at 500 mg/kg1
VTS-270 at 1000 mg/kg1
Grade 2
GroupValue95% CI
VTS-270 at 500 mg/kg1
VTS-270 at 1000 mg/kg1
Grade 3
GroupValue95% CI
VTS-270 at 500 mg/kg0
VTS-270 at 1000 mg/kg0
Grade 4
GroupValue95% CI
VTS-270 at 500 mg/kg0
VTS-270 at 1000 mg/kg0
Grade 5
GroupValue95% CI
VTS-270 at 500 mg/kg0
VTS-270 at 1000 mg/kg0
Participants With Reduction in Plasma Cholestane-3β Primary · Assessed at baseline and at 52 weeks

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

GroupValue95% CI
VTS-270 at 500 mg/kg1
VTS-270 at 1000 mg/kg0
Participants With Reduction in Plasma Bile Acid B (5α) Primary · Assessed at baseline and at 52 weeks

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

GroupValue95% CI
VTS-270 at 500 mg/kg1
VTS-270 at 1000 mg/kg0
Participants With Reduction in C-Triol (6β-triol) Primary · Assessed at baseline and at 52 weeks

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

GroupValue95% CI
VTS-270 at 500 mg/kg1
VTS-270 at 1000 mg/kg0
Participants With Reduction in Liver Stiffness (kPa) Secondary · Assessed at baseline and at 52 weeks

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)

GroupValue95% CI
VTS-270 at 500 mg/kg0
VTS-270 at 1000 mg/kg0
Participants With Reduction in Alanine Aminotransferase Level Secondary · Assessed at baseline and at 52 weeks

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)

GroupValue95% CI
VTS-270 at 500 mg/kg0
VTS-270 at 1000 mg/kg0
Participants With Reduction in Aspartate Aminotransferase Secondary · Assessed at baseline and at 52 weeks

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

GroupValue95% CI
VTS-270 at 500 mg/kg1
VTS-270 at 1000 mg/kg1

Adverse events — posted to ClinicalTrials.gov

Time frame: 18 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

VTS-270 at 500 mg/kg
Serious: 1/1 (100%)
Deaths: 0/1
VTS-270 at 1000 mg/kg
Serious: 0/1 (0%)
Deaths: 0/1

Serious adverse events (1 terms)

ReactionSystemVTS-270 at 500 mg/kgVTS-270 at 1000 mg/kg
Back painMusculoskeletal and connective tissue disorders
Other adverse events (28 terms — click to expand)

ReactionSystemVTS-270 at 500 mg/kgVTS-270 at 1000 mg/kg
EosinophiliaBlood and lymphatic system disorders
AnaemiaBlood and lymphatic system disorders
DizzinessCardiac disorders
FlatulenceGastrointestinal disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
HypothermiaGeneral disorders
HyperthermiaGeneral disorders
Activated partial thromboplastin timeInvestigations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
Lymphocyte count decreasedInvestigations
Platelet count decreasedInvestigations
White blood cell count decreasedInvestigations
HypermagnesaemiaMetabolism and nutrition disorders
HyperphosphataemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Sensory disturbanceNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
RhinitisRespiratory, thoracic and mediastinal disorders
Skin ulcerSkin and subcutaneous tissue disorders
HypertensionVascular disorders
HypotensionVascular disorders
HaematuriaVascular disorders

Most-reported serious reactions: Back pain.

Data from ClinicalTrials.gov NCT03887533 adverse events section.

Sponsor's own description

Background: For people who have Niemann-Pick disease, type C1 (NPC1), cholesterol and other fats have trouble moving out of liver and other tissue cells. This makes the cells sick. Researchers want to find out if a drug called VTS-270 can help. Objective: To test if VTS-270 is safe and effective in treating chronic liver disease associated with NPC1. Eligibility: People ages 3-60 with NPC1 Design: Participants may be screened by phone or under another protocol. Participants will have visits once a month for 12 months. If they have intrathecal injections, the study may last 15 months or more. The first visit will last about 5 days. Others will last 2-3 days. Participants will get VTS-270 injected into a vein at each visit. They can also choose to have intrathecal injections. These are like spinal taps. Some visits will also include: Physical exam Urine tests Blood tests. A small tube or needle will be inserted into the participants vein to collect blood. The small tube will also be used to give the VTS-270. Hearing tests: For one test, participants will have electrodes taped to their head. These will record brain waves. Breathing tests Ultrasound of abdomen: Sounds waves will take pictures of the participant s body. Chest x-ray: This is a picture of the lungs.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. CNS-Targeting Therapies for Lysosomal Storage Diseases: Current Advances and Challenges.
    Edelmann MJ, Maegawa GHB. · · 2020 · cited 43× · PMID 33304924 · DOI 10.3389/fmolb.2020.559804
  2. Cyclodextrins: Only Pharmaceutical Excipients or Full-Fledged Drug Candidates?
    Kovacs T, Nagy P, Panyi G, Szente L, et al · · 2022 · cited 40× · PMID 36559052 · DOI 10.3390/pharmaceutics14122559
  3. Polymer-based drug delivery systems under investigation for enzyme replacement and other therapies of lysosomal storage disorders.
    Placci M, Giannotti MI, Muro S. · · 2023 · cited 14× · PMID 36657645 · DOI 10.1016/j.addr.2022.114683
  4. A Novel Small <i>NPC1</i> Promoter Enhances AAV-Mediated Gene Therapy in Mouse Models of Niemann-Pick Type C1 Disease.
    Hughes MP, Nelvagal HR, Coombe-Tennant O, Smith D, et al · · 2023 · cited 11× · PMID 37371089 · DOI 10.3390/cells12121619
  5. Dietary plant stanol ester supplementation reduces peripheral symptoms in a mouse model of Niemann-Pick type C1 disease.
    Magro Dos Reis I, Houben T, Oligschläger Y, Bücken L, et al · · 2020 · cited 8× · PMID 32291331 · DOI 10.1194/jlr.ra120000632
  6. Delineation of metabolic responses of Npc1<sup>-/-nih</sup> mice lacking the cholesterol-esterifying enzyme SOAT2 to acute treatment with 2-hydroxypropyl-β-cyclodextrin.
    Ramirez CM, Taylor AM, Lopez AM, Repa JJ, et al · · 2020 · cited 5× · PMID 32890578 · DOI 10.1016/j.steroids.2020.108725

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