Phase 3 N=12 Randomized Double-blind Treatment

VTS-270 to Treat Niemann-Pick Type C1 (NPC1) Disease

Niemann-Pick Disease, Type C

Bottom Line

View on ClinicalTrials.gov: NCT02534844 ↗

Enrolled (actual)

Serious AEs

39.3%

Results posted

Feb 2023

Primary outcome: Primary: Parts A/B: Change From Baseline to Week 52 in 4-Item Composite Score of Niemann Pick Type C Severity Scale (NPC-SS) Score — 8.1; 8.8; -0.1; 0.0 score on a scale

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Parts A/B: Adrabetadex (Drug); Parts A/B: Sham Control (Other)
Age: Pediatric, Adult · 4+ yrs
Sex: All
Sponsor: Mandos LLC
Primary completion: Mar 2018

Outcome Measures

Outcome	Result	p-value
PRIMARY Parts A/B: Change From Baseline to Week 52 in 4-Item Composite Score of Niemann Pick Type C Severity Scale (NPC-SS) Score	8.1; 8.8; -0.1; 0.0	—
PRIMARY Parts A/B: Number of Participants Classified With Each Score on the Clinician Global Impression of Change (CGIC) at Week 52	0; 0; 1; 5; 4; 9	—
SECONDARY Parts A/B: Change From Baseline to Week 52 in NPC-SS Total Score (Excluding Hearing and Auditory Brainstem Response [ABR])	16.94; 17.81; -0.74; -0.34	—
SECONDARY Parts A/ B: Number of Participants Classified as CGIC Responders at Week 52	7; 23	—
SECONDARY Parts A/B: Number of Participants Classified as Responders on NPC-SS Total Score (Excluding Hearing and ABR) at Week 52	13; 22	—
SECONDARY Parts A/B: EQ-5D-3L Questionnaire Visual Analog Scale (VAS) Score (for Health Status) at Baseline and at Week 52	71.9; 68.3; 73.2; 75.7	—
SECONDARY Parts A/B: Number of Participants Treated for at Least 6 Months Who Qualified for the Rescue Option	2; 2	—
SECONDARY Parts A/B: Change From Baseline to Week 52 in Each of the 9 Clinical Domains of the NPC-SS	1.83; 2.21; 0.00; 0.06; 2.06; 2.16	—
SECONDARY Parts A/B: Change From Baseline to Week 52 in the Total NPC-SS (With Hearing Domain and ABR Modifier Included)	15.64; 17.76; 0.000; 0.75	—
SECONDARY Parts A/B: Time to One Point Increase (Worsening) in NPC-SS Composite Score	118; 169	—
SECONDARY Parts A/B: Change From Baseline in the Timed Up and Go (TUG) Test at Week 52	18.04; 16.40; 0.86; 2.70	—
SECONDARY Parts A/B: Change From Baseline in the 9-Hole Peg Test at Week 52	-1.49; -1.79	—
SECONDARY Parts A/B: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	3; 3; 3; 3; 28; 14	—
SECONDARY Parts A/B: Change From Baseline to Week 52 in Mean Annualized Rate of Change (Slope) of NPC-SS Composite Score	-0.05; 0.08	—

Summary

Due to different study designs, the sponsor separated Part C into a separate registration (NCT04958642), leaving Parts A/B here in NCT02534844. This study is to find out how safe and effective VTS-270 is for patients with Niemann-Pick Type C1 (NPC1) disease who have neurologic symptoms (listed under Keywords). In Parts A/B, two out of every three patients will receive the study drug. The third patient will receive 1 to 2 small needle pricks at the location where the LP and IT injection is normally made (sham control). In Part C, all participants will receive study drug, as described in the Part C registration record. Start date for this record is the first day a participant was enrolled in Parts A/B. The trial is actually continuing until the last primary outcome measure of safety data are collected from Part C participants. The last primary outcome measure of safety, along with final adverse events results will be posted in the separate Part C registration record.

Eligibility Criteria

Key Inclusion Criteria

Parts A/B:

Had onset of neurological symptoms prior to 15 years of age
Has confirmed diagnosis of NPC1 determined by either:
two NPC1 mutations
positive filipin staining and at least one NPC1 mutation
vertical supranuclear gaze palsy (VSNGP) in combination with either: one NPC1 mutation, OR positive filipin staining or oxysterol levels consistent with NPC disease and no Niemann-Pick Type C2 (NPC2) Disease mutations
Adult participant or parent/guardian has provided written informed consent, with assent collected from minors of appropriate age
Is able to undergo a lumbar puncture (LP) and IT drug administration under conscious sedation or general anesthesia
Has an NPC Clinical Severity Scale Score of 1 through 4, inclusive, in two or more of the following components: ambulation, fine motor skills, or swallowing; and has a score of 0 through 4 on the cognition component
Has a total NPC Clinical Severity Scale Score of 10 or greater
If taking miglustat, must have been on a stable dose for past 6-8 weeks and be willing to remain on a stable dose
If participant has seizures, they have been adequately controlled for 3 months without changing dose or regimen
Has agreed to discontinue all non-prescription supplements at least 1 month prior to first dose (Study Day 0)
Has agreed to discontinue any other investigational treatments for NPC including vorinostat or arimoclomol at least 3 months prior to first dose (Study Day 0)
If of child-bearing potential (not surgically sterile), agrees to use a medically acceptable method continuously, until at least 30 days after participation in the study

Key Exclusion Criteria

Has exclusion criteria as assessed by NPC Clinical Severity Scale:
Unable to walk, wheelchair dependent (ambulation NPC score=5)
Has need for a nasogastric tube to overcome swallowing difficulties (swallowing NPC score=5) unless used for supplemental feeding or administering medication
severe dysmetria (fine motor score =5) or
minimal cognitive function (cognition NPC score=5)
Weighs less than 15 kg
Has had prior treatment with intravenous 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) for NPC1 disease, unless the subject has undergone a minimum 3-month washout period prior to Study Day 0, or has had any prior intrathecal (IT) administration of HP-β-CD
Is taking antipsychotics for treatment of psychosis; use of antipsychotic medication for treatment of other disorders (e.g., Attention Deficit Hyperactivity Disorder) will not exclude participation in this trial
Has a history of hypersensitivity reactions to any product containing HP-β-CD
Has a spinal deformity that could impact the ability to perform a lumbar puncture
Has had a skin infection in the lumbar region within 2 months of study entry
Has neutropenia, defined as an absolute neutrophil count (ANC) of less than 1.5 X 10^9/L
Has thrombocytopenia (platelet count of less than 75 X 10^9/L)
Has activated partial thromboplastin time (aPTT) or prothrombin time (PT) prolonged by > 1.5 times the upper limit of normal (ULN) or known history of a bleeding disorder
Has had status epilepticus occurring within 3 months of screening and/or seizure frequency that cannot be quantified
Has evidence of either obstructive hydrocephalus or normal pressure hydrocephalus
Has recently used anticoagulants [in past 2 weeks prior to first dose (Study Day 0); re: lumbar puncture safety].
Is unable to comply with the study procedures or has a clinical disease or laboratory abnormality that in the opinion of the investigator would potentially increase the risk of participation

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02534844). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.