Adrabetadex to Treat Niemann-Pick Type C1 (NPC1) Disease

A Phase 2B/3 Prospective, Randomized, Double-Blind, Sham-Controlled Trial of VTS-270 (2-hydroxypropyl-β-cyclodextrin) in Subjects With Neurologic Manifestations of Niemann-Pick Type C1 (NPC1) Disease

Due to different study designs, the sponsor separated Part C into this separate registration (NCT04958642), leaving Parts A/B in NCT02534844. The trial's final results for the primary outcome measure of Adverse Events (AE) will be reported here.

This study is to evaluate how safe and effective adrabetadex is for participants with Niemann-Pick Type C1 (NPC1) disease who experience neurologic symptoms (listed under Keywords).

In Parts A/B (NCT02534844), two out of every 3 participants will receive the study drug. The third participant will receive 1 to 2 small needle pricks at the location where the IT injection is normally made (sham control).

In Part C, all participants will receive study drug.

Study Overview

• Status: Terminated
• Conditions: Niemann-Pick Disease, Type C
• Intervention / Treatment: Drug: Adrabetadex

Detailed Description

Participants in Part C will receive adrabetadex until the investigator considers adrabetadex to no longer be beneficial to the participant, or the development program is discontinued.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • The Prince of Wales Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
  • Victria
    • Melbourne, Victria, Australia
      • Royal Melbourne Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• France
  • Cedex 12
    • Paris, Cedex 12, France, 75 571
      • CHU Paris Est - Hopital d'Enfants Armand-Trousseau
• Germany
  • Bochum, Germany, 44791
    • Katholisches Klinikim Bochum gGmbH
  • Mainz, Germany, 55131
    • Universitaetsklinikum Mainz
  • Münster, Germany, 48149
    • Universitaetsklinikum Muenster
• New Zealand
  • Hamilton, New Zealand, 3204
    • Waikato Hospital
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital (Singapore) Pte, Ltd
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, Universitätsspital Bern
• Turkey
  • Ankara, Turkey
    • Gazi University Medical Faculty
  • Ankara, Turkey
    • Hacettepe University Medical Faculty
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital NHS Foundation Trust
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Orange, California, United States, 92867
      • Children's Hospital of Orange County: CHOC Children's
    • San Francisco, California, United States, 94143-0780
      • University of California San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Gainesville, Florida, United States, 32608
      • Shands Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Maryland
    • Bethesda, Maryland, United States, 20892-2425
      • Eunice Kennedy Shriver National Institute of Child Health and Human Development
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18101
      • Lehigh Valley Health Network
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center of Central Texas
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

One of the following is required for inclusion into VTS301 Part C:

• Has agreed to convert from the monthly dosing regimen used in the NIH phase 1/2a protocol to an every 2 weeks dosing regimen
• The investigator has received prior written authorization from the sponsor for the participant to enter VTS301 Part C on an amended dose and/or regimen
• Has received prior written authorization from Vtesse to enroll directly into Part C

Exclusion criteria:

• None of the inclusion criteria are applicable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adrabetadex; All participants receive their prescribed dose of adrabetadex. Dose is allowed to be adjusted down to a minimum of 400 milligrams (mg) or up to a maximum of 900 mg, at the investigator's discretion.	Drug: Adrabetadex; Mallinckrodt test formulation, administered intrathecal (IT) via lumbar puncture (LP) infusion.; Other Names: VTS-270; 2-hydroxypropyl-β-cyclodextrin; Cyclodextrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A TEAE was defined as an AE with onset on or after the start of adrabetadex treatment. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Baseline up to 5 years

Collaborators and Investigators

• Sponsor: Mandos LLC
• Investigators: Study Director: Clinical Study Lead, Mandos LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2015
• Primary Completion (Actual): April 11, 2022
• Study Completion (Actual): April 11, 2022

Study Registration Dates

• First Submitted: June 29, 2021
• First Submitted That Met QC Criteria: July 1, 2021
• First Posted (Actual): July 12, 2021

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 4, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: pediatrics; cognitive dysfunction; dysphagia; Niemann-Pick Type C1 (NPC1) Disease; neurologic disease; gross motor dysfunction; fine motor dysfunction; swallowing problems; gait abnormalities
• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lymphatic Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Dementia; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Frontotemporal Lobar Degeneration; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Frontotemporal Dementia; Pick Disease of the Brain; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C
• Other Study ID Numbers: VTS301 (Part C); 2015-002548-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No