Niemann-Pick Type C Treatment With Adrabetadex for Symptoms of Brain and Nervous System

Open-label Evaluation of Adrabetadex in Patients With Neurologic Manifestations of Niemann-Pick Type C Disease (NPC)

This study was amended from expanded access to a clinical trial. Information will be collected about long-term safety and effectiveness of adrabetadex shots in the spine every 2 weeks.

Participants who were already taking adrabetadex will receive their stable dose. Participants who have not ever taken it will start by receiving 400 mg.

Participants will receive treatment every 2 weeks until their doctor finds it does not help them anymore, they withdraw, or the study is stopped for any reason. Participants will not receive additional study treatment after their participation in this protocol.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas System
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health System
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Rare Disease Research, LLC
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Gillette Children's Specialty Healthcare
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Children's Specialty Center of Nevada
  • New York
    • New York, New York, United States, 10017
      • NYU Langone Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • The Children's Hospital at TriStar Centennial
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center of Central Texas
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Carilion Medical Center, Carilion Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

To be included in the study, a participant must meet the following criteria:

• Is male or female and at least 4 years of age at time of screening.
• Has a confirmed diagnosis of NPC and exhibits neurologic symptoms.
• Has written informed consent/assent to participate.
• Has the ability to undergo LP and IT drug administration.
• If taking miglustat (Zavesca®), must have been on a stable dose for the past 6 weeks and be willing to remain on a stable dose for the duration of participation in the study, or discontinue miglustat use at least 6 weeks before entry into the study (Day 1).
• If has a history of seizures, the condition is adequately controlled as per protocol requirements.
• Agrees to discontinue any investigational treatments (other than adrabetadex) for at least 1 month before first dose on Day 1.
• If engaging in heterosexual sex, agrees to use a protocol-defined method of contraception throughout the study, and until 30 days after completing the study.
• Has a responsible adult who the investigator determines is able and willing to comply with study requirements and a parent/guardian who will accompany the participant to study visits.

Exclusion Criteria:

Participants will be excluded from the study if they meet any of the following criteria:

• Weighs less than 15 kg.
• Has a history of hypersensitivity reactions to any product containing 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) or has a history of hypersensitivity reactions or allergy to anesthesia/sedation.
• Has received treatment with any investigational product (other than adrabetadex) within 1 month prior to Day 1 of treatment.
• Is pregnant or nursing.
• Has systemic infection or uncontrolled psychosis.
• Has known history of a bleeding disorder.
• Has used anticoagulants within 2 months of entry into the study.

• Per protocol, or in the opinion of the investigator:

  1. has laboratory values that would preclude participation
  2. has suspected infection of the central nervous system (CNS)
  3. has a spinal deformity that could impact performance of repeated LPs
  4. has a serious skin infection in the lumbar region or evidence of obstructive or normal pressure hydrocephalus
  5. is unable to comply with the study requirements
  6. has a medical condition that might increase the risk of participation

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; Participants will receive prescribed adrabetadex by intra-thecal (IT) injection every 2 weeks.	Drug: Adrabetadex; Administered via lumbar puncture (LP) and IT infusion; Other Names: VTS-270

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 adverse event (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 Week 134

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2018
• Primary Completion (Actual): November 2, 2021
• Study Completion (Actual): November 2, 2021

Study Registration Dates

• First Submitted: August 19, 2018
• First Submitted That Met QC Criteria: August 19, 2018
• First Posted (Actual): August 23, 2018

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: NPC; Niemann-Pick; NPC Type 1 (NPC1)
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lymphatic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C
• Other Study ID Numbers: VTS-270-001

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