Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Open-label Study of VTS-270 in Participants With Neurologic Manifestations of Niemann-Pick Type C1

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03879655
Recruitment Status : Not yet recruiting
First Posted : March 19, 2019
Last Update Posted : March 19, 2019
Sponsor:
Information provided by (Responsible Party):
Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company

Brief Summary:
This is a multicenter, multinational, open-label study of to evaluate the long-term safety, tolerability, and efficacy of VTS-270 (2-hydroxypropyl-β-cyclodextrin) in participants transitioning from Study VTS301 in participants with Neurologic Manifestations of Niemann-Pick Type C1 Disease.

Condition or disease Intervention/treatment Phase
Niemann-Pick Disease, Type C Drug: VTS-270 Phase 2 Phase 3

Detailed Description:

Non-clinical studies and a Phase 1 clinical trial suggest that intrathecal administration of VTS-270 in patients with neurologic manifestations of Niemann-Pick Type C1 (NPC1) disease has the potential to slow the rate of progression of their neurologic disease. Niemann-Pick Type C1 (NPC1) disease is a rare, neurodegenerative, inherited, autosomal recessive lysosomal lipid storage disorder primarily in children and teenagers. The disease is characterized by the inability to properly metabolize cholesterol and other lipids within the cell due to mutations in the NPC1 gene causing unesterified cholesterol to accumulate in the brain, liver and spleen.

Eligible participants who transition into this study will receive treatment with VTS-270 at the last dose level administered in Study VTS301, administered IT via LP infusion every 2 weeks, for up to a total duration of 3 years or until the investigator considers VTS-270 to be no longer beneficial to the participant, VTS-270 receives marketing authorization, or the VTS-270 development program is discontinued.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2b/3 Open-label Trial of VTS-270 (2-hydroxypropyl-β-cyclodextrin) in Subjects With Neurologic Manifestations of Niemann-Pick Type C1 Disease Previously Treated Under Protocol VTS301
Estimated Study Start Date : March 30, 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: VTS-270
Eligible participants who transition into this study will receive treatment with VTS-270 at the last dose level administered in Study VTS301, administered IT via LP infusion every 2 weeks, for up to a total duration of 3 years or until the investigator considers VTS-270 to be no longer beneficial to the subject, VTS-270 receives marketing authorization, or the VTS-270 development program is discontinued.
Drug: VTS-270
Lumber intrathecal infusion of VTS-270
Other Names:
  • 2-hydroxypropyl-β-cyclodextrin
  • Cyclodextrin




Primary Outcome Measures :
  1. 1. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: up to Week 180 ]
    An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were AEs excluding non-serious AEs.

  2. Change from Baseline in Body Weight [ Time Frame: Baseline and Weeks 26, 52, 78, 104, 130, 156, 182 and at end of study (3 years) ]
  3. Change from Baseline in Clinically Significant Laboratory Test Abnormalities [ Time Frame: Baseline and Weeks 26, 52, 78, 104, 130, 156, 182 and at end of study (3 years) ]
    Laboratory tests will include Serum chemistry, Hematology assays and Urinalysis.

  4. Change From Baseline in Clinician Global Impression of Change (CGIC) Using Likert Score [ Time Frame: Weeks 26, 52, 78, 104, 130, 156, 182 and at end of study (3 years) ]
    The clinician-CGIC, evaluated using a 7-point Likert scale ranging from 1 = marked improvement since baseline to 7 = marked worsening since baseline, will be assessed at the specified time points.

  5. Blinded Clinician-CGIC at each assessment compared to Baseline [ Time Frame: Baseline and Weeks 26, 52, 78, 104, 130, 156, 182 and at end of study (3 years) ]
    The clinician-CGIC is to be conducted by a clinician, trained in performing neurological examinations. This rater will meet with the participant/parent or legal guardian (or caregiver) at the first visit (Baseline Visit) or first visit where this is scheduled if not done at the Baseline Visit, and establish a clinical assessment of the participant based on input from both subject and caregiver according to a standardized review of clinical status and functionality. This assessment, completed at the Baseline Visit prior to administration of the participant's first dose of study drug, is to allow the rater to establish an overall clinical baseline assessment of the participant's status and functionality. The clinician-CGIC, evaluated using a 7-point Likert scale ranging from 1 = marked improvement since baseline to 7 = marked worsening since baseline, will be assessed.

  6. Change from Baseline in NPC-SS total score (hearing and auditory brainstem response [ABR] removed) [ Time Frame: Baseline and Weeks 26, 52, 78, 104, 130, 156, 182 and at end of study (3 years) ]
    The ABR will be used to assess functional integrity of the auditory nerve and auditory brainstem pathways in those participants in whom pure tone audiometry cannot be conducted. A hearing threshold will not be obtained, but the waveform morphology and latencies will be evaluated. NPC-SS scale is based on 9 domains- Eye Movement, Ambulation, Speech, Swallow, Fine Motor Skills, Cognition, Hearing (sensineural), Memory and Seizures. A Likert-like scale will be used to assign nine major domain scores of 0 to 5 (better to worst).

  7. Proportion of responders (defined as no change or improvement on NPC-SS total score with hearing domain and ABR modifiers removed) [ Time Frame: Weeks 26, 52, 78, 104, 130, 156, 182 and at end of study (3 years) ]
    NPC-SS scale is based on 9 domains- Eye Movement, Ambulation, Speech, Swallow, Fine Motor Skills, Cognition, Hearing (sensineural), Memory and Seizures. A Likert-like scale will be used to assign nine major domain scores of 0 to 5 (better to worst).

  8. Change from Baseline in the caregiver ratings of quality of life using the European Quality of Life-5 Dimensions Quality of Life Rating (EQ-5D-3L) questionnaire at each assessment [ Time Frame: Baseline and Weeks 26, 52, 78, 104, 130, 156, 182 and at end of study (3 years) ]
    The EQ-5D-3L assessment is a self-reported, simple, descriptive system measuring 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

  9. Change from Baseline to each assessment in each of the 9 clinical domains of the NPC-SS [ Time Frame: Baseline and Weeks 26, 52, 78, 104, 130, 156, 182 and at end of study (3 years) ]
    Data for the NPC clinical severity scale rating will be collected at each study center by a trained rater. The trained rater will collect the data using a directed source document to permit consistent collection of NPC-specific domain information. This information will be provided to a centralized independent rater who will analyze all NPC information for all participants across all study centers. NPC-SS scale is based on 9 domains- Eye Movement, Ambulation, Speech, Swallow, Fine Motor Skills, Cognition, Hearing (sensineural), Memory and Seizures. A Likert-like scale will be used to assign nine major domain scores of 0 to 5 (better to worst).

  10. Change from Baseline to each assessment in the total NPC-SS with hearing domain and ABR modifier included [ Time Frame: Baseline and Weeks 26, 52, 78, 104, 130, 156, 182 and at end of study (3 years) ]
    Data for the NPC clinical severity scale rating will be collected at each study center by a trained rater. The trained rater will collect the data using a directed source document to permit consistent collection of NPC-specific domain information. This information will be provided to a centralized independent rater who will analyze all NPC information for all participants across all study centers. NPC-SS scale is based on 9 domains- Eye Movement, Ambulation, Speech, Swallow, Fine Motor Skills, Cognition, Hearing (sensineural), Memory and Seizures. A Likert-like scale will be used to assign nine major domain scores of 0 to 5 (better to worst).

  11. Time to a 1-point increase (worsening) in the NPC-SS composite score [ Time Frame: Weeks 26, 52, 78, 104, 130, 156, 182 and at end of study (3 years) ]
    Data for the NPC clinical severity scale rating will be collected at each study center by a trained rater. The trained rater will collect the data using a directed source document to permit consistent collection of NPC-specific domain information. This information will be provided to a centralized independent rater who will analyze all NPC information for all participants across all study centers. NPC-SS scale is based on 9 domains- Eye Movement, Ambulation, Speech, Swallow, Fine Motor Skills, Cognition, Hearing (sensineural), Memory and Seizures. A Likert-like scale will be used to assign nine major domain scores of 0 to 5 (better to worst).

  12. Composite NPC-SS mean annualized rate of change (slope) from Baseline to each assessment [ Time Frame: Baseline and Weeks 26, 52, 78, 104, 130, 156, 182 and at end of study (3 years) ]
    Data for the NPC clinical severity scale rating will be collected at each study center by a trained rater. The trained rater will collect the data using a directed source document to permit consistent collection of NPC-specific domain information. This information will be provided to a centralized independent rater who will analyze all NPC information for all participants across all study centers. NPC-SS scale is based on 9 domains- Eye Movement, Ambulation, Speech, Swallow, Fine Motor Skills, Cognition, Hearing (sensineural), Memory and Seizures. A Likert-like scale will be used to assign nine major domain scores of 0 to 5 (better to worst).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   4 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

To be eligible to participate in the study, at the Baseline Visit (except as noted below):

  1. Subject completed Part B of Study VTS301 (defined as having completed Visit 27/Week 52 or completed at least through Visit 13/Week 24 and required rescue option) and is continuing in Part C of Study VTS301.
  2. Subject, in the opinion of the PI, should continue treatment with VTS-270.
  3. Females of childbearing potential (not surgically sterile) must use a medically acceptable method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study. Acceptable methods of contraception include barrier method with spermicide, intrauterine device, steroidal contraceptive in conjunction with a barrier method, abstinence, or same-sex partner.
  4. Subject or parent/guardian must provide written informed consent to participate in the study. In addition to parental consent, assent to participate must also be sought from minor children.

Key Exclusion Criteria:

A subject is ineligible for study participation if, at the Baseline Visit:

  1. Subjects discontinued from Study VTS301 for AEs or perceived lack of efficacy.
  2. Subject has an unresolved SAE for which treatment with VTS-270 has been halted.
  3. Female subjects who are pregnant or nursing.
  4. Subjects with suspected infection of the central nervous system or any systemic infection.
  5. Subjects with a spinal deformity that could impact the ability to perform a LP.
  6. Subjects with a skin infection in the lumbar region within 2 months of study entry.
  7. Any of the following laboratory abnormalities at the Baseline Visit:

    1. Neutropenia, defined as an absolute neutrophil count of less than 1.5 × 109/L.
    2. Thrombocytopenia (platelet count of less than 75 × 109/L).
    3. Activated partial thromboplastin time or prothrombin time prolonged by greater than 1.5 × the upper limit of normal (ULN) or known history of a bleeding disorder.
    4. Aspartate aminotransferase or alanine aminotransferase (ALT) greater than 4 × ULN.
    5. Anemia: hemoglobin greater than 2 standard deviations below normal for age and gender.
    6. Estimated glomerular filtration rate less than 60 mL/minute/1.73 m2 calculated using the modified Schwartz formula (Schwartz et al., 2009) for subjects aged 4 through 17 years old or using the Chronic Kidney Disease Epidemiology Collaboration equation formula for subjects aged 18 years or older.
  8. Evidence of obstructive hydrocephalus or normal pressure hydrocephalus.
  9. Recent use of anticoagulants (in past 2 weeks prior to first dose [Study Day 0]).
  10. Active pulmonary disease, oxygen requirement, or clinically significant history of decreased blood oxygen saturation, pulmonary therapy, or requiring active suction.
  11. Subjects who, in the opinion of the investigator, are unable to comply with the protocol or have medical conditions that would potentially increase the risk of participation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03879655


Contacts
Layout table for location contacts
Contact: Study Study Director 1-800-556-3314 clinicaltrials@mnk.com

Sponsors and Collaborators
Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company

Layout table for additonal information
Responsible Party: Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company
ClinicalTrials.gov Identifier: NCT03879655     History of Changes
Other Study ID Numbers: VTS-270-302
First Posted: March 19, 2019    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company:
Niemann-Pick
NPC

Additional relevant MeSH terms:
Layout table for MeSH terms
Pick Disease of the Brain
Niemann-Pick Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Aphasia, Primary Progressive
Frontotemporal Dementia
Neurologic Manifestations
Frontotemporal Lobar Degeneration
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Signs and Symptoms
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Histiocytosis, Non-Langerhans-Cell
Histiocytosis