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Niemann-Pick Disease, Type CPhase 2NCT03687476

Safety and Tolerability Study of VTS-270 in Pediatric Participants With Niemann-Pick Type C (NPC) Disease

A Phase 2 study testing VTS-270 in people with Niemann-Pick Disease, Type C, run by Vtesse, LLC, a Mallinckrodt Pharmaceuticals Company.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a Phase-2, multicenter, multiple dose, open-label, 2-part evaluation study which will primarily assess the safety and tolerability of VTS-270 (2-hydroxypropyl beta-cyclodextrin [HP-β-CD]) in pediatric participants with age <4 years. Read more about this study

Who is it for?
Ages Up to 4 years
Conditions the study is for
Niemann-Pick Disease, Type C
What is being tested?
VTS-270
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
May 2020to 30 Oct 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 4 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • The parent(s)/legal guardian(s) must be adequately informed and understand the nature and risks of the study. The participant's parent or legal guardian must provide a signature and date on the informed consent form (ICF).
  • Participants must have neurologial symptoms defined as, any area of developmental delay 1 SD below the mean (example, developmental quotient or standard score under 85 in any domain on the Mullen Scale Early Learning [MSEL]) or a significant developmental quotient /standard score drop on the MSEL.
  • Diagnosis of NPC determined by one of the following:
  • Two NPC1 or NPC2 mutations;
  • Positive filipin staining or oxysterol testing and at least one NPC1 or NPC2 mutation;
  • Vertical supranuclear gaze palsy in combination with either:
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  • One NPC1/NPC2 mutation, or
  • Positive filipin staining or oxysterol levels consistent with NPC1 or NPC2 disease.
  • If taking miglustat (Zavesca), participant(s) must have been on a stable dose for 6 weeks prior to the Screening Visit and willing to remain on a stable dose for the duration of participation in this study. If not taking migulstat, the participant must have been off treatment for a minimum of 6 weeks prior to the Baseline Visit.
  • If a participant has a history of seizures, the condition must be adequately controlled (the pattern of seizure activity must be stable) and the participant must be on a stable dose and regimen of antiepileptic medication(s) 4 weeks prior to the Screening Visit.
  • Prior exposure to VTS-270 is permitted.
  • The participant's parent(s)/legal guardian(s) are able to communicate effectively with study personnel.
  • Parent(s)/legal guardian(s) are able and willing to follow all protocol requirements and study restrictions.
  • Parent(s)/legal guardian(s) are able and willing to return participants for all study visits.

Who cannot join

  • Is from a vulnerable population, as defined by the US CFR Title 45, Part 46, Section 46.111(b) and other local and national regulations, including but not limited to, employees (temporary, part-time, full time, etc) or a family member of the research staff conducting the study, or of the sponsor, or of the contract research organization, or of the institutional review board (IRB)/independent ethics committee (IEC).
  • Has a history of sensitivity or allergy to any product containing HP-β-CD.
  • A history of hypersensitivity reactions or allergy to the anesthetic and/or sedative agents to be used for the lumbar puncture procedure.
  • Taken an anticoagulant in the 2 weeks prior to the Baseline Visit or plan to use anticoagulants during the study.
  • Change in antiepileptic treatment between the Screening Visit and the Baseline Visit.
  • Received treatment for any investigational product (exclusive of VTS-270) within 4 weeks of the Baseline Visit or at least 5 half-lives, whichever criteria is longest.
Show all 19Show fewer
  • A suspected infection of the central nervous system or any systemic infection.
  • A spinal deformity that is likely to impact the ability to perform repeated LPs.
  • Evidence of obstructive hydrocephalus or normal pressure hydrocephalus.
  • Undergoing intravenous treatment with VTS-270. Note: prior or current treatment with IT VTS-270 is not exclusionary.
  • A known bleeding disorder.
  • Has any of the following laboratory abnormalities ( greater than 1.5 times the upper limit of normal) at the Screening Visit:
  • Neutropenia
  • Thrombocytopenia
  • Activated partial thromboplastin time
  • Prothrombin time prolongation.
  • Has any other clinically significant disease, disorder or laboratory abnormality, which, in the opinion of the investigator, might put the participant at risk due to participation in the study, or may influence the results of the study or the participant's ability to complete the study.
  • Is participating in or plans to participate in any other interventional research study from the time of screening and throughout this study.
  • Also excluded are participant, who in the opinion of the investigator, are unable to comply with the protocol or who have a medical condition (eg, cardiovascular, respiratory, hematologic, neurologic, psychiatric, renal) that would potentially increase the risk of study participation.

About this study

Official title: An Open-label, Multicenter Safety and Tolerability Study of VTS-270 (2-hydroxypropyl-β-cyclodextrin) in Pediatric Subjects Aged < 4 Years With Neurologic Manifestations of Niemann-Pick Type C (NPC) Disease

This is a Phase-2, multicenter, multiple dose, open-label, 2-part evaluation study which will primarily assess the safety and tolerability of VTS-270 (2-hydroxypropyl beta-cyclodextrin [HP-β-CD]) in pediatric participants with age <4 years.

Read the detailed description

In Part A of the study, participants after confirmation of the diagnosis of NPC will receive VTS-270 for 20 weeks during the active treatment period. Further, based on investigator's discretion participants would either end treatment with a follow-up visit 28 days (+/- 7) days after last treatment, or will enter to Part-B to benefit from open-label treatment.

Being tested
VTS-270
Medical subject headings
Niemann-Pick Disease, Type C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VTS-270Drug

    VTS-270 200 mg/mL administered as described in the arm group description.

Study groups in NCT03687476
Study groupRoleWhat they receive
VTS-270 (Part A)ExperimentalVTS-270 200 milligram per milliliter (mg/mL) will be administered intrathecally by lumbar puncture every 2 weeks followed by dose escalation of 100 mg/mL increments up to a maximum tolerable dose of 900 mg/mL. The highest tolerable dose is considered as clinically relevant dose which will be administered throughout the remaining duration of the 20-week treatment period of Part A.
Receives: Drug: VTS-270
VTS-270 (Part B)ExperimentalVTS-270 200 mg/mL will be administered intrathecally by lumbar puncture every 2 weeks in Part B followed by a re-challenge to dose escalation of 100 mg/mL increments up to a maximum tolerable dose of 900 mg/mL. In case of intolerance, the dose should be returned to previously tolerable dose and should be continued throughout the duration of Part B (end of study).
Receives: Drug: VTS-270

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs): Part A

    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. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. SAEs were AEs excluding non-serious AEs.

    Measured: Baseline up to Week 20 (End of Part A)

  2. Number of Participants With Clinically Significant Vital Signs: Part A

    Clinically significant vital sign is defined as an abnormal vital sign result that results in a treatment-emergent AEs. Abnormal clinically significant vital signs included absolute systolic blood pressure (BP) values less than (<) 90 millimeter of mercury (mmHg), maximum increase or decrease of greater than or equal to (>=) 30 mmHg from baseline for systolic BP; absolute diastolic BP <50 mmHg with maximum increase or decrease of >=20 mmHg from baseline and absolute heart rate values <40 beats per minute (bpm), >120 bpm for supine or sitting measurement, >140 bpm for standing measurement, temperature <32 or >40 degree centigrade, respiratory rate of <10 or >50 breaths/minute.

    Measured: Baseline up to Week 20 (End of Part A)

  3. Number of Participants With Clinically Significant Change from Baseline in Body Weight: Part A

    Any change from baseline in body weight is considered by the investigator to be clinically significant and will be recorded as treatment-emergent AE.

    Measured: Baseline up to Week 20 (End of Part A)

  4. Number of Participants With Clinically Significant Change from Baseline in Body Height: Part A

    Any change from baseline in body height is considered by the investigator to be clinically significant and will be recorded as treatment-emergent AE.

    Measured: Baseline up to Week 20 (End of Part A)

  5. Number of Participants With Clinically Significant Laboratory Test Abnormalities: Part A

    Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit and red blood cells (< 0.8*lower limit of normal[LLN]); leucocytes (<0.6/>1.5*upper limit of normal [ULN]); platelets (<0.5*LLN/>1.75*ULN); neutrophils, lymphocytes (<0.8*LLN/>1.2*ULN); eosinophils, basophils, monocytes (>1.2*ULN); total bilirubin (>1.5*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (>3*ULN), total protein, albumin (<0.8*LLN/>1.2*ULN); creatinine, urea (>1.3*ULN); glucose (<0.6*LLN/>1.5*ULN); uric acid (>1.2*ULN); sodium, potassium, chloride, calcium, bicarbonate (<0.9*LLN/>1.1*ULN); urine red blood cells (RBCs), urine white blood cells (WBCs), urine epithelial cells (>=6 high-powered field), urine bacteria >20 high-powered field; qualitative urine glucose, ketones, protein values >=1 in urine dipstick test. Total number of participants with any laboratory abnormalities was reported.

    Measured: Baseline up to Week 20 (End of Part A)

Secondary outcomes (10)

  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs): Part B

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was 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. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. SAEs were AEs excluding non-serious AEs.

    Measured: Week 22 up to 3 years (End of Study or Part B)

  2. Number of Participants With Clinically Significant Vital Signs: Part B

    Clinically significant vital sign is defined as an abnormal vital sign result that results in a treatment-emergent AEs. Abnormal clinically significant vital signs included absolute systolic blood pressure (BP) values less than (<) 90 millimeter of mercury (mmHg), maximum increase or decrease of greater than or equal to (>=) 30 mmHg from baseline for systolic BP; absolute diastolic BP <50 mmHg with maximum increase or decrease of >=20 mmHg from baseline and absolute heart rate values <40 beats per minute (bpm), >120 bpm for supine or sitting measurement, >140 bpm for standing measurement, temperature <32 or >40 degree centigrade, respiratory rate of <10 or >50 breaths/minute.

    Measured: Week 22 up to 3 years (End of Study or Part B)

  3. Number of Participants With Clinically Significant Change from Baseline in Body Weight: Part B

    Any change from baseline in body weight is considered by the investigator to be clinically significant and will be recorded as treatment-emergent AE.

    Measured: Week 22 up to 3 years (End of Study or Part B)

  4. Number of Participants With Clinically Significant Change from Baseline in Body Height: Part B

    Any change from baseline in body height is considered by the investigator to be clinically significant and will be recorded as treatment-emergent AE.

    Measured: Week 22 up to 3 years (End of Study or Part B)

  5. Number of Participants With Clinically Significant Laboratory Test Abnormalities: Part B

    Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit and red blood cells (< 0.8*lower limit of normal[LLN]); leucocytes (<0.6/>1.5*upper limit of normal [ULN]); platelets (<0.5*LLN/>1.75*ULN); neutrophils, lymphocytes (<0.8*LLN/>1.2*ULN); eosinophils, basophils, monocytes (>1.2*ULN); total bilirubin (>1.5*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (>3*ULN), total protein, albumin (<0.8*LLN/>1.2*ULN); creatinine, urea (>1.3*ULN); glucose (<0.6*LLN/>1.5*ULN); uric acid (>1.2*ULN); sodium, potassium, chloride, calcium, bicarbonate (<0.9*LLN/>1.1*ULN); urine red blood cells (RBCs), urine white blood cells (WBCs), urine epithelial cells (>=6 high-powered field), urine bacteria >20 high-powered field; qualitative urine glucose, ketones, protein values >=1 in urine dipstick test. Total number of participants with any laboratory abnormalities was reported.

    Measured: Week 22 up to 3 years (End of Study or Part B)

  6. Change From Baseline in Audiological Examinations at Week 6, 12, 20, 44, and every 24 Week Thereafter Until End of Treatment (EOT: 3 Years)

    Standard developmentally appropriate audiological examinations suited to the individual participants will be used to assess auditory system function (physical tests: tympanometry and otoacoustic emissions) and hearing sensitivity (behavioral test: word recognition and pure-tone and speech thresholds).

    Measured: Baseline, Week 6, 12, 20, 44, every 24 Week thereafter until EOT (3 years)

  7. Change From Baseline in Cognitive and Motor Development Assessed Using Mullen Scale of Early Learning (MSEL) at Week 6, 12, 20, 44, and every 24 Week Thereafter Until End of Treatment (EOT: 3 Years)

    The MSEL is a standardized developmental test for children consisting of five subscales: fine motor, visual reception, expressive language, receptive language and an optional fifth gross motor scale (scale includes standing, walking and running) that only measures skills to 36 months. The raw score is reported for each subscale domain. The potential score ranges are as follows: Visual Reception: 33 items, score range=0-50, Fine Motor: 30 items, score range= 0-49, Receptive Language: 33 items, score range= 0-48, Expressive Language: 28 items, score range= 0-50. A higher raw score indicates more advanced abilities in that section.

    Measured: Baseline, Week 6, 12, 20, 44, every 24 Week thereafter until EOT (3 years)

  8. Change From Baseline in Auditory Brainstem Response (ABR) Assessed Using Standard Clinical Pediatric Score at Week 6, 12, 20, 44, and every 24 Week Thereafter Until End of Treatment (EOT: 3 Years)

    The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were based on standard clinical pediatric score criteria: mild hearing loss: 21-40 decibels hearing level (dBHL), moderate hearing loss: 41-70 dBHL, severe hearing loss: 71-90 dBHL, profound hearing loss: 91dBHL.

    Measured: Baseline, Week 6, 12, 20, 44, every 24 Week thereafter until EOT (3 years)

  9. Change From Baseline in Clinician Global Impression of Change (CGIC) Using Likert Score at Week 6, 12, 20, 44, and every 24 Week Thereafter Until End of Treatment (EOT: 3 Years)

    The Clinician-CGIC is conducted by a clinician who is trained in performing neurological examinations. CGIC is measured using 7-point Likert scale ranging from 1 = "very much improved" to 7 = "very much worse". If the rater notes an improvement or worsening on the scale, the rater should indicate the major factor for the reported changes in score.

    Measured: Baseline, Week 6, 12, 20, 44, every 24 Week thereafter until EOT (3 years)

  10. Change From Baseline in Caregiver Global Impression of Change (CGIC) Using Likert Score at Week 6, 12, 20, 44, and every 24 Week Thereafter Until End of Treatment (EOT: 3 Years)

    The caregiver-CGIC is to be completed by the responsible parent or legal guardian. CGIC is measured using 7-point Likert scale ranging from 1 = "very much improved" to 7 = "very much worse". If the caregiver notes an improvement or worsening on the scale, the caregiver should indicate the major reason for the reported changes in score.

    Measured: Baseline, Week 6, 12, 20, 44, every 24 Week thereafter until EOT (3 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2018
  2. Study startMay 2020 (estimated)
  3. Primary completion30 Oct 2022 (estimated)
  4. Study completion30 Oct 2022 (estimated)

Why it stopped: Business decision to Cancel

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03687476
Sponsor's protocol ID
VTS270-303
Status last verified
Jul 2020
First submitted
6 Aug 2018
Last updated
22 Jul 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing VTS-270 in people with Niemann-Pick Disease, Type C, run by Vtesse, LLC, a Mallinckrodt Pharmaceuticals Company.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 22 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs): Part A (time frame: Baseline up to Week 20 (End of Part A)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03687476.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2020.

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