Clinical Trial: Arimoclomol Prospective Study in Patients Diagnosed With NiemannPick Disease Type C

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Arimoclomol Prospective Doubleblind, Randomised, Placebo-controlled Study in Patients Diagnosed With NiemannPick Disease Type C

Brief Summary:

A prospective, randomised, double-blind, placebo controlled therapeutic study in patients with confirmed diagnosis of NiemannPick disease type C (NPC).

The purpose of this study is to assess the efficacy and safety of arimoclomol (compared to placebo) when it is administered as an add-on therapy to the patient's current prescribed best standard of care; patient's standard of care may, or may not, include miglustat.


Detailed Summary:

A prospective, randomised, double-blind, placebo controlled therapeutic study in patients with confirmed diagnosis of NiemannPick disease type C (NPC).

Patients must either 1) have completed Visit 2 (end of study [EOS]) of the CTORZYNPC001 study or 2) meet the eligibility criteria of this study including a requirement of stable treatment with miglustat for 6 months (if on miglustat therapy) prior to enrolment into the study.

Aim:

The purpose of this study is to assess the efficacy and safety of arimoclomol (compared to placebo) when it is administered as an add-on therapy to the patient's current prescribed best standard of care; patient's standard of care may, or may not, include miglustat.

Randomisation:

Patients will be randomised to receive placebo or arimoclomol (with an allocation ratio of 1:2).

Pharmacokinetic evaluation(age below 12):

To confirm the selected dose, patients less than 12 years of age will undergo an arimoclomol single-dose pharmacokinetic (PK) evaluation before randomisation and the start of continuous (multiple dosing) treatment.

Early Escape Clause:

In patients whose disease progression is too severe and/or too fast, the "early escape clause" will allow the Investigator to apply the escape route which implies that the patient can be treated with arimoclomol (as per blinded phase study schedule) and be followed up on an annual basis until arimoclomol has received EU MA or until the analysis of data from the controlled, 12 month blinded phase stud
Sponsor: Orphazyme

Current Primary Outcome: Change in NPC disease severity score [ Time Frame: baseline (Visit 1) to 12 months ]

Change in the NPC disease severity based on the NPCCSS scores (Yanjanin et al., 2010).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in the Niemann Pick type C Clinical Database (NPC-cdb) score [ Time Frame: baseline (Visit 1) to 6 months, 12, 18, 24 and 36 months ]
    Change in the Niemann Pick type C Clinical Database (NPC-cdb) score (modified "Stampfer Score" [Stampfer et al., 2013]).
  • Change in NPCCSS score [ Time Frame: baseline (Visit 1) to 6 months, 18, 24 and 36 months ]
    Change in the NPC disease severity based on the NPCCSS scores (Yanjanin et al., 2010).
  • Change in NPCCSS score (individual domains) [ Time Frame: baseline (Visit 1) to 6 months, 12, 18, 24 and 36 months ]
    Change in the individual domains of the NPC disease severity based on the NPCCSS scores (Yanjanin et al., 2010).
  • Change in Quality of Life (EQ5DY) [ Time Frame: baseline (Visit 1) to 6 and 12 , 18, 24 and 36 months ]
    Change in Quality of Life (EQ5DY)
  • Change in the SARA score [ Time Frame: baseline (Visit 1) to 6 and 12 , 18, 24 and 36 months ]
    Change in the SARA score
  • Change in the 9HPT (9 Hole Peg Test) [ Time Frame: baseline (Visit 1) to 6 and 12 , 18, 24 and 36 months ]
    Change in the 9HPT
  • Adverse events (AEs); [ Time Frame: Baseline (visit 1) - 36 months ]
    Collection of safety data: Adverse events (AEs); Haematology; Clinical chemistry; Physical examination; Vital signs; Electrocardiogram (ECG).


Original Secondary Outcome:

  • Change in the Niemann Pick type C Clinical Database (NPC-cdb) score [ Time Frame: baseline (Visit 1) to 6 and 12 months ]
    Change in the Niemann Pick type C Clinical Database (NPC-cdb) score (modified "Stampfer Score" [Stampfer et al., 2013]).
  • Change in NPCCSS score [ Time Frame: baseline (Visit 1) to 6 months, 24 and 36 months ]
    Change in the NPC disease severity based on the NPCCSS scores (Yanjanin et al., 2010).
  • Change in NPCCSS score (individual domains) [ Time Frame: baseline (Visit 1) to 6 months, 12 months, 24 and 36 months ]
    Change in the individual domains of the NPC disease severity based on the NPCCSS scores (Yanjanin et al., 2010).
  • Change in Quality of Life (EQ5DY) [ Time Frame: baseline (Visit 1) to 6 and 12 , 24 and 36 months ]
    Change in Quality of Life (EQ5DY)
  • Change in the NPC disease progression rate [ Time Frame: baseline(visit 1) to 6 and 12 months ]
    Change in the NPC disease progression rate based on the NPCCSS scores
  • Changes in the size of the liver and spleen (assessed by ultrasound). [ Time Frame: baseline(visit 1) to 6 and 12 months ]
    Changes in the size of the liver and spleen (assessed by ultrasound).
  • Change in biomarkers [ Time Frame: baseline(visit 1) to 6 and 12 months, 24 and 36 months ]
    Analysis for biomarkers in biological material: NPC1 active protein; NPC1 protein function (cholesteryl esterification); Oxysterols; Un-esterified cholesterol and HSP70.
  • Adverse events (AEs); [ Time Frame: Baseline (visit 1) - 36 months ]
    Collection of safety data: Adverse events (AEs); Haematology; Clinical chemistry; Physical examination; Vital signs; Electrocardiogram (ECG).


Information By: Orphazyme

Dates:
Date Received: November 12, 2015
Date Started: June 2016
Date Completion: December 2017
Last Updated: May 17, 2017
Last Verified: May 2017