Clinical Trial: A Safety Study of NNZ-2566 in Patients With Rett Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Escalation Study of NNZ-2566 in Rett Syndrome

Brief Summary: The purpose of this study is to determine whether NNZ-2566 is safe and well tolerated in the treatment of Rett Syndrome in adolescent and adult females.

Detailed Summary:

Rett Syndrome is a developmental disorder primarily if not exclusively affecting females. The disorder is characterized by apparent normal development in early infancy (6-18 months), followed by a period of regression with onset of systemic and neurological signs. The CNS symptoms of Rett Syndrome include learning disability, autism and epilepsy and these can be severe and highly debilitating. Affected individuals also show signs of autonomic dysfunction, reflected in cardiovascular and respiratory abnormalities. There is no currently effective treatment for Rett Syndrome.

This study will investigate the safety and tolerability of treatment with oral administration of NNZ-2566 at 35 mg/kg or 70 mg/kg BID in adolescent or adult females with Rett Syndrome. The study also will also investigate measures of efficacy during treatment.


Sponsor: Neuren Pharmaceuticals Limited

Current Primary Outcome: Adverse events [ Time Frame: Through to Day 40 ]

Incidence of adverse events (AE), including Serious adverse events (SAE), will be evaluated between the two NNZ-2566 doses and placebo. SAEs will be examined from randomization through to Day 40. AEs will be examined from dosing through to Day 40.


Original Primary Outcome:

  • Adverse events [ Time Frame: Through to Day 33 ]
    Incidence of adverse events and serious adverse events
  • Physiological changes [ Time Frame: Through to Day 33 ]
    Changes from baseline for selected serum chemistry parameters and changes in cardiac function as measured by electrocardiogram (ECG).


Current Secondary Outcome:

  • Change in EEG activity [ Time Frame: Baseline through to Day 40 ]

    Absolute change in the number of spikes in the EEG per hour during the awake state will be calculated for each subject between baseline (pre-treatment), during treatment (Days 1 thru 4, 14 and 26) and after treatment (Day 40).

    Absolute change in the power of frequency bands in the EEG over an hour in the awake state as determined by the Fast Fourier method will be calculated for each subject between baseline (pre-treatment), during treatment (Days 1 thru 4, 14 and 26) and after treatment (Day 40).

    Changes in the frequency of the characteristic repetitive stereotypic hand movements during wakefulness will be calculated for each subject between baseline (pre-treatment), during treatment (Days 1 thru 4, 14 and 26) and after treatment (Day 40).

  • Behavior [ Time Frame: Baseline through to Day 40 ]

    The following measures will be assessed at baseline and Day 26 and the changes compared between active and placebo groups:

    Symptom severity according to the Rett Syndrome Natural History Motor Behavior Assessment (MBA), Clinical Severity Scale (CSS), Aberrant Behavior Checklist (ABC), Vineland Adaptive Behavior Scale (VABS), and Clinical Global Impression of Severity (CGI-S).

    The following assessments will be undertaken at the additional time points specified: CGI-S (screening, baseline, Days 5, 14, 26, and 40), CGI-I (Days 5, 14, 26, and 40), MBA (Baseline, Days 26 and 40), CSS (screening, baseline, Days 26, and 40).

  • Physiological changes [ Time Frame: Baseline through to Day 40 ]
    Changes in autonomic function, i.e. respiratory rhythm, hyperventilation, apneas, oxygen desaturation, and heart rate variation will be calculated between baseline (pre-treatment), during treatment (Days 1 thru 4, 14 and 26) and after treatment (Day 40).
  • Global and Functional outcome Measures [ Time Frame: Baseline through to Day 40 ]

    Global outcome as measured by the change in scores on the Rett Syndrome Clinical Severity Score (CSS), The Rett Syndrome Motor-Behavior Assessment Scale (MBA), and the Clinical Global Impression - Severity and Improvement scales (CGI-S and -I) from baseline, during treatment, and post treatment.

    Changes in caregiver assessment of the top three causes for concern as assessed via a Visual Analogue Scale (VAS) will be evaluated for each subject between baseline (pre-treatment), during treatment (Day 26) and after treatment (Day 40).

    Changes in the Aberrant Behavior Checklist (ABC) and Vineland Adaptive Behavior Scales (VABS) will be calculated for each subject between baseline (pre-treatment), and during treatment (Day 26).



Original Secondary Outcome:

  • EEG and video monitoring [ Time Frame: Baseline, daily during first five days of dosing, Days 11, 23 and 33 ]
    EEG monitoring for seizure activity
  • Behavior [ Time Frame: Baseline and Day 23 ]
    Symptom severity according to various behavior and clinical severity assessment scales.
  • Physiological changes [ Time Frame: Baseline and Days 2, 4, 11, 23 and 33. ]
    Blood gas levels (baseline, Days 23 and 33), fundoscopy and tonsil size.


Information By: Neuren Pharmaceuticals Limited

Dates:
Date Received: October 4, 2012
Date Started: March 2013
Date Completion:
Last Updated: March 27, 2017
Last Verified: March 2017