A Safety Study of NNZ-2566 in Patients With Rett Syndrome
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Rett Syndrome |
Drug: NNZ-2566 Drug: Placebo |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Phase IIa Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Escalation Study of NNZ-2566 in Rett Syndrome |
- Adverse events [ Time Frame: Through to Day 14 ] [ Designated as safety issue: Yes ]Incidence of adverse events from randomization through to end of study drug administration (Day 14).
- Serious adverse events [ Time Frame: Through to Day 28. ] [ Designated as safety issue: Yes ]Incidence of serious adverse events from randomization through to final follow-up assessment (Day 28).
- Change in EEG activity [ Time Frame: From baseline through to Day 28 ] [ Designated as safety issue: No ]
Absolute change in the number of spikes in the EEG per hour during the awake state will be calculated within subjects between baseline (pre-treatment), during treatment (Days 1 thru 4, and Day 14) and after treatment (Days 17 and 28).
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 within subjects between baseline (pre-treatment), during treatment (Days 1 thru 4, and Day 14) and after treatment (Days 17 and 28).
Changes in the frequency of the characteristic repetitive stereotypic hand movements during wakefulness will be calculated within subjects between baseline (pre-treatment), during treatment (Days 1 thru 3, and Day 14) and after treatment (Days 17 and 28).
- Behavior [ Time Frame: Baseline and Day 14 ] [ Designated as safety issue: No ]
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).
In addition the following assessments will be undertaken at the timepoints specified: CGI-S (screening, Days 1, and 28), CGI-I (Days 5, 14, 17, 28), MBA (Day 28), CSS (screening, Day 28).
- Physiological changes [ Time Frame: Baseline through to Day 28 ] [ Designated as safety issue: No ]Changes in autonomic function, i.e. respiratory rhythm, hyperventilation, apneas, oxygen desaturation, heart rate variation and cardiorespiratory coupling will be calculated between baseline (pre-treatment), during treatment (Days 1 thru 3, and Day 14) and after treatment (Days 17 and 28).
- Global and Functional outcome Measures [ Time Frame: Baseline through to Day 28 ] [ Designated as safety issue: No ]
- 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 and during treatment (Day 5 CGI-I only), post treatment (Days 14, 17(CGI-I only) and 28).
- Changes in caregiver assessment of the top three causes for concern as captured via a Visual Analogue Scale (VAS) will be calculated within subjects between baseline (pre-treatment), during treatment (Day 14) and after treatment (Days 17 and 28)
- Changes in the Aberrant Behavior Checklist (ABC) and Vineland Adaptive Behavior Scales (VABS) will be calculated within subjects between baseline (pre-treatment), and during treatment (Day 14).
- Pharmacokinetics [ Time Frame: Baseline through to Day 28 ] [ Designated as safety issue: No ]The following pharmacokinetic measures will be calculated from NNZ-2566 concentrations in whole blood: Cmax (peak), Cmin (trough), CAV at steady state. These parameters will be compared between dose groups for both mutation type groups.
| Estimated Enrollment: | 60 |
| Study Start Date: | March 2013 |
| Estimated Study Completion Date: | May 2014 |
| Estimated Primary Completion Date: | March 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: NNZ-2566
Glycyl-L-2-Methylpropyl-L-Glutamic Acid
|
Drug: NNZ-2566
Glycyl-L-2-Methylpropyl-L-Glutamic Acid (NNZ-2566) supplied as a lyophilized powder (2g in 50mL vials) for reconstitution with strawberry flavored solution in Water for Injection.
Other Name: NNZ-2566
|
|
Placebo Comparator: Placebo (strawberry flavored solution)
Strawberry flavored solution and Water for Injection
|
Drug: Placebo
Strawberry flavored solution and Water for Injection
Other Name: Strawberry flavored solution 1:1 in Water for Injection
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 16 Years to 40 Years |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Diagnosis of Rett Syndrome with proven mutation of the MeCP2 gene
- Age 16 to 40 years
- Severity rating of between 10 and 36 (Rett Syndrome Natural History/Clinical Severity Scale)
- Concomitant medications must be stable for >4 weeks prior to enrollment. The following concomitant medications are permitted: anticonvulsants which do not have liver inducing effects; beta-blockers; medications for the treatment of gastroesophageal reflux disease (GERD); medications for the treatment of anxiety, of depression and of psychosis.
- Ability to swallow study medication provided as a liquid solution, or via gastrostomy tube
Exclusion Criteria:
- No detectable abnormality of the EEG during screening period
- Actively undergoing regression
- QTcF exclusions (any of the following): baseline/screening QT/QTcF interval of 450 msec; history of risk factors for torsade de pointes (e.g. heart failure, hypokalemia (serum potassium at screening < 3.0 mmol/L) or family history of long QT syndrome; QT/QTcF prolongation previously or currently controlled with medication
- Current treatment with insulin
- Hgb A1C values outside the normal reference range at baseline or screening
- Current or past treatment with IGF-1
- Current or past treatment with growth hormone
- Current treatment with N-methyl-D-aspartate (NMDA) antagonists
- Current or planned use of non-medication based interventional therapy during the period of the study (defined as 4 week screening period followed by 2 week dosing and 2 week follow-up period)
- Current clinically significant cardiovascular, renal, hepatic or respiratory disease
- Gastrointestinal disease which may interfere with the absorption, distribution, metabolism or excretion of the the study medication
- History of, or current cerebrovascular disease or brain trauma
- History of, or current significant endocrine disorder e.g. hypo or hyperthyroidism or diabetes mellitus
- History of, or current malignancy
- Clinically significant abnormalities in safety laboratory tests, vital signs or ECG, as measured at screening or baseline
- Significant hearing and/or visual impairment that may affect ability to complete the test procedures
- Enrollment in another clinical trial within the previous 30 days
- Prior enrollment in this clinical trial
Contacts and Locations| Contact: Joseph Horrigan, M.D. | jhorrigan@neurenpharma.com | |
| Contact: Margaret Scott | mscott@neurenpharma.com |
| United States, Texas | |
| Baylor School of Medicine | Recruiting |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: | Daniel G Glaze, M.D. | Baylor College of Medicine |
| Principal Investigator: | Jeffrey L Neul, M.D., Ph.D. | Baylor College of Medicine |
More Information
No publications provided
| Responsible Party: | Neuren Pharmaceuticals Limited |
| ClinicalTrials.gov Identifier: | NCT01703533 History of Changes |
| Other Study ID Numbers: | Neu-2566-RETT-001 |
| Study First Received: | October 4, 2012 |
| Last Updated: | March 3, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Neuren Pharmaceuticals Limited:
|
Autism Rett's Syndrome Rett Disorder Rett's Disorder Ataxia |
Additional relevant MeSH terms:
|
Rett Syndrome Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Nervous System Diseases Mental Retardation, X-Linked |
Mental Retardation Neurobehavioral Manifestations Neurologic Manifestations Genetic Diseases, X-Linked Genetic Diseases, Inborn |
ClinicalTrials.gov processed this record on May 16, 2013