A Safety Study of NNZ-2566 in Pediatric Rett Syndrome

Rett Syndrome Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Dose-ranging Study of the Safety and Pharmacokinetics of Oral NNZ-2566 in Pediatric Rett Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02715115
• Other study ID #: Neu-2566-RETT-002
• Status: Completed
• Phase: Phase 2
• Start date: March 2016
• Est. completion date: January 5, 2017

Study information

• Verified date: August 2020
• Source: Neuren Pharmaceuticals Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether NNZ-2566 is safe and well tolerated in the treatment of Rett syndrome in children and adolescents.

Description:

Rett syndrome is a neurodevelopmental disorder primarily 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 symptomatology 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, tolerability and blood pharmacokinetics of treatment with oral administration of NNZ-2566 at 50 mg/kg, 100 mg/kg, 200 mg/kg BID, or placebo BID, in children and adolescent females with Rett syndrome. The study also will also investigate measures of efficacy and biomarkers during treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: January 5, 2017
• Est. primary completion date: January 5, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 5 Years to 15 Years

Eligibility

Inclusion Criteria:

• Diagnosis of classic/typical Rett syndrome with a documented mutation of the MeCP2 gene.

• Age 5 - 15 years.

• Weight at Screening and Baseline between 15.0 kg-100.0 kg (at least 15.0 kg and no greater than 100.0 kg).

• Each subject must be able to swallow the study medication provided as a liquid solution, or via gastrostomy tube.

Exclusion Criteria:

• Actively undergoing neurological regression

• Abnormal QT interval, prolongation or significant cardiovascular history.

• Current treatment with insulin.

• Anti-convulsants with liver enzyme inducing effects.

• Unstable seizure profile.

• Excluded concomitant medications.

• Current clinically significant (as determined by the investigator). cardiovascular, renal, hepatic, or respiratory disease.

• Gastrointestinal disease which may interfere with the absorption, distribution, metabolism or excretion of the study medication.

• History of, or current cerebrovascular disease or brain trauma.

• History of, or current clinically significant endocrine disorder, e.g. hypo- or hyperthyroidism, or diabetes mellitus.

• History of, or current, malignancy.

• Significant hearing and/or visual impairments that may affect ability to complete the test procedures.

• Allergy to strawberry.

Related Conditions & MeSH terms

• Rett Syndrome
• Syndrome

Intervention

Drug:
• NNZ-2566
Glycyl-L-2-Methylpropyl-L-Glutamic Acid (NNZ-2566) supplied as a lyophilized powder for reconstitution with strawberry flavored solution 0.5% v/v in Water for Injection.
• Placebo
Strawberry flavored solution and Water for Injection

Locations

Country	Name	City	State
United States	Children's Hosptial Colorado	Aurora	Colorado
United States	University of Alabama	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Greenwood Genetic Center	Greenwood	South Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Vanderbilt University	Nashville	Tennessee
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Gillette Children's Specialty Healthcare	Saint Paul	Minnesota
United States	University of California, San Diego	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
Neuren Pharmaceuticals Limited	rettsyndrome.org

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Incidence of adverse events (AEs), including serious adverse events (SAEs), will be compared across the three NNZ-2566 doses and placebo. SAEs and AEs will be examined throughout the study.	Through study completion, an average of 11 weeks
Secondary	Motor Behaviour Assessment Scale (MBA)		Through study completion, an average of 11 weeks
Secondary	Clinical Global Impression of Improvement (CGI-I)		Through study completion, an average of 11 weeks
Secondary	Caregiver Top 3 Concerns via a Visual Analogue Scale (VAS)		Through study completion, an average of 11 weeks