A Safety Study of NNZ-2566 in Pediatric Rett Syndrome

Phase 2

Completed

• Conditions: Rett Syndrome
• Interventions: Drug: NNZ-2566; Drug: Placebo

• Registration Number: NCT02715115
• Lead Sponsor: Neuren Pharmaceuticals Limited

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 children and adolescents.

Detailed 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.

Study Timeline

• Study First Submitted: 2016-02-21
• Study Start: 2016-03
• Study First Submitted QC: 2016-03-16
• Study First Posted: 2016-03-22
• Primary Completion: 2017-01-05
• Study Completion: 2017-01-05
• Disposition First Submitted: 2018-01-22
• Disposition First Submitted QC: 2018-01-28
• Disposition First Posted: 2018-01-31
• Status Verified: 2020-08
• Last Update Submitted: 2020-08-06
• Last Update Posted: 2020-08-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 82

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NNZ-2566	NNZ-2566	Glycyl-L-2-Methylpropyl-L-Glutamic Acid
Placebo (strawberry flavored solution)	Placebo	Strawberry flavored solution and Water for Injection

Primary Outcome Measures

Name	Time	Method
Adverse events	Through study completion, an average of 11 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Clinical Global Impression of Improvement (CGI-I)	Through study completion, an average of 11 weeks
Motor Behaviour Assessment Scale (MBA)	Through study completion, an average of 11 weeks
Caregiver Top 3 Concerns via a Visual Analogue Scale (VAS)	Through study completion, an average of 11 weeks

Trial Locations

Locations (12)

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

Vanderbilt University; 🇺🇸 Nashville, Tennessee, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Greenwood Genetic Center; 🇺🇸 Greenwood, South Carolina, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

University of California, San Diego; 🇺🇸 San Diego, California, United States

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

Gillette Children's Specialty Healthcare; 🇺🇸 Saint Paul, Minnesota, United States

UCSF Benioff Children's Hospital Oakland; 🇺🇸 Oakland, California, United States

Children's Hosptial Colorado; 🇺🇸 Aurora, Colorado, United States