A Safety Study of NNZ-2566 in Pediatric Rett Syndrome

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

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.

Study Overview

• Status: Completed
• Conditions: Rett Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: NNZ-2566

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 Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital Oakland
    • San Diego, California, United States, 92093
      • University of California, San Diego
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hosptial Colorado
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Gillette Children's Specialty Healthcare
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Greenwood, South Carolina, United States, 29646
      • Greenwood Genetic Center
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Vanderbilt University
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 for reconstitution with strawberry flavored solution 0.5% v/v in Water for Injection.; Other Names: trofinetide
Placebo Comparator: Placebo (strawberry flavored solution); Strawberry flavored solution and Water for Injection	Drug: Placebo; Strawberry flavored solution and Water for Injection; Other Names: Strawberry flavoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
Motor Behaviour Assessment Scale (MBA)	Through study completion, an average of 11 weeks
Clinical Global Impression of Improvement (CGI-I)	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

Collaborators and Investigators

• Sponsor: Neuren Pharmaceuticals Limited
• Collaborators: rettsyndrome.org
• Investigators: Principal Investigator: Alan Percy, MD, University of Alabama at Birmingham; Principal Investigator: Timothy Feyma, MD, Gillette Children's Specialty Healthcare; Principal Investigator: Daniel Glaze, MD, Baylor College of Medicine; Principal Investigator: Peter Heydemann, MD, Rush University Medical Center; Principal Investigator: Jeff Neul, MD, University of California, San Diego; Principal Investigator: Tim Benke, MD, Children's Hospital Colorado; Principal Investigator: Mary Jones, MD, UCSF Benioff Children's Hospital Oakland; Principal Investigator: Mustafa Sahin, MD, Boston Children's Hospital; Principal Investigator: Sarika Peters, PhD, Vanderbilt University; Principal Investigator: Shannon Standridge, Children's Hospital Medical Center, Cincinnati; Principal Investigator: Eric Marsh, MD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): January 5, 2017
• Study Completion (Actual): January 5, 2017

Study Registration Dates

• First Submitted: February 21, 2016
• First Submitted That Met QC Criteria: March 16, 2016
• First Posted (Estimate): March 22, 2016

Study Record Updates

• Last Update Posted (Actual): August 14, 2020
• Last Update Submitted That Met QC Criteria: August 6, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Autism; Ataxia; Rett's syndrome; Rett disorder; Rett's disorder
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Syndrome; Rett Syndrome
• Other Study ID Numbers: Neu-2566-RETT-002