A Safety Study of NNZ-2566 in Pediatric Rett Syndrome

• ClinicalTrials.gov Identifier: NCT02715115
• Recruitment Status: Completed
• First Posted: March 22, 2016
• Last Update Posted: August 14, 2020
• Sponsor: Neuren Pharmaceuticals Limited
• Collaborator: rettsyndrome.org
• Information provided by (Responsible Party): Neuren Pharmaceuticals Limited

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Rett Syndrome	Drug: NNZ-2566; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 82 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Dose-ranging Study of the Safety and Pharmacokinetics of Oral NNZ-2566 in Pediatric Rett Syndrome
• Actual Study Start Date: March 2016
• Actual Primary Completion Date: January 5, 2017
• Actual Study Completion Date: January 5, 2017

Arms and Interventions

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 Name: trofinetide
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 flavoring

Outcome Measures

Primary Outcome Measures :

1. Adverse events [ Time Frame: 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 :

1. Motor Behaviour Assessment Scale (MBA) [ Time Frame: Through study completion, an average of 11 weeks ]
2. Clinical Global Impression of Improvement (CGI-I) [ Time Frame: Through study completion, an average of 11 weeks ]
3. Caregiver Top 3 Concerns via a Visual Analogue Scale (VAS) [ Time Frame: Through study completion, an average of 11 weeks ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

University of Alabama

Birmingham, Alabama, United States, 35233

United States, California

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States, 94609

University of California, San Diego

San Diego, California, United States, 92093

United States, Colorado

Children's Hosptial Colorado

Aurora, Colorado, United States, 80045

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

United States, Massachusetts

Boston Children's Hospital

Boston, Massachusetts, United States, 02115

United States, Minnesota

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, United States, 55101

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

United States, South Carolina

Greenwood Genetic Center

Greenwood, South Carolina, United States, 29646

United States, Tennessee

Vanderbilt University

Nashville, Tennessee, United States, 37235

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

Sponsors and Collaborators

Neuren Pharmaceuticals Limited

rettsyndrome.org

Investigators

• Principal Investigator: Daniel Glaze, MD; Baylor College of Medicine
• Principal Investigator: Alan Percy, MD; University of Alabama at Birmingham
• Principal Investigator: Timothy Feyma, MD; Gillette Children's Specialty Healthcare
• 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: Steve Skinner, MD; Greenwood Genetic Center
• 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

More Information

• Responsible Party: Neuren Pharmaceuticals Limited
• ClinicalTrials.gov Identifier: NCT02715115
• Other Study ID Numbers: Neu-2566-RETT-002
• First Posted: March 22, 2016
• Last Update Posted: August 14, 2020
• Last Verified: August 2020

Keywords provided by Neuren Pharmaceuticals Limited:

Autism; Rett's syndrome; Rett disorder; Rett's disorder; Ataxia

Additional relevant MeSH terms:

Rett Syndrome; Syndrome; Disease; Pathologic Processes; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System