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

Tracking Information

• First Submitted Date: February 21, 2016
• First Posted Date: March 22, 2016
• Last Update Posted Date: August 14, 2020
• Actual Study Start Date: March 2016
• Actual Primary Completion Date: January 5, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 16, 2016)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 16, 2016)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Safety Study of NNZ-2566 in Pediatric Rett Syndrome
• Official Title: A Randomized, Double-blind, Placebo-controlled, Dose-ranging Study of the Safety and Pharmacokinetics of Oral NNZ-2566 in Pediatric Rett Syndrome
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rett 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.
  Other Name: trofinetide
• Drug: Placebo
  Strawberry flavored solution and Water for Injection
  Other Name: Strawberry flavoring

Study Arms

• Experimental: NNZ-2566
  Glycyl-L-2-Methylpropyl-L-Glutamic Acid
  Intervention: Drug: NNZ-2566
• Placebo Comparator: Placebo (strawberry flavored solution)
  Strawberry flavored solution and Water for Injection
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 14, 2016): 82
• Original Estimated Enrollment (submitted: March 16, 2016): 64
• Actual Study Completion Date: January 5, 2017
• Actual Primary Completion Date: January 5, 2017 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 5 Years to 15 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02715115
• Other Study ID Numbers: Neu-2566-RETT-002
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Neuren Pharmaceuticals Limited
• Original Responsible Party: Same as current
• Current Study Sponsor: Neuren Pharmaceuticals Limited
• Original Study Sponsor: Same as current
• Collaborators: 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

• PRS Account: Neuren Pharmaceuticals Limited
• Verification Date: August 2020