Clinical trial NCT02715115: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rett Syndrome
Keywords: Autism
Rett's syndrome
Rett disorder
Rett's disorder
Ataxia
Lead sponsor: Neuren Pharmaceuticals Limited
Sponsor class: INDUSTRY
Collaborators: name: rettsyndrome.org
First posted: 2016-03-22
Enrollment: 82
Sex: FEMALE
Minimum age (years): 5
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Adverse events
timeFrame: Through study completion, an average of 11 weeks
Secondary outcomes:
measure: Motor Behaviour Assessment Scale (MBA)
timeFrame: Through study completion, an average of 11 weeks
measure: Clinical Global Impression of Improvement (CGI-I)
timeFrame: Through study completion, an average of 11 weeks
measure: Caregiver Top 3 Concerns via a Visual Analogue Scale (VAS)
timeFrame: Through study completion, an average of 11 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Aurora
country: United States
facility: Children's Hosptial Colorado
state: Colorado
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Saint Paul
country: United States
facility: Gillette Children's Specialty Healthcare
state: Minnesota
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Greenwood
country: United States
facility: Greenwood Genetic Center
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Daniel Glaze, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Alan Percy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Gillette Children's Specialty Healthcare
name: Timothy Feyma, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rush University Medical Center
name: Peter Heydemann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Jeff Neul, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Colorado
name: Tim Benke, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UCSF Benioff Children's Hospital Oakland
name: Mary Jones, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Greenwood Genetic Center
name: Steve Skinner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Children's Hospital
name: Mustafa Sahin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University
name: Sarika Peters, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Shannon Standridge
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Eric Marsh, MD
role: PRINCIPAL_INVESTIGATOR
References: