A Safety Study of NNZ-2566 in Patients With Rett Syndrome

NCT01703533 | Completed Phase 2 DMC

• 1 other identifier: Neu-2566-RETT-001
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 3

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 adolescent and adult females.

Conditions

Rett Syndrome

Keywords

Autism; Rett's Syndrome; Rett Disorder; Rett's Disorder; Ataxia

Outcome Measures

Primary Outcomes (1)

• Adverse events

  Incidence of adverse events (AE), including Serious adverse events (SAE), will be evaluated between the two NNZ-2566 doses and placebo. SAEs will be examined from randomization through to Day 40. AEs will be examined from dosing through to Day 40.

  Through to Day 40

Secondary Outcomes (4)

• Change in EEG activity

  Baseline through to Day 40

• Behavior

  Baseline through to Day 40

• Physiological changes

  Baseline through to Day 40

• Global and Functional outcome Measures

  Baseline through to Day 40

Other Outcomes (1)

• Pharmacokinetics

  Baseline through to Day 40

Study Arms (2)

NNZ-2566

EXPERIMENTAL

Glycyl-L-2-Methylpropyl-L-Glutamic Acid

Drug: NNZ-2566

Placebo (strawberry flavored solution)

PLACEBO COMPARATOR

Strawberry flavored solution and Water for Injection

Drug: Placebo

Interventions

NNZ-2566 DRUG

Glycyl-L-2-Methylpropyl-L-Glutamic Acid (NNZ-2566) supplied as a lyophilized powder (2g in 50mL vials) for reconstitution with strawberry flavored solution 0.5% v/v in Water for Injection.

NNZ-2566

Placebo DRUG

Strawberry flavored solution and Water for Injection

Also known as: Strawberry flavored solution 0.5% v/v in Water for Injection

Placebo (strawberry flavored solution)

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of Rett Syndrome with proven mutation of the MeCP2 gene
• Age 16 to 45 years
• Severity rating of between 10 and 36 (Rett Syndrome Natural History/Clinical Severity Scale)
• Concomitant medications must be stable for \>4 weeks prior to enrollment. The following concomitant medications are permitted: anticonvulsants which do not have liver inducing effects; beta-blockers; medications for the treatment of gastroesophageal reflux disease (GERD); medications for the treatment of chronic respiratory conditions such as asthma; medications for the treatment of anxiety, of depression and of psychosis, hormonal contraceptives. Melatonin for difficulties with sleep onset.
• Ability to swallow study medication provided as a liquid solution, or via gastrostomy tube

You may not qualify if:

• No detectable abnormality of the EEG during screening period
• Actively undergoing regression
• Current treatment with insulin
• Hgb A1C values outside the normal reference range at screening
• Current or past treatment with IGF-1
• Current or past treatment with growth hormone
• Current treatment with N-methyl-D-aspartate (NMDA) antagonists
• Current or planned use of non-medication based interventional therapy during the period of the study (defined as 4-6 week screening period followed by 4 week dosing and 2 week follow-up period)
• Current clinically significant cardiovascular, renal, hepatic or respiratory disease
• Gastrointestinal disease which may interfere with the absorption, distribution, metabolism or excretion of the the study medication
• History of, or current cerebrovascular disease or brain trauma
• History of, or current significant endocrine disorder e.g. hypo or hyperthyroidism or diabetes mellitus
• History of, or current malignancy
• Clinically significant abnormalities in safety laboratory tests, vital signs or ECG, as measured at screening or baseline
• Confirmed pregnancy

Sponsors & Collaborators

• Neuren Pharmaceuticals Limited: lead
• Baylor College of Medicine: collaborator
• International Rett Syndrome Foundation: collaborator

Study Sites (3)

University of Alabama

Birmingham, Alabama, 35294-0113, United States

Location

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, 55101, United States

Location

Baylor School of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Darwish M, Passarell J, Youakim JM, Bradley H, Bishop KM. Exposure-Response Efficacy Modeling to Support Trofinetide Dosing in Individuals with Rett Syndrome. Adv Ther. 2024 Apr;41(4):1462-1480. doi: 10.1007/s12325-024-02796-y. Epub 2024 Feb 16.

  PMID: 38363467 DERIVED

• Parent H, Ferranti A, Niswender C. Trofinetide: a pioneering treatment for Rett syndrome. Trends Pharmacol Sci. 2023 Oct;44(10):740-741. doi: 10.1016/j.tips.2023.06.008. Epub 2023 Jul 16.

  PMID: 37460385 DERIVED

MeSH Terms

Conditions

Rett Syndrome; Autistic Disorder; Ataxia

Interventions

trofinetide; Water; Injections

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Dyskinesias; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Daniel G Glaze, M.D.

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Jeffrey L Neul, M.D., Ph.D.

  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

• Arthur Beisang, MD

  Gillette Children's Specialty Healthcare

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2012
• First Posted: October 10, 2012
• Study Start: March 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: February 5, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)