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

NCT ID: NCT01703533

Last Updated: 2018-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2014-09-30

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.

Detailed Description

Rett Syndrome is a developmental disorder primarily if not exclusively 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 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 and tolerability of treatment with oral administration of NNZ-2566 at 35 mg/kg or 70 mg/kg BID in adolescent or adult females with Rett Syndrome. The study also will also investigate measures of efficacy during treatment.

Conditions

Rett Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

NNZ-2566

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

Group Type: EXPERIMENTAL

NNZ-2566

Intervention Type: 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.

Placebo (strawberry flavored solution)

Strawberry flavored solution and Water for Injection

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Strawberry flavored solution and Water for Injection

Interventions

NNZ-2566

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.

Intervention Type: DRUG

Placebo

Strawberry flavored solution and Water for Injection

Intervention Type: DRUG

Other Intervention Names

Strawberry flavored solution 0.5% v/v in Water for Injection

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• No detectable abnormality of the EEG during screening period
• Actively undergoing regression
• QTcF exclusions (any of the following): baseline/screening QT/QTcF interval of 450 msec; history of risk factors for torsade de pointes (e.g. heart failure, hypokalemia (serum potassium at screening < 3.0 mmol/L) or family history of long QT syndrome; QT/QTcF prolongation previously or currently controlled with medication
• 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
• Significant hearing and/or visual impairment that may affect ability to complete the test procedures
• Enrollment in another clinical trial within the previous 30 days
• Previously randomized in this clinical trial
• Allergy to strawberries

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Baylor College of Medicine

OTHER

Sponsor Role: collaborator

International Rett Syndrome Foundation

OTHER

Sponsor Role: collaborator

Neuren Pharmaceuticals Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel G Glaze, M.D.

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Jeffrey L Neul, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Alan Percy, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Timothy Feyma, MD

Role: PRINCIPAL_INVESTIGATOR

Gillette Children's Specialty Healthcare

Arthur Beisang, MD

Role: PRINCIPAL_INVESTIGATOR

Gillette Children's Specialty Healthcare

Locations

University of Alabama

Birmingham, Alabama, United States

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, United States

Baylor School of Medicine

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 38363467 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37460385 (View on PubMed)

Other Identifiers

Neu-2566-RETT-001

Identifier Type: -

Identifier Source: org_study_id