A Safety Study of NNZ-2566 in Patients With Fragile X Syndrome

NCT01894958 | Completed Phase 2 DMC

• 1 other identifier: Neu-2566-FXS-001
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 17

Brief Summary

The purpose of this study is to determine whether NNZ-2566 is safe and well tolerated in the treatment of Fragile X Syndrome in adolescent and adult males.

Conditions

Fragile X Syndrome

Keywords

Fragile X disorder; Autism

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. Incidence of AEs from randomized dosing through to Day 56 post randomization. Incidence of SAEs from randomization through to Day 56 post randomization.

  Through to Day 56

Secondary Outcomes (3)

• Physiological changes

  Baseline through to Day 56

• Behavior

  Baseline through to Day 56

• Global and Functional outcome Measures

  Baseline through to Day 56

Other Outcomes (2)

• Pharmacokinetics

  During treatment

• Computerized eye-tracking

  Baseline through to Day 56

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

Drug: Placebo

Interventions

NNZ-2566 DRUG

Glycyl-L-2-Methylpropyl-L-Glutamic Acid (NNZ-2566) supplied as a lyophilized powder (2g in 50mL vials or 3g in 30mL bottles) for reconstitution with strawberry flavored solution 0.5% v/v in Water for Injection.

NNZ-2566

Placebo DRUG

Strawberry flavored solution

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

Placebo (strawberry flavored solution)

Eligibility Criteria

• Age: 12 Years - 45 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Fragile X Syndrome with a molecular genetic confirmation of the full FMR1 mutation.
• Results from previously completed testing are acceptable with written documentation of the genetic results.
• Results from PCR or Southern blot tests are acceptable
• Results from cytogenetic testing are not acceptable but subject may be eligible if molecular genetic testing is redone.
• A full mutation with mosaicism is allowed if:
• Subject manifests full phenotypic profile of Fragile X syndrome
• CGG Repeats \>200 are detected
• Southern blot prevails over PCR, if Southern blot shows \>200 repeats and PCR results show \<200 repeats.
• The following results would not meet criteria:
• Deletions
• Point mutations
• Mosaicism without detection of \>200 CGG repeats or absence of full phenotypic profile in an individual with mosaicism
• Males, aged 12-45 years
• Subjects with a Clinical Global Impression - Severity (CGI-S) score of 4 or greater at Screening
• Subjects with a total score of 30 or greater on the Aberrant Behavior Checklist (ABC) at Screening.

You may not qualify if:

• a. For each enrollee, every effort should be made to maintain stable regimens of allowed concomitant medications and allowed behavioral therapies from the time of commencement of single-blind study medication until the last study assessment.
• Sufficient expressive language capabilities to complete the Expressive Language Sampling Task.
• Individuals with a history of seizures should have a stable pattern of seizure activity in the 3 months preceding Screening.
• Treatment within the two weeks prior to Screening with monoamine (MAO) inhibitors, lithium, minocycline, acamprosate, racemic baclofen, investigational metabotropic glutamate receptor subtype 5 (mGluR5) medications, d-cycloserine, oxytocin, carbetocin, tricyclic antidepressants and bupropion.
• Patients planning to commence psychotherapy, including cognitive behavior therapy (CBT), during the period of the study or those who had begun psychotherapy, including CBT, within 6 weeks prior to Screening.
• History of, or current, cardiovascular, renal, hepatic, respiratory and/or gastrointestinal disease, which may interfere with the absorption, distribution, metabolism or excretion of the study medication, or which may interfere with the interpretation of the safety/tolerability or efficacy of the study medication.
• History of, or current cerebrovascular disease or clinically significant brain trauma.
• History of, or current clinically significant endocrine disorder, e.g. hypo or hyperthyroidism, or diabetes.
• History of, or current malignancy.
• Current major depressive disorder (patients have to be free of the most recent episode for 3 months prior to enrollment).
• History of a DSM-5-defined substance use disorder in the 3 months prior to Screening.
• Clinically significant abnormalities in safety laboratory tests, vital signs or ECG, as measured at Screening.
• QTcF \> 450 msec. Three ECGs should be obtained at the time of Screening, 5 minutes apart from each other, and the results should be averaged.
• History of risk factors for torsade de pointes (e.g. heart failure, clinically significant hypokalemia or hypomagnesemia, or a family of long QT syndrome).
• A serum potassium at screening \<3.0 mmol/L.

Sponsors & Collaborators

• Neuren Pharmaceuticals Limited: lead

Study Sites (17)

UC Davis MIND Institute

Sacramento, California, 95817, United States

Location

Children's Hospital Colorado

Denver, Colorado, 80045, United States

Location

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Emory University

Atlanta, Georgia, 30033, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Nebraska

Omaha, Nebraska, 68588, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Autism & Developmental Medicine Institute Geisinger Health System

Lewisburg, Pennsylvania, 17837, United States

Location

Suburban Research Associates

Media, Pennsylvania, 19063, United States

Location

Greenwood Genetic Center

Greenwood, South Carolina, 29646, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37235, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• Berry-Kravis E, Horrigan JP, Tartaglia N, Hagerman R, Kolevzon A, Erickson CA, Hatti S, Snape M, Yaroshinsky A, Stoms G; FXS-001 Investigators; Glass L, Jones NE. A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Fragile X Syndrome. Pediatr Neurol. 2020 Sep;110:30-41. doi: 10.1016/j.pediatrneurol.2020.04.019. Epub 2020 May 23.

  PMID: 32660869 DERIVED

Related Links

• Genetics Home Reference
• Fragile X Syndrome
• MECP2 duplication syndrome
• PPM-X syndrome
• Renpenning syndrome
• tetrasomy 18p
• MedlinePlus
• Drinking Water
• Fragile X Syndrome
• U.S. FDA Resources

MeSH Terms

Conditions

Fragile X Syndrome; Autistic Disorder

Interventions

trofinetide; Water; Injections

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Elizabeth M Berry-Kravis, MD

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

• Joseph Cubells, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

• Alexander Kolevzon, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Nicole Tartaglia, MD

  Children's Hospital Colorado

  PRINCIPAL INVESTIGATOR

• Jean Frazier, MD

  University of Massachusetts, Worcester

  PRINCIPAL INVESTIGATOR

• Shivkumar Hatti, MD

  Suburban Research Associates

  PRINCIPAL INVESTIGATOR

• Craig Erickson, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Thomas Challman, MD

  Autism & Developmental Medicine Institute Geisinger Health System

  PRINCIPAL INVESTIGATOR

• Kevin Sanders, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Diane Treadwell-Deering, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Jeffrey Innis, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Howard Needleman, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

• Steve Skinner, MD

  Greenwood Genetic Center

  PRINCIPAL INVESTIGATOR

• Bryan King, MD

  Seattle Children's Hospital

  PRINCIPAL INVESTIGATOR

• Randi Hagerman, MD

  UC Davis MIND Institute

  PRINCIPAL INVESTIGATOR

• Robert Findling, MD

  Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

  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: July 3, 2013
• First Posted: July 10, 2013
• Study Start: January 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: October 1, 2015
• Last Updated: February 5, 2018

Record last verified: 2018-01

Locations

US (17)