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Rett SyndromePhase 2NCT01703533

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

A Phase 2 study testing NNZ-2566 in people with Rett Syndrome, run by Neuren Pharmaceuticals Limited at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 16 to 45 years, women only
Conditions the study is for
Rett Syndrome
What is being tested?
NNZ-2566
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
67 participants
Where
3 sitesUnited States
Study dates
Mar 2013to Sep 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 45 years
  • Women only
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 20Show fewer
  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Alabama

    Birmingham, Alabama, 35294-0113

  • Baylor School of Medicine

    Houston, Texas, 77030

  • Gillette Children's Specialty Healthcare

    Saint Paul, Minnesota, 55101

Other trials in United States

About this study

Official title: A Phase II Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Escalation Study of NNZ-2566 in Rett Syndrome

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.

Read the 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
Being tested
NNZ-2566, Placebo
Keywords
Autism, Rett's Syndrome, Rett Disorder, Rett's Disorder, Ataxia
Medical subject headings
Rett Syndrome, Autistic Disorder, Ataxia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NNZ-2566Drug

    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.

  • PlaceboDrug

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

    Strawberry flavored solution and Water for Injection

Study groups in NCT01703533
Study groupRoleWhat they receive
NNZ-2566ExperimentalGlycyl-L-2-Methylpropyl-L-Glutamic Acid
Receives: Drug: NNZ-2566
Placebo (strawberry flavored solution)Placebo comparatorStrawberry flavored solution and Water for Injection
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Through to Day 40

Secondary outcomes (4)

  1. Change in EEG activity

    Absolute change in the number of spikes in the EEG per hour during the awake state will be calculated for each subject between baseline (pre-treatment), during treatment (Days 1 thru 4, 14 and 26) and after treatment (Day 40).

    Absolute change in the power of frequency bands in the EEG over an hour in the awake state as determined by the Fast Fourier method will be calculated for each subject between baseline (pre-treatment), during treatment (Days 1 thru 4, 14 and 26) and after treatment (Day 40).

    Changes in the frequency of the characteristic repetitive stereotypic hand movements during wakefulness will be calculated for each subject between baseline (pre-treatment), during treatment (Days 1 thru 4, 14 and 26) and after treatment (Day 40).

    Measured: Baseline through to Day 40

  2. Behavior

    The following measures will be assessed at baseline and Day 26 and the changes compared between active and placebo groups:

    Symptom severity according to the Rett Syndrome Natural History Motor Behavior Assessment (MBA), Clinical Severity Scale (CSS), Aberrant Behavior Checklist (ABC), Vineland Adaptive Behavior Scale (VABS), and Clinical Global Impression of Severity (CGI-S).

    The following assessments will be undertaken at the additional time points specified: CGI-S (screening, baseline, Days 5, 14, 26, and 40), CGI-I (Days 5, 14, 26, and 40), MBA (Baseline, Days 26 and 40), CSS (screening, baseline, Days 26, and 40).

    Measured: Baseline through to Day 40

  3. Physiological changes

    Changes in autonomic function, i.e. respiratory rhythm, hyperventilation, apneas, oxygen desaturation, and heart rate variation will be calculated between baseline (pre-treatment), during treatment (Days 1 thru 4, 14 and 26) and after treatment (Day 40).

    Measured: Baseline through to Day 40

  4. Global and Functional outcome Measures

    Global outcome as measured by the change in scores on the Rett Syndrome Clinical Severity Score (CSS), The Rett Syndrome Motor-Behavior Assessment Scale (MBA), and the Clinical Global Impression - Severity and Improvement scales (CGI-S and -I) from baseline, during treatment, and post treatment.

    Changes in caregiver assessment of the top three causes for concern as assessed via a Visual Analogue Scale (VAS) will be evaluated for each subject between baseline (pre-treatment), during treatment (Day 26) and after treatment (Day 40).

    Changes in the Aberrant Behavior Checklist (ABC) and Vineland Adaptive Behavior Scales (VABS) will be calculated for each subject between baseline (pre-treatment), and during treatment (Day 26).

    Measured: Baseline through to Day 40

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Oct 2012 (estimated)
  2. Study startMar 2013
  3. Primary completionSep 2014
  4. Study completionSep 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
67 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01703533
Sponsor's protocol ID
Neu-2566-RETT-001
Status last verified
Jan 2018
First submitted
4 Oct 2012
Last updated
5 Feb 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 38363467

  • 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.

    PubMed 37460385

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NNZ-2566 in people with Rett Syndrome, run by Neuren Pharmaceuticals Limited at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events (time frame: Through to Day 40). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01703533, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2018.

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