Rett SyndromePhase 2NCT02715115
A Safety Study of NNZ-2566 in Pediatric Rett Syndrome
A Phase 2 study testing NNZ-2566 in people with Rett Syndrome, run by Neuren Pharmaceuticals Limited at 12 sites in United States.
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 children and adolescents. Read more about this study
- Who is it for?
- Ages 5 to 15 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
- 82 participants
- Where
- 12 sitesUnited States
- Study dates
- Mar 2016to 5 Jan 2017
- 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 5 to 15 years
- Women only
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Children's Hosptial Colorado
Aurora, Colorado, 80045
University of Alabama
Birmingham, Alabama, 35233
Boston Children's Hospital
Boston, Massachusetts, 02115
Rush University Medical Center
Chicago, Illinois, 60612
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Greenwood Genetic Center
Greenwood, South Carolina, 29646
Baylor College of Medicine
Houston, Texas, 77030
Vanderbilt University
Nashville, Tennessee, 37235
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Gillette Children's Specialty Healthcare
Saint Paul, Minnesota, 55101
University of California, San Diego
San Diego, California, 92093
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Dose-ranging Study of the Safety and Pharmacokinetics of Oral NNZ-2566 in Pediatric 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 children and adolescents.
Read the 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.
- 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
Also called trofinetide
Glycyl-L-2-Methylpropyl-L-Glutamic Acid (NNZ-2566) supplied as a lyophilized powder for reconstitution with strawberry flavored solution 0.5% v/v in Water for Injection.
PlaceboDrug
Also called Strawberry flavoring
Strawberry flavored solution and Water for Injection
| Study group | Role | What they receive |
|---|---|---|
| NNZ-2566 | Experimental | Glycyl-L-2-Methylpropyl-L-Glutamic Acid Receives: Drug: NNZ-2566 |
| Placebo (strawberry flavored solution) | Placebo comparator | Strawberry 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.
Adverse events
Incidence of adverse events (AEs), including serious adverse events (SAEs), will be compared across the three NNZ-2566 doses and placebo. SAEs and AEs will be examined throughout the study.
Measured: Through study completion, an average of 11 weeks
Secondary outcomes (3)
Motor Behaviour Assessment Scale (MBA)
Measured: Through study completion, an average of 11 weeks
Clinical Global Impression of Improvement (CGI-I)
Measured: Through study completion, an average of 11 weeks
Caregiver Top 3 Concerns via a Visual Analogue Scale (VAS)
Measured: Through study completion, an average of 11 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2016 (estimated)
- Study startMar 2016
- Primary completion5 Jan 2017
- Study completion5 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rett SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neuren Pharmaceuticals Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- rettsyndrome.org
- Responsible party
- Sponsor
- Investigators
- Daniel Glaze, MD, Principal investigator, Baylor College of MedicineAlan Percy, MD, Principal investigator, University of Alabama at BirminghamTimothy Feyma, MD, Principal investigator, Gillette Children's Specialty HealthcarePeter Heydemann, MD, Principal investigator, Rush University Medical CenterJeff Neul, MD, Principal investigator, University of California, San DiegoTim Benke, MD, Principal investigator, Children's Hospital ColoradoMary Jones, MD, Principal investigator, UCSF Benioff Children's Hospital OaklandSteve Skinner, MD, Principal investigator, Greenwood Genetic Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02715115
- Sponsor's protocol ID
- Neu-2566-RETT-002
- Status last verified
- Aug 2020
- First submitted
- 21 Feb 2016
- Last updated
- 14 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
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 38363467Parent 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
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Dose-ranging Study of the Safety and Pharmacokinetics of Oral NNZ-2566 in Pediatric Rett Syndrome
- ClinicalTrials.gov ID
- NCT02715115
- Acronym / sponsor ID
- Neu-2566-RETT-002
- Conditions
- Rett Syndrome
- Keywords
- Autism, Rett's syndrome, Rett disorder, Rett's disorder, Ataxia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Neuren Pharmaceuticals LimitedIndustry (pharma, biotech, devices)
- Collaborators
- rettsyndrome.org
- Study start
- Mar 2016 (actual)
- Primary completion
- 5 Jan 2017 (actual)
- Study completion
- 5 Jan 2017 (actual)
- First posted
- 22 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NNZ-2566 | Experimental | Drug: NNZ-2566Glycyl-L-2-Methylpropyl-L-Glutamic Acid |
| Placebo (strawberry flavored solution) | Placebo comparator | Drug: PlaceboStrawberry flavored solution and Water for Injection |
Who may qualify
- Ages
- 5 to 15 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NNZ-2566Also: trofinetideGlycyl-L-2-Methylpropyl-L-Glutamic Acid (NNZ-2566) supplied as a lyophilized powder for reconstitution with strawberry flavored solution 0.5% v/v in Water for Injection. | Drug | NNZ-2566 |
| PlaceboAlso: Strawberry flavoringStrawberry flavored solution and Water for Injection | Drug | Placebo (strawberry flavored solution) |
Primary outcome
Adverse events
Time frame: Through study completion, an average of 11 weeks
Incidence of adverse events (AEs), including serious adverse events (SAEs), will be compared across the three NNZ-2566 doses and placebo. SAEs and AEs will be examined throughout the study.
3 secondary outcomes
Motor Behaviour Assessment Scale (MBA)
Time frame: Through study completion, an average of 11 weeks
Clinical Global Impression of Improvement (CGI-I)
Time frame: Through study completion, an average of 11 weeks
Caregiver Top 3 Concerns via a Visual Analogue Scale (VAS)
Time frame: Through study completion, an average of 11 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2020.
- Derived from this study: PubMed 38363467Darwish 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.
- Derived from this study: PubMed 37460385Parent 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Glaze, MD principal investigator
Baylor College of Medicine
Alan Percy, MD principal investigator
University of Alabama at Birmingham
Timothy Feyma, MD principal investigator
Gillette Children's Specialty Healthcare
12 sites in 1 country: see every site and its status.
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 12 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 4 inclusion and 13 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 14 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 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 study completion, an average of 11 weeks). 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 NCT02715115, 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 14 Aug 2020.