Fragile X SyndromePhase 2NCT01894958
A Safety Study of NNZ-2566 in Patients With Fragile X Syndrome
A Phase 2 study testing NNZ-2566 in people with Fragile X Syndrome, run by Neuren Pharmaceuticals Limited at 17 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 Fragile X Syndrome in adolescent and adult males. Read more about this study
- Who is it for?
- Ages 12 to 45 years, men only
- Conditions the study is for
- Fragile X 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
- 72 participants
- Where
- 17 sitesUnited States
- Study dates
- Jan 2014to Oct 2015
- 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 12 to 45 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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.
- Current treatment with no more than 3 psychotropic medications. This includes medications used to treat problems with sleep onset and sleep continuity. Melatonin for difficulties with sleep onset is permissible and is excepted from the count of psychotropic medications. Similarly, anti-epileptic medications are permitted and are not denoted as "psychotropic medications" if they are used for treatment of seizures. Use of anti-epileptics for other indications such as the treatment of mood disorders counts towards the limit of permitted medications. Concurrent use of omega-3 fatty acids is also permissible and does not count towards the allowed number of concomitant psychotropic medications. A complete list of permitted concomitant psychotropic medications can be found in Appendix A.
- Concomitant medications for chronic medical conditions are permissible. Examples of chronic medical conditions include gastroesophageal reflux disease (GERD) and asthma. Every effort should be made to keep the doses and dosing regimens of these medications stable in the 4 weeks preceding Screening and during the period between Screening and the commencement of study medication.
- Permitted psychotropic concomitant medications (except for anti-epileptic medications-see below) must be stable, in terms of dose and dosing regimen, for at least 4 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication.
- Anti-epileptic medications must be at a stable dose and dosing regimen for 12 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication
- Behavioral treatments excluding psychotherapy (see exclusion criteria) must be stable for 4 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication
- 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.
Who cannot join
- 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.
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- 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.
- QT/QTcF Exclusions (any of the following):
- 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.
- QT/QTcF prolongation previously or currently controlled with medication, in which normal QT/QTcF intervals could or can only be achieved with medication
- Current treatment with other medications that have demonstrated QT/QTc prolongation and have this risk described in the Warnings and Precautions section of their Prescribing Information
- Patients with significant hearing and/or visual impairments that may affect their ability to complete the test procedures.
- Current treatment with insulin
- Hgb A1C values outside of the normal reference range at Screening
- Current or past treatment with insulin like growth factor IGF-1
- Current or past treatment with growth hormone
- Enrollment in another clinical trial within the 30 days preceding Screening
- Previously randomized in this clinical trial
- Allergy to strawberry
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
University of Michigan
Ann Arbor, Michigan, 48109
Emory University
Atlanta, Georgia, 30033
Kennedy Krieger Institute
Baltimore, Maryland, 21205
Rush University Medical Center
Chicago, Illinois, 60612
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Children's Hospital Colorado
Denver, Colorado, 80045
Greenwood Genetic Center
Greenwood, South Carolina, 29646
Texas Children's Hospital
Houston, Texas, 77030
Autism & Developmental Medicine Institute Geisinger Health System
Lewisburg, Pennsylvania, 17837
Suburban Research Associates
Media, Pennsylvania, 19063
Vanderbilt University Medical Center
Nashville, Tennessee, 37235
Mount Sinai School of Medicine
New York, New York, 10029
University of Nebraska
Omaha, Nebraska, 68588
UC Davis MIND Institute
Sacramento, California, 95817
Seattle Children's Hospital
Seattle, Washington, 98105
Children's National Hospital
Washington D.C., District of Columbia, 20010
University of Massachusetts Medical School
Worcester, Massachusetts, 01655
About this study
Official title: A Phase II Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dose Study of NNZ-2566 in Fragile X Syndrome
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.
Read the detailed description
Fragile X Syndrome is a genetically determined neurological disorder in which affected individuals are intellectually handicapped to varying degrees and display a variety of associated psychiatric symptoms. Clinically, Fragile X Syndrome is characterized by intellectual handicap, hyperactivity and attentional problems, autism spectrum symptoms, emotional lability and epilepsy. The epilepsy seen in Fragile X Syndrome is most commonly present in childhood, but then gradually remits towards adulthood. Physical features such as prominent ears and jaw, and hyper-extensibility of joints are frequently present but are not diagnostic. Intellectual handicap is the most common feature defining the phenotype. Treatment for the disorder is symptomatic - focusing on the management of symptoms - and supportive, requiring a multidisciplinary approach.
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 males with Fragile X Syndrome. The study also will also investigate measures of efficacy during treatment.
- Conditions
- Fragile X Syndrome
- Being tested
- NNZ-2566, Placebo
- Keywords
- Fragile X disorder, Autism
- Medical subject headings
- Fragile X Syndrome, Autistic Disorder
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 or 3g in 30mL bottles) 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
| 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 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 (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.
Measured: Through to Day 56
Secondary outcomes (3)
Physiological changes
Serum levels and changes of standard hematology, and chemistry parameters (including thyroid function) will be calculated from Baseline through to Day 56. Fundoscopy and tonsil size will be documented at Baseline, and Days 14, 28, 42 and 56. Flow cytometry will be used to assess the phosphorylation status of the enzymes Akt and extracellular signal-regulated kinase (ERK) in peripheral lymphocytes, on blood samples obtained on Days 14, 28, 42 and 56. Electrocardiogram (ECG) will be assessed at Screening, Days 14, 21, 28, 35, 42 and 56.
Measured: Baseline through to Day 56
Behavior
Symptom severity according to the Fragile X Symptom Rating Scale, Clinician Domain Specific Top Three Concerns-VAS, Aberrant Behavior Checklist (ABC), Vineland Adaptive Behavior Scale (VABS), Child and Adolescent Symptom Inventory-Anxiety Scale (CASI-16), Children's Yale-Brown Obsessive Compulsive Scale (CYBOCS-PDD), Expressive Language Sampling and Clinical Global Impression of Severity (CGI-S).
Measured: Baseline through to Day 56
Global and Functional outcome Measures
Global outcome as measured by the change in scores in the Clinical Global Impression - Severity and Improvement scales (CGI-S and -I) and the KiTap measure of cognition from baseline, during treatment, and post treatment.
Global and Functional outcome as measured by changes in scores in the Fragile X Symptom Rating Scale, Clinician Domain Specific Top Three Concerns-VAS, Caregiver Top Three Concerns (related to the subject's Fragile X syndrome) as assessed via a Visual Analogue Scale (VAS), CASI-20, CYBOCS-PDD, Aberrant Behavior Checklist (ABC), Vineland Adaptive Behavior Scales (VABS) and Expressive Language Sampling will be assessed during treatment.
Measured: Baseline through to Day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2013 (estimated)
- Study startJan 2014
- Primary completionSep 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fragile X 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
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neuren Pharmaceuticals Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Elizabeth M Berry-Kravis, MD, Principal investigator, Rush University Medical CenterJoseph Cubells, MD, PhD, Principal investigator, Emory UniversityAlexander Kolevzon, MD, Principal investigator, Icahn School of Medicine at Mount SinaiNicole Tartaglia, MD, Principal investigator, Children's Hospital ColoradoJean Frazier, MD, Principal investigator, University of Massachusetts, WorcesterShivkumar Hatti, MD, Principal investigator, Suburban Research AssociatesCraig Erickson, MD, Principal investigator, Children's Hospital Medical Center, CincinnatiThomas Challman, MD, Principal investigator, Autism & Developmental Medicine Institute Geisinger Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01894958
- Sponsor's protocol ID
- Neu-2566-FXS-001
- Status last verified
- Jan 2018
- First submitted
- 3 Jul 2013
- Last updated
- 5 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 32660869
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dose Study of NNZ-2566 in Fragile X Syndrome
- ClinicalTrials.gov ID
- NCT01894958
- Acronym / sponsor ID
- Neu-2566-FXS-001
- Conditions
- Fragile X Syndrome
- Keywords
- Fragile X disorder, Autism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Neuren Pharmaceuticals LimitedIndustry (pharma, biotech, devices)
- Study start
- Jan 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 10 Jul 2013 (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 Fragile X Syndrome in adolescent and adult males.
Detailed description
Fragile X Syndrome is a genetically determined neurological disorder in which affected individuals are intellectually handicapped to varying degrees and display a variety of associated psychiatric symptoms. Clinically, Fragile X Syndrome is characterized by intellectual handicap, hyperactivity and attentional problems, autism spectrum symptoms, emotional lability and epilepsy. The epilepsy seen in Fragile X Syndrome is most commonly present in childhood, but then gradually remits towards adulthood. Physical features such as prominent ears and jaw, and hyper-extensibility of joints are frequently present but are not diagnostic. Intellectual handicap is the most common feature defining the phenotype. Treatment for the disorder is symptomatic - focusing on the management of symptoms - and supportive, requiring a multidisciplinary approach.
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 males with Fragile X Syndrome. The study also will also investigate measures of efficacy 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 |
Who may qualify
- Ages
- 12 to 45 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (23 listed)
- Fragile X Syndrome with a molecular genetic confirmation of the full FMR1 mutation.
- 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.
- Current treatment with no more than 3 psychotropic medications. This includes medications used to treat problems with sleep onset and sleep continuity. Melatonin for difficulties with sleep onset is permissible and is excepted from the count of psychotropic medications. Similarly, anti-epileptic medications are permitted and are not denoted as "psychotropic medications" if they are used for treatment of seizures. Use of anti-epileptics for other indications such as the treatment of mood disorders counts towards the limit of permitted medications. Concurrent use of omega-3 fatty acids is also permissible and does not count towards the allowed number of concomitant psychotropic medications. A complete list of permitted concomitant psychotropic medications can be found in Appendix A.
Key exclusion criteria (23 listed)
- 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.
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-2566Glycyl-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. | Drug | NNZ-2566 |
| PlaceboAlso: Strawberry flavored solution 0.5% v/v in Water for InjectionStrawberry flavored solution | Drug | Placebo (strawberry flavored solution) |
Primary outcome
Adverse events
Time frame: Through to Day 56
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.
3 secondary outcomes
Physiological changes
Time frame: Baseline through to Day 56
Behavior
Time frame: Baseline through to Day 56
Global and Functional outcome Measures
Time frame: Baseline through to Day 56
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 5 Feb 2018.
- Derived from this study: PubMed 32660869Berry-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.
- Genetics Home ReferenceLink provided by the sponsor.
- Fragile X SyndromeLink provided by the sponsor.
- MECP2 duplication syndromeLink provided by the sponsor.
- PPM-X syndromeLink provided by the sponsor.
- Renpenning syndromeLink provided by the sponsor.
- tetrasomy 18pLink provided by the sponsor.
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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.
Elizabeth M Berry-Kravis, MD principal investigator
Rush University Medical Center
Joseph Cubells, MD, PhD principal investigator
Emory University
Alexander Kolevzon, MD principal investigator
Icahn School of Medicine at Mount Sinai
17 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 Fragile X Syndrome, run by Neuren Pharmaceuticals Limited at 17 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 23 inclusion and 23 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 17 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 56). 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 NCT01894958, which also lists 1 linked publication.
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.