Fragile X Syndrome Clinical Trial
Official title:
A Randomized, Double-blind, Placebo-controlled, 2-period Crossover Study of BPN14770 in Adult Males With Fragile X Syndrome
Verified date | December 2020 |
Source | Tetra Discovery Partners |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This is a single-center, randomized, double-blind, 2-period crossover study to explore the effects of BPN14770 on cognitive function and behavior in subjects with Fragile X Syndrome. Subjects will receive both active treatment with BPN14770 capsules and matching placebo capsules in the course of the study. One treatment will be administered during each of the 12-week study periods.
Status | Completed |
Enrollment | 30 |
Est. completion date | July 31, 2020 |
Est. primary completion date | July 31, 2020 |
Accepts healthy volunteers | No |
Gender | Male |
Age group | 18 Years to 45 Years |
Eligibility | Inclusion Criteria: 1. Subject is male aged 18 to 45 years, inclusive. 2. Subject has Fragile X Syndrome with a molecular genetic confirmation of the full Fragile X Mental Retardation (FMR1) mutation (=200 CGG repetitions). 3. Current treatment with no more than 3 prescribed psychotropic medications. Anti- epileptic medications are permitted and are not counted as psychotropic medications if they are used for treatment of seizures. Anti-epileptics for other indications, such as the treatment of mood disorders, count towards the limit of permitted medications. 4. Permitted concomitant psychotropic medications must be at a stable dose and dosing regimen for at least 2 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication. 5. 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. 6. Subjects with a history of seizure disorder who are currently receiving treatment with anti-epileptics must have been seizure-free for 3 months preceding Screening, or must be seizure-free for 3 years if not currently receiving anti-epileptics. 7. Behavioral and therapy treatments/interventions must be stable for 4 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication, and throughout the study. Minor changes in hours or times of therapy that are not considered clinically significant will not be exclusionary. Changes in therapies provided through a school program, due to school vacations, are allowed. 8. Subject must be willing to practice barrier methods of contraception while on study, if sexually active. Abstinence is also considered a reasonable form of birth control in this study population. 9. Subject has a parent, legal authorized guardian or consistent caregiver. 10. Subject and caregiver are able to attend the clinic regularly and reliably. 11. Subject is able to swallow tablets and capsules. 12. For subjects who are not their own legal guardian, subject's parent/legal authorized guardian is able to understand and sign an informed consent form to participate in the study. 13. If subject is his/her own legal guardian, he/she can understand and sign informed consent to participate in the study. 14. If subject is not their own legal guardian, the subject provides assent for participation in the study, if the subject has the cognitive ability to provide assent. Exclusion Criteria: 1. History of, or current cardiovascular, renal, hepatic, respiratory, gastrointestinal, psychiatric, neurologic, cerebrovascular, or other systemic disease that would place the subject at risk or potentially interfere with the interpretation of the safety, tolerability, or efficacy of the study medication. Common diseases such as mild hypertension, well-controlled type 2 diabetes mellitus (hemoglobin A1C [Hgb A1C] <6.5%), etc. are allowed per the investigator's judgment as long as they are stable and controlled by medical therapy that is constant for at least 4 weeks before randomization. 2. Renal impairment, defined as serum creatinine > 1.25 x ULN at screening 3. Hepatic impairment, defined as ALT or AST elevation > 2 x ULN at screening. Note: LFTs may be repeated after 1 week to evaluate return to acceptable limits; if LFTs remain elevated, subject is ineligible to participate. 4. Clinically significant abnormalities, in the investigator's judgment, in safety laboratory tests, vital signs, or ECG, as measured during Screening. 5. History of substance abuse within the past year, according to investigator assessment. 6. Significant hearing or visual impairment that may affect the subject's ability to complete the test procedures. 7. Concurrent major psychiatric condition (e.g., Major Depressive Disorder, Schizophrenia or Bipolar Disorder) as diagnosed by the investigator. Subjects with additional diagnosis of Autism Spectrum Disorder or Anxiety Disorder will be allowed. 8. Subject has active diseases that would interfere with participation, such as acquired immunodeficiency disorder, hepatitis C, hepatitis B, or tuberculosis. 9. Subject is planning to commence psychotherapy or cognitive behavior therapy (CBT) during the period of the study or had begun psychotherapy or CBT within 4 weeks prior to Screening. 10. Subject is related to anyone employed by the sponsor, investigator, or study staff. 11. Subject has BMI less than 18 or greater than 36. 12. Subject has participated in another clinical trial within the 30 days preceding Screening. |
Country | Name | City | State |
---|---|---|---|
United States | Rush University Medical Center | Chicago | Illinois |
Lead Sponsor | Collaborator |
---|---|
Tetra Discovery Partners |
United States,
Gurney ME, Cogram P, Deacon RM, Rex C, Tranfaglia M. Multiple Behavior Phenotypes of the Fragile-X Syndrome Mouse Model Respond to Chronic Inhibition of Phosphodiesterase-4D (PDE4D). Sci Rep. 2017 Nov 7;7(1):14653. doi: 10.1038/s41598-017-15028-x. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | NIH-TCB: NIH Toolbox Cognitive Battery for Intellectual Disabilities | A set of 7 cognition assessments administered on an iPad | Change from Baseline to Week 6 and Week 12 of each Period for each of 7 assessments | |
Other | KiTAP Test of Attentional Performance | A set of 4 subtests designed in the form of short games | Change from Baseline to Week 6 and Week 12 of each Period | |
Other | CGI-S: Clinical Global Impression-Severity | The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. | Change from Baseline to Week 6 and Week 12 of each Period | |
Other | CGI-I: Clinical Global Impression-Improvement | The CGI is a clinician-rated scale utilizing history from the caregiver and incorporating it into a clinical rating, first for severity, and then for clinical follow-up. The CGI-S will be used at the baseline assessment to judge symptom severity as 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; and 7 = Among the most extremely ill. The CGI-I will be used at the Week 8 and End of Treatment/Week 16 visits to judge the change in clinical impression as 1 = Very Much Improved; 2 = Much Improved; 3 = Minimally Improved; 4 = No Change; 5 = Minimally Worse; 6 = Much Worse; and 7 = Very Much Worse. | Change from Baseline to Week 6 and Week 12 of each Period | |
Other | VAS: Visual Analog Rating Scale | The VAS will be used to measure the severity of three specific behavioral symptoms targeted in this study: behavior problems, language abilities, and eating behavior. For each behavior the caregiver is instructed to mark their impression of the behavior at the baseline visit and again at the Week 8 and End of Treatment/Week 16 visits. The calculated distance in cm between the visit marks thereby demonstrates whether each behavior stayed the same, improved, or worsened during the study and by how much. The scale is from 0 cm (defined as "worst behavior") to 10 cm ("behavior not a problem"). | Change from Baseline to Week 6 and Week 12 of each Period | |
Other | ABC: Aberrant Behavior Checklist | The Aberrant Behavior Checklist (ABC) is a 58-item rating scale used to assess maladaptive behaviors across five original subscales: Irritability (15 items from 0-45), Social Withdrawal (16 items from 0-48), Stereotypy (7 items from 0-21), Hyperactivity (16 items from 0-48), Inappropriate Speech (4 items from 0-12). Additionally, Social Avoidance, a newly developed four-item subscale (from 0-12) of the ABC that captures core social avoidance aspects of Fragile X Syndrome is reported. All items on the ABC are rated from 0 (not at all a problem) to 3 (the problem is severe in degree). Higher scores indicate greater maladaptive behaviors. Differences between Baseline and Week 10 are used as an indicator of change. | Change from Baseline to Week 12 of each Period | |
Other | ADAMS: Anxiety, Depression, and Mood Scale | The ADAMS (Anxiety, Depression, and Mood Scale) is a 28-item behavior-based informant instrument designed to assess anxiety, depression and mood disorders in individuals with intellectual disability. Items are rated on a scale of 0 ("behavior has not occurred, or is not a problem") to 3 ("behavior occurs a lot, or is a severe problem"). The scale is composed of 5 factors which address: Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety and Obsessive/Compulsive Behavior. | Change from Baseline to Week 12 of each Period | |
Other | Vineland-3 Rating Scale | The VABS-III is a caregiver survey interview that measures the personal and social skills of individuals from birth through adulthood. It was designed to assess handicapped and non-handicapped persons in their personal and social functioning and is appropriate for individuals of all ages. The Adaptive Behavior Composite (ABC) score is calculated from the caregiver responses using age-adjusted scoring tables. ABC scores range from 20 to 160 and indicate low (20-70), moderately low (70-85), adequate (85-115), moderately high (115-130), or high (130-160) overall adaptive functioning. | Change from Baseline to 12 of each Period | |
Other | ERP: Event Related Potentials | An EEG (electroencephalogram) maps timing of a subject's responses to sounds heard in a headset. | Change from Baseline to Week 12 of each Period | |
Other | Eye Tracking | Subjects will view pictures shown on the screen. Each assessment begins with presentation of a scrambled face image followed immediately by its matched face image. Measurements include looking time to the eye region of interest (ROI), and number of fixations to the eye ROI, as well as pupil dilatation by pupilometry. | Change from Baseline Week 12 of each Period | |
Primary | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Number of subjects with treatment-related adverse events as assessed by MedDRA | up to 24 weeks |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05418049 -
Evaluating the Neurophysiologic and Clinical Effects of Single Dose Drug Challenge
|
Phase 2 | |
Enrolling by invitation |
NCT01364818 -
Brain Connectivity in Neurodevelopmental Disorders in Response to Treatment
|
N/A | |
Completed |
NCT00965432 -
A Single-Dose Study in Normal Volunteers to Assess the Safety, Tolerability and Pharmacokinetics of STX107
|
Phase 1 | |
Completed |
NCT01120626 -
Randomized Controlled Study of Donepezil in Fragile X Syndrome
|
Phase 2 | |
Completed |
NCT01204151 -
Teaching Math Skills to Individuals With Fragile X Syndrome
|
N/A | |
Active, not recruiting |
NCT00334971 -
Aromatase Activity and Ovarian Growth Factors in African-American Versus Caucasian Women
|
N/A | |
Enrolling by invitation |
NCT06139172 -
Promoting Prosocial Behavior in Syndromic Intellectual and Developmental Disabilities
|
N/A | |
Recruiting |
NCT04977986 -
Clinical Study of Cannabidiol in Children, Adolescents, and Young Adults With Fragile X Syndrome
|
Phase 3 | |
Active, not recruiting |
NCT04698551 -
NIPD on cffDNA for Triplet Repeat Diseases
|
||
Completed |
NCT03722290 -
Metformin in Children and Adults With Fragile X Syndrome
|
Phase 2 | |
Completed |
NCT05030129 -
Single Blind Study of Ergoloid Mesylates, 5-HTP and the Combination in Adult Males With Fragile X Syndrome
|
Phase 2 | |
Recruiting |
NCT05957549 -
Tracking Early Emergence of Sound Perception Impairments in FXS With Multimodal fNIRS/EEG
|
N/A | |
Recruiting |
NCT04141163 -
Metformin in Patients With Fragile X
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT06081348 -
Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
|
Phase 2 | |
Completed |
NCT00858689 -
Add-on Pilot Trial of Minocycline to Treat Fragile X Syndrome
|
N/A | |
Enrolling by invitation |
NCT03655223 -
Early Check: Expanded Screening in Newborns
|
||
Enrolling by invitation |
NCT03802799 -
Open Label Extension to Assess the Long-Term Safety and Tolerability of ZYN002 in Children and Adolescents With FXS
|
Phase 2/Phase 3 | |
Recruiting |
NCT05295277 -
Validation of Optical Genome Mapping for the Identification of Constitutional Genomic Variants in a Postnatal Cohort
|
||
Enrolling by invitation |
NCT03836300 -
Parent and Infant Inter(X)Action Intervention (PIXI)
|
N/A | |
Completed |
NCT01725152 -
Ganaxolone Treatment in Children With Fragile X Syndrome
|
Phase 2 |