Fragile X Syndrome (FXS)
Conditions
Keywords
Fragile X Syndrome, Fragile X Chromosome, cognitive outcomes
Brief summary
This Phase 2b/3, randomized, double-blind, placebo-controlled, 2-part study will evaluate the efficacy, safety and tolerability of different dose regimens of SPG601 in adult male participants with Fragile X syndrome.
Detailed description
This is a Phase 2b/3, randomized, double-blind, placebo-controlled, study designed to evaluate the efficacy, safety and tolerability of multiple dose regimens of SPG601 in male participants with FXS. The study consists of two parts, Phase 2b, dose-regimen finding, 4-arm parallel design: Eligible participants will be randomized to receive SPG601 or matched placebo. Participants will receive study intervention over 4 weeks and will be followed up for 4 weeks after last dose of study intervention. Phase 3, 2-arm parallel design: Eligible participants will be randomized 1:1 to receive SPG601 or matched placebo. The dose of SPG601 administered in the Phase 3 will be defined based on analysis of Phase 2b. Participants will receive study intervention over 12 weeks and will be followed up for 4 weeks after last dose of study intervention.
Interventions
DRUGSPG601
synthetic small molecule
DRUGPlacebo
Placebo
Sponsors
Spinogenix
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Adult males aged 18 to 45 years, inclusive * Diagnosis of Fragile X as confirmed with genetic testing * Patient must have caregiver * Must be in good health with no significant medical history
Exclusion criteria
* Any physical or psychological condition that prohibits study completion * Uncontrolled seizures or history of epilepsy with a seizure in the past 6 months. * Auditory or visual impairments that cannot be corrected * History of suicidal behavior or suicidal ideation * Screening vital signs that are abnormal per protocol specification * ECG that are clinically significant abnormal * History of substance abuse or dependence within 6 months * Other investigational products within 30 days * Unable to swallow capsules
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 3:Change from baseline in Total Cognition Composite score from the NIH-TCB | 12 weeks | The NIH Toolbox (NIH-TCB) Total Cognition Composite Change-Sensitive Score (CSS) is used to measure cognitive change over time. It is calculated by combining the Crystallized Composite (reading/vocabulary) and Fluid Composite (memory/executive function/speed) scores. Higher scores indicate higher level of functioning. |
| Phase 2b: Change from baseline in Total Cognition Composite Change Sensitive Score from the NIH-TCB | 8 weeks | The NIH Toolbox (NIH-TCB) Total Cognition Composite Change-Sensitive Score (CSS) is used to measure cognitive change over time. Higher scores indicate higher level of functioning. The scores typically span across the developmental range, often extending well above and below the 500-point mark depending on the age and cognitive ability of the individual. |
| Phase 2b: Change from baseline in EEG resting state relative power bands during rest | 8 weeks | Resting-state EEG relative power changes from baseline are characterized by significant shifts in power bands such as gamma, alpha, theta and beta bands |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2b: Incidence, nature, and severity of adverse events (AEs) and serious adverse events (SAEs) | 8 weeks | Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) |
| Phase 2b: Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) throughout the study | 8 weeks | Prospective suicidality assessment is performed using the Columbia-Suicide Severity Rating Scale (C-SSRS), a questionnaire to evaluate suicidal ideation and behavior. Answer "yes" on item 4 or 5 of the Suicidal Ideation section or "yes" on any item of the Suicidal Behavior section is considered positive. Range is 2-25 |
| Phase 2b: The PK parameters of SPG601 concentrations in plasma-Cmax | 4 weeks | Maximum concentration of SPG601 in plasma following dose |
| Phase 2b: The PK parameters of SPG601 concentrations in plasma-T 1/2 | 4 weeks | Metabolic half life of SPG601 in plasma following dose |
| Phase 3: Incidence, nature, and severity of adverse events (AEs) and serious adverse events (SAEs) | 16 weeks | Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) |
| Phase 3: Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) throughout the study | 8 weeks | Prospective suicidality assessment is performed using the Columbia-Suicide Severity Rating Scale (C-SSRS), a questionnaire to evaluate suicidal ideation and behavior. Answer "yes" on item 4 or 5 of the Suicidal Ideation section or "yes" on any item of the Suicidal Behavior section is considered positive. Range is 2-25 |
| Phase 3: Change from baseline in Flanker Scores from the NIH-TCB | 12 weeks | Flanker Inhibitory control will assess inhibitory control and attention through asking participant to focus on one stimuli will not focusing on any stimuli surrounding it. |
| Phase 3: Change from baseline in Fluid Reasoning Composite Change Sensitive Scores from the NIH-TCB | 12 weeks | The Fluid Cognition Composite (FCC) from the NIH Toolbox Cognition Battery (NIHTB-CB) is designed to measure changes to neurological functioning. It combines scores from five tests (Dimensional Change Card Sort, Flanker, List Sorting, Pattern Comparison, and Picture Sequence Memory) to provide a measure of executive function, memory, and processing speed. Higher scores indicate higher level of functioning. Superior ability is 130, average is approx. 100 and less than 70 is impairment. |
| Phase 3: Change from baseline to week 4 and week 8 in Total Cognition Composite score from the NIH-TCB | 8 weeks | The NIH Toolbox (NIH-TCB) Total Cognition Composite Change-Sensitive Score (CSS) is used to measure cognitive change over time. It is calculated by combining the Crystallized Composite (reading/vocabulary) and Fluid Composite (memory/executive function/speed) scores. Higher scores indicate higher level of functioning. The scores typically span across the developmental range, often extending well above and below the 500-point mark depending on the age and cognitive ability of the individual. |
| Phase 3: Change From Baseline in Behavioral Symptoms of Fragile X Syndrome Using the Aberrant Behavior Checklist (ABC) Total Score in Stratum | 12 weeks | The Aberrant Behavior Checklist-Community edition (ABC-C) is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") The ABC will be scored using the FXS-specific factoring system (ABC-FX) for which the total score ranks from 0 to 165. |
| Phase 3: Change from baseline in the Anxiety, Depression and Mood Scale (ADAMS) | 12 weeks | Anxiety, Depression, and Mood Scale (ADAMS) scores is used assess inappropriate speech, irritability, hyperactivity, lethargy/withdrawal, stereotypy, and social avoidance versus baseline as reported by caregiver. The scale is composed of 5 factors, which address Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety, and Obsessive/Compulsive Behavior. |
| Phase 3: Change from baseline in behaviors and other symptoms on Numerical Rating System (NRS) by caregiver | 12 weeks | Numerical rating scale (NRS) scores based on patient-specific behaviors within the domains of Daily Function, Language, and Academic Skill. Caregiver will rate individual from 0 to 10, where 0 indicates 'worst problem' and 10 indicates' no problem at all.' |
| Phase 3: Change from baseline in CGI-I as assessed by investigator | 12 weeks | The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale used to assess treatment response. The score ranges from 1 to 7 (with 1 being "very much improved", 4 being "no change" to 7 being "very much worse") |
| Phase 3: Change from baseline in Caregiver Global Impression of Improvement (CaGI-I) assessments | 12 weeks | The Caregiver Global Impression of Improvement (CaGI-I) is a global measure to provide a caregiver's perspective of a subject's overall condition. The caregiver will use a 7-point scale to assess how the condition has changed from baseline. A higher number indicates worsening condition. |
| Phase 3: The PK parameters of SPG601 concentrations in plasma-Cmax | 12 weeks | Maximum concentration in plasma following administration of SPG601 |
| Phase 3: The PK parameters of SPG601 concentrations in plasma-T 1/2 | 12 weeks | Metabolic half life of SPG601 in plasma following dose |
| Phase 3 substudy: Change from baseline in the gamma range in response to the chirp stimulus and to the steady state stimuli | 12 weeks | Auditory test will be evaluated for difference in responses to stimuli. |
| Phase 3: Change from baseline to Week 12 in Vineland Adaptive Behavior Scale 3rd Edition | 12 weeks | Vineland-3 Adaptive Behavior Scale (Vineland-3), using the composite score and domain scores from communication, daily living skills, and socialization. The adaptive behavior composite standard score is computed from the sum of standard scores from the domains and converted into the adaptive behavior composite standard score. Higher scores indicate a higher adaptive level of functioning. |
| Phase 3 substudy: Change from baseline in EEG resting state relative power in the alpha, theta, and gamma bands during rest | 12 weeks | Resting-state EEG relative power changes from baseline are characterized by significant shifts in power bands such as gamma, alpha, theta and beta bands |
| Phase 2b: Change from baseline in Fluid Reasoning Composite Change Sensitive Scores from the NIH-TCB | 8 weeks | The Fluid Cognition Composite (FCC) from the NIH Toolbox Cognition Battery (NIHTB-CB) is designed to measure changes to neurological functioning. It combines scores from five tests (Dimensional Change Card Sort, Flanker, List Sorting, Pattern Comparison, and Picture Sequence Memory) to provide a measure of executive function, memory, and processing speed. Higher scores indicate higher level of functioning. Superior ability is 130, average is approx. 100 and less than 70 is impairment. |
| Phase 2b: Change from baseline in Flanker Scores from the NIH-TCB | 8 weeks | Flanker Inhibitory control will assess inhibitory control and attention through asking participant to focus on one stimuli will not focusing on any stimuli surrounding it. A higher score indicates better performance |
Contacts
CONTACTContact
Outcome results
None listed