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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
248
Phase 2b: Change from baseline in Total Cognition Composite Change Sensitive Score from the NIH-TCB
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.
Time frame: 8 weeks
Phase 2b: Change from baseline in EEG resting state relative power bands during rest
Resting-state EEG relative power changes from baseline are characterized by significant shifts in power bands such as gamma, alpha, theta and beta bands
Time frame: 8 weeks
Phase 3:Change from baseline in Total Cognition Composite score from the NIH-TCB
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.
Time frame: 12 weeks
Phase 2b: Change from baseline in Fluid Reasoning Composite Change Sensitive Scores from the NIH-TCB
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.
Time frame: 8 weeks
Phase 2b: Change from baseline in Flanker Scores from the NIH-TCB
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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
Time frame: 8 weeks
Phase 2b: Incidence, nature, and severity of adverse events (AEs) and serious adverse events (SAEs)
Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Time frame: 8 weeks
Phase 2b: Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) throughout the study
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
Time frame: 8 weeks
Phase 2b: The PK parameters of SPG601 concentrations in plasma-Cmax
Maximum concentration of SPG601 in plasma following dose
Time frame: 4 weeks
Phase 2b: The PK parameters of SPG601 concentrations in plasma-T 1/2
Metabolic half life of SPG601 in plasma following dose
Time frame: 4 weeks
Phase 3: Incidence, nature, and severity of adverse events (AEs) and serious adverse events (SAEs)
Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Time frame: 16 weeks
Phase 3: Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) throughout the study
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
Time frame: 8 weeks
Phase 3: Change from baseline in Flanker Scores from the NIH-TCB
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.
Time frame: 12 weeks
Phase 3: Change from baseline in Fluid Reasoning Composite Change Sensitive Scores from the NIH-TCB
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.
Time frame: 12 weeks
Phase 3: Change from baseline to week 4 and week 8 in Total Cognition Composite score from the NIH-TCB
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.
Time frame: 8 weeks
Phase 3: Change From Baseline in Behavioral Symptoms of Fragile X Syndrome Using the Aberrant Behavior Checklist (ABC) Total Score in Stratum
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.
Time frame: 12 weeks
Phase 3: Change from baseline to Week 12 in Vineland Adaptive Behavior Scale 3rd Edition
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.
Time frame: 12 weeks
Phase 3: Change from baseline in the Anxiety, Depression and Mood Scale (ADAMS)
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.
Time frame: 12 weeks
Phase 3: Change from baseline in behaviors and other symptoms on Numerical Rating System (NRS) by caregiver
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.'
Time frame: 12 weeks
Phase 3: Change from baseline in CGI-I as assessed by investigator
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")
Time frame: 12 weeks
Phase 3: Change from baseline in Caregiver Global Impression of Improvement (CaGI-I) assessments
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.
Time frame: 12 weeks
Phase 3: The PK parameters of SPG601 concentrations in plasma-Cmax
Maximum concentration in plasma following administration of SPG601
Time frame: 12 weeks
Phase 3: The PK parameters of SPG601 concentrations in plasma-T 1/2
Metabolic half life of SPG601 in plasma following dose
Time frame: 12 weeks
Phase 3 substudy: Change from baseline in the gamma range in response to the chirp stimulus and to the steady state stimuli
Auditory test will be evaluated for difference in responses to stimuli.
Time frame: 12 weeks
Phase 3 substudy: Change from baseline in EEG resting state relative power in the alpha, theta, and gamma bands during rest
Resting-state EEG relative power changes from baseline are characterized by significant shifts in power bands such as gamma, alpha, theta and beta bands
Time frame: 12 weeks