A Study to Investigate the Effects and Safety of SPG601 for the Treatment of Fragile X Syndrome in Male Participants

A Phase 2b/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of SPG601 in Male Participants With Fragile X Syndrome

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Fragile X Syndrome (FXS)
• Intervention / Treatment: Drug: Placebo; Drug: SPG601

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.

• Study Type: Interventional
• Enrollment (Estimated): 248
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Contact; Phone Number: (503) 673-3842; Email: contact@spinogenix.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Phase 2b: Active comparator; Phase 2b: Active SPG601 to be administered to participants with Fragile X Syndrome Participants with Fragile X Syndrome will be randomized to receive SPG601 daily for 4 weeks	Drug: SPG601; synthetic small molecule
Placebo Comparator: Phase 2b: Placebo; Participants with Fragile X Syndrome will be randomized to receive placebo over 4 weeks.	Drug: Placebo; Placebo
Active Comparator: Phase 3: Active comparator; Participants with Fragile X Syndrome will be randomized to receive dose of SPG601 determined from Phase 2b over 12 weeks	Drug: SPG601; synthetic small molecule
Placebo Comparator: Phase 3: Placebo; Participants with Fragile X Syndrome will be randomized to receive placebo for 12 weeks	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	8 weeks
Phase 2b: 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. A higher score indicates better performance	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)	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	8 weeks
Phase 2b: The PK parameters of SPG601 concentrations in plasma-Cmax	Maximum concentration of SPG601 in plasma following dose	4 weeks
Phase 2b: The PK parameters of SPG601 concentrations in plasma-T 1/2	Metabolic half life of SPG601 in plasma following dose	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)	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	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.	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.	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.	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.	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.	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.	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.'	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")	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.	12 weeks
Phase 3: The PK parameters of SPG601 concentrations in plasma-Cmax	Maximum concentration in plasma following administration of SPG601	12 weeks
Phase 3: The PK parameters of SPG601 concentrations in plasma-T 1/2	Metabolic half life of SPG601 in plasma following dose	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.	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	12 weeks

Collaborators and Investigators

• Sponsor: Spinogenix

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: February 18, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Fragile X Syndrome; Fragile X Chromosome; cognitive outcomes
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, Inborn; Neurobehavioral Manifestations; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Intellectual Disability; Genetic Diseases, X-Linked; Sex Chromosome Disorders; Chromosome Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; X-Linked Intellectual Disability; Fragile X Syndrome
• Other Study ID Numbers: SPG601-102 (CLARITY)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No