Safety, Tolerability, and Preliminary Effectiveness of CTH120 in Fragile X Syndrome

Evaluation of the Safety, Tolerability, and Effectiveness of CTH120 in Adult Males With Fragile X Syndrome

The purpose of this Phase IIa study is to evaluate the safety, tolerability, and effectiveness of CTH120 in adult males with Fragile X syndrome.

A total of 30 randomized adult participants with Fragile X syndrome will participate in the clinical trial (randomization ratio 1:1 treated vs placebo arms). The expected distribution between sites will be 1:1.

This trial will consist of a Screening period of up to 28 days prior to treatment period. A final follow-up period for safety of 14 days (± 2 days) is planned after the end of treatment. The duration of the study will be approximately 3 months for each participant.

Inclusion Criteria:

1. Adult male participants.
2. Aged ≥ 18 and ≤ 45 years.
3. Weight ≥ 50 kg and ≤ 100 kg.
4. Body mass index (BMI) ≥ 18.5 and ≤ 32.
5. Clinical and molecular diagnosis of Fragile X syndrome (> 200 CGG repeats in the promoter region of the FMR1 gene).
6. Participants must have a parent, or other reliable caregiver, who agrees to accompany the participant to all study visits, provide information about the participant as required by the protocol, and ensure compliance with study tests.
7. Legal representative understands and accepts the study procedures. If only one parent signs, he/she should confirm that the other parent does not object to the patient's participation in the study.
8. Participant assenting and/or willing to participate.
9. Signed informed consent by legal representative prior to any study-mandated procedure.
10. Participant with a CGI-S score ≥ 3 evaluated by a clinician with experience on Fragile X syndrome, independently mobile and having sufficient vision and hearing to participate in study evaluations. They must be able to be understood most of the time and must not depend upon other forms of communication, signs, symbol boards or devices as their primary form of communication.
11. Participants are expected to complete all procedures scheduled during the study visits.
12. VCI scaled score >4 on the WISC-V, based on mental age.

Exclusion Criteria:

1. Personal history of infantile spasms/convulsions/epilepsy, severe head trauma or CNS infections (e.g. meningitis), except for infantile febrile seizures.
2. Participants with a current diagnosis of severe (Level 3) autism spectrum disorder or any primary psychiatric diagnosis according to DSM-5 (Diagnostic and Statistical Manual of Mental Disorders-DSM-5). Diagnoses that are secondary, such as attention deficit hyperactivity disorder, depressive disorders, anxiety disorders and conduct disorders are allowed if they are considered to not interfere with study conduct and are stable during the 8 weeks prior to screening. Related allowed treatments must be on stable dosing for the last 3 months.
3. Substance use disorder according to the DSM-5 criteria.
4. Epileptiform abnormalities on EEG (excluding isolated sharp waves and beyond those expected for age).
5. Any life-threatening medical disease.
6. Any other clinically relevant concomitant disease or condition or finding at screening that in the judgment of the investigator could interfere with the treatment, the conduct of the study and related procedures and/or might bias the study results interpretation or could jeopardize the participant's safety.
7. Any clinically significant findings on physical examination including clinically significant vital sign abnormalities, from the perspective of the investigator.
8. Any clinically significant laboratory or ECG abnormalities, from the perspective of the investigator, at Screening and/or prior to the initiation of the study medication.
9. Known hypersensitivity or intolerance to any component of the investigational medicinal product or its excipients.
10. Neuroleptic or antidepressant (SSRI) drugs within the 8 weeks prior to screening, except for sertraline at maximum 100 mg/day, and with no changes in the 8 weeks prior the initiation of the study.
11. More than 3 psychotropic medications simultaneously in the 8 weeks prior to Screening and also during the study.
12. Any new prescription or over the counter drug (except occasional use of paracetamol) in the last 2 weeks before Day 1.
13. Participation in a clinical study with investigational treatments in the last 8 weeks prior to screening.
14. Auditory or visual impairments that cannot be corrected.
15. Positive EtG/EtS test in urine.
16. Positive drug test in urine.