Evaluation of the safety, tolerability, and effectiveness of CTH120 in adult males with Fragile X syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Connecta Therapeutics S.L.

Participant type

Patients

Age range

18-64 years

Gender

Male

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

21 May 2026 → ongoing

Decision date (initial)

2025-12-01

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Spanish Ministry of Science, Innovation and Universities, call 2022 "Colaboración Público-Privada"

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

To assess the safety and tolerability of CTH120 in Fragile X syndrome patients compared to placebo.

Secondary objectives 2

1. To assess the pharmacokinetics of CTH120 and its main metabolite in Fragile X Syndrome patients compared to placebo
2. Preliminary assessment of efficacy of CTH120 in Fragile X syndrome patients compared to placebo

Conditions and MedDRA coding

Fragile X Syndrome

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

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 16

1. Personal history of infantile spasms/convulsions/epilepsy, severe head trauma or CNS infections (e.g. meningitis), except for infantile febrile seizures
2. More than 3 psychotropic medications simultaneously in the 8 weeks prior to screening and also during the study.
3. Any new prescription or over the counter drug (except occasional use of paracetamol) in the last 2 weeks before Day 1
4. Participation in a clinical study with investigational treatments in the last 8 weeks prior to screening
5. Auditory or visual impairments that cannot be corrected
6. Positive EtG/EtS test in urine
7. Positive drug test in urine
8. 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
9. Substance use disorder according to the DSM-5 criteria
10. Epileptiform abnormalities on EEG (excluding isolated sharp waves and beyond those expected for age)
11. Any life-threatening medical disease
12. 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
13. Any clinically significant findings on physical examination including clinically significant vital sign abnormalities, from the perspective of the investigator
14. 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
15. 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
16. Known hypersensitivity or intolerance to any component of the investigational medicinal product or its excipients.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Treatment-emergent adverse events (TEAEs) from Day 1 to the End-of-study (EOS)
2. Treatment-emergent potentially clinically significant abnormalities (PSCAs) in vital signs, 12-lead ECG and safety laboratory parameters from Day 1 to EOS

Secondary endpoints 19

1. Exploratory plasma pharmacokinetics of CTH120 (Cmax, Ctrough, Clast, tmax, tlag, tlast, AUC0-t, AUC0-∞, AUCextrap %, λz, t1/2, CL/F, Vz/F, RAC AUC0-t and RAC Cmax)
2. Exploratory plasma pharmacokinetics of metabolite M4 (Cmax, Ctrough, Clast, tmax, tlag, tlast, AUC0-t, AUC0-∞, AUCextrap %, λz, t1/2, MR Cmax, MR AUC0-t, and MR AUC0-∞, RAC AUC0-t and RAC Cmax)
3. Exploratory PK values assessment considering the different CYP2D6 metaboliser phenotypes
4. Global functioning using the Visual Analogue Scale (VAS)
5. Global severity and improvement using the Clinical Global Impression Improvement Scale (CGI-S and CGI- I)
6. Behaviour troubles using the Aberrant Behaviour Checklist-Community in FXS (ABC-CFXS)
7. Cognitive functioning using the NIH-TCB-ID
8. Anxiety using the Anxiety, Depression, and Mood Scale (ADAMS)
9. Adaptive functioning using the Vineland Adaptive Behaviour Scale (VABS-3)
10. Cognitive functioning using the PedsQL 3.0 Cognitive Functioning Scale (PARENT Reports for Young Adults (ages 18-25) and Adults (ages over 26)
11. Quality of life using the PedsQL 4.0 Generic Core Scales (PARENT Reports for Young Adults (ages 18-25) and Adults (ages over 26)
12. Quality of life using the PedsQL 2.0 Family Impact Module (parent impact for all ages)
13. Quality of sleep using the Pittsburgh sleep quality index (PSQI)
14. Neural functioning using Electroencephalography (EEG) (auditory oddball, resting-state and auditory steady-state response)
15. Social attention using eye-tracking
16. Biorhythm characteristics using Actigraphy
17. Protein levels of FMRP in peripheral blood
18. BDNF concentrations in plasma
19. miRNA profile in plasma (Tertiary endpoint)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Connecta Therapeutics S.L.

Sponsor organisation

Connecta Therapeutics S.L.

Address

Calle Baldiri Reixac 10-12, Poligono Industrial Parc Cientific De Barcelona Poligono Industrial Parc Cientific De Barcelona

City

Barcelona

Postcode

08028

Country

Spain

Scientific contact point

Organisation

Connecta Therapeutics S.L.

Contact name

Josep Prous

Public contact point

Organisation

Connecta Therapeutics S.L.

Contact name

Jordi Fàbrega

Third parties 7

Sponsor responsibilities

Article 77 compliance

Connecta Therapeutics S.L.

Contact point sponsor

Connecta Therapeutics S.L.

Article 77 implementation

Connecta Therapeutics S.L.

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications