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

NCT07654114 | Recruiting Phase 2 DMC

• 2 other identifiers: CTH-CTH120-FXS-012025-522972-97-00
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Fragile X Syndrome (FXS); Fragile X Syndrome

Keywords

Fragile X Syndrome; FXS; Fragile X; Neureodevelopmental Disorders; Central Nervous System Diseases; Intellectual Disability; Neurobehavioral Manifestations; Genetic Diseases, X linked; Congenital Abnormalities; Orphan Diseases; Rare Diseases

Outcome Measures

Primary Outcomes (15)

• Treatment-emergent adverse events (TEAEs).

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. AEs will be described in terms of result, frequency, intensity, medical decision, relation with study drug, as well as treatment received and subject retirement, duration, and time elapsed. AEs will also be listed and coded using the MedDRA Dictionary for the term's codification.

  From Day 1 to End-of-study: EOS will be on Day 56 (±2 days).

• Treatment-emergent potentially clinically significant abnormalities (PSCAs) in blood pressure (mmHg).

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. Blood pressure (mmHg) will be measured in the supine position following a 5 min rest.

  From Day 1 to End-of-study (EOS): on Day 56 (±2 days).

• Treatment-emergent potentially clinically significant abnormalities (PSCAs) in pulse rate (bpm).

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. Pulse rate (bpm) will be measured in the supine position following a 5 min rest.

  From Day 1 to End-of-study (EOS): on Day 56 (±2 days).

• Treatment-emergent potentially clinically significant abnormalities (PSCAs) in body temperature (ºC).

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. Body temperature will be measured using an automated vital sign monitor device.

  From Day 1 to End-of-study (EOS): on Day 56 (±2 days).

• Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: heart rate (bpm).

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. Triplicate 12-lead ECGs will be recorded in a supine position after at least 10-minute rest. Each lead will be recorded for at least 3 beats at a speed of 25 mm/s.CGs will be recorded using a machine that automatically calculates the following parameter: heart rate (bpm).

  From Day 1 to End-of-study (EOS): on Day 56 (±2 days).

• Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: rhythm.

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. Triplicate 12-lead ECGs will be recorded in a supine position after at least 10-minute rest. Each lead will be recorded for at least 3 beats at a speed of 25 mm/s.CGs will be recorded using a machine that automatically calculates the following parameter: rhythm.

  From Day 1 to End-of-study (EOS): on Day 56 (±2 days).

• Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: PQ/PR interval (ms).

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. Triplicate 12-lead ECGs will be recorded in a supine position after at least 10-minute rest. Each lead will be recorded for at least 3 beats at a speed of 25 mm/s. ECGs will be recorded using a machine that automatically calculates the following parameter: PQ/PR interval (ms).

  From Day 1 to End-of-study (EOS): on Day 56 (±2 days).

• Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: QRS duration (ms).

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. Triplicate 12-lead ECGs will be recorded in a supine position after at least 10-minute rest. Each lead will be recorded for at least 3 beats at a speed of 25 mm/s. ECGs will be recorded using a machine that automatically calculates the following parameter: QRS duration (ms).

  From Day 1 to End-of-study (EOS): on Day 56 (±2 days).

• Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: QT (ms).

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. Triplicate 12-lead ECGs will be recorded in a supine position after at least 10-minute rest. Each lead will be recorded for at least 3 beats at a speed of 25 mm/s. ECGs will be recorded using a machine that automatically calculates the following parameter: QT (ms).

  From Day 1 to End-of-study (EOS): on Day 56 (±2 days).

• Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: QTcF (ms).

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. Triplicate 12-lead ECGs will be recorded in a supine position after at least 10-minute rest. Each lead will be recorded for at least 3 beats at a speed of 25 mm/s. ECGs will be recorded using a machine that automatically calculates the following parameter: QTcF (ms).

  From Day 1 to End-of-study (EOS): on Day 56 (±2 days).

• Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: haematology.

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. The following tests will be performed: • Haematology: haemoglobin, haematocrit, red blood cell count, mean corpuscular volume, mean corpuscular haemoglobin, white blood cell count (absolute and %), platelets.

  Screening visit (From Day -28 to Day -1), on Day 15, on Day 28, on Day 42 and Day 56 (± 2 days) (End-of-study (EOS)).

• Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: serum chemistry.

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. The following tests will be performed: • Serum chemistry: sodium, potassium, urea, creatinine, albumin, calcium, phosphate, glucose, total cholesterol, LDL, HDL, TG, ALT, AST, GGT, total bilirubin, CPK, LDH.

  Screening visit (From Day -28 to Day -1), on Day 15, on Day 28, on Day 42 and Day 56 (± 2 days) (End-of-study (EOS)).

• Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: coagulation.

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. The following tests will be performed: • Coagulation parameters: INR, aPTT, PT.

  Screening visit (From Day -28 to Day -1), on Day 15, on Day 28, on Day 42 and Day 56 (± 2 days) (End-of-study (EOS)).

• Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: urinalysis.

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. The following tests will be performed: • Urinalysis parameters: leucocytes, protein, bilirubin, urobilinogen, ketones, red blood cells, pH, nitrite, glucose (only at Screening visit).

  Screening visit (from Day -28 to Day -1).

• Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: viral serology and detection.

  Primary Safety and Tolerability endpoint for FXS-CTH120-01. The following tests will be performed: • Viral serology and detection: Hepatitis B (HBsAg), Hepatitis C (Ac IgG VHC) and HIV antibody.

  Screening visit (from day -28 to Day -1).

Secondary Outcomes (31)

• Observed maximum concentration (Cmax).

  On Day 15 and Day 42.

• Measured concentration at the end of a dosing interval at steady state (Ctrough).

  On Day 15, Day 28 and Day 42.

• Last analytically quantifiable plasma concentration above LLOQ (Clast).

  On Day 15 and Day 42.

• Time to reach Cmax (tmax).

  On Day 15 and Day 42.

• Lag-time (time delay between drug administration and first observed concentration above LOQ in plasma) (tlag).

  On Day 15 and Day 42.

Study Arms (2)

CTH120

EXPERIMENTAL

CTH120 75 mg hard capsules will be provided by CONNECTA Therapeutics, S.L. as hard capsules for oral administration. CTH120 75 mg hard capsules contain 75 mg CTH120 drug substance (dose expressed as active moiety) and compendial excipients to be orally administered after breakfast and after dinner with a glass of water. The recommended dosage of CTH120 is 75 mg orally twice daily (BID) in fed conditions after breakfast and after dinner.

Drug: CTH120

CTH120 placebo hard capsules

PLACEBO COMPARATOR

CTH120 placebo hard capsules will be provided by CONNECTA Therapeutics, S.L. as hard capsules for oral administration. CTH120 matching placebo hard capsules (that contain the same compendial excipients than and are identical in appearance to CTH120 75 mg hard capsules) will be orally administered twice daily (BID) in fed conditions after breakfast and after dinner with a glass of water.

Other: CTH120 placebo hard capsules

Interventions

CTH120 DRUG

15 participants will be randomized to receive CTH120 75 mg hard capsules. Capsules of CTH120 will be administered by the oral route to participants twice a day, one capsule in the morning and one capsule in the evening, at approximately the same times each day, after breakfast (morning dose) and after dinner (evening dose), with a glass of water. The evening dose will be taken approximately 12 h from the morning dose, and preferably before midnight. The evening dose must not be taken before at least 8 hours from the morning dose.

CTH120

CTH120 placebo hard capsules OTHER

15 participants will be randomized to receive CTH120 placebo hard capsules. Capsules of CTH120 matching placebo will be administered by the oral route to participants twice a day, one capsule in the morning and one capsule in the evening, at approximately the same times each day, after breakfast (morning dose) and after dinner (evening dose), with a glass of water. The evening dose will be taken approximately 12 h from the morning dose, and preferably before midnight. The evening dose must not be taken before at least 8 hours from the morning dose.

CTH120 placebo hard capsules

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult male participants.
• Aged ≥ 18 and ≤ 45 years.
• Weight ≥ 50 kg and ≤ 100 kg.
• Body mass index (BMI) ≥ 18.5 and ≤ 32.
• Clinical and molecular diagnosis of Fragile X syndrome (\> 200 CGG repeats in the promoter region of the FMR1 gene).
• 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.
• 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.
• Participant assenting and/or willing to participate.
• Signed informed consent by legal representative prior to any study-mandated procedure.
• 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.
• Participants are expected to complete all procedures scheduled during the study visits.
• VCI scaled score \>4 on the WISC-V, based on mental age.

You may not qualify if:

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

Sponsors & Collaborators

• Connecta Therapeutics, S.L.: lead
• Hospital del Mar Research Institute (IMIM): collaborator
• Corporacion Parc Tauli: collaborator
• Ministry of Science and Innovation, Spain: collaborator
• Astrum CRO, S.L.: collaborator

Study Sites (2)

Hospital del Mar Medical Research Institute

Barcelona, Barcelona, 08003, Spain

RECRUITING

Consorci Corporació Sanitaria Parc Taulí. Institut Investigació i Innovació Parc Taulí (I3PT)

Sabadell, Barcelona, 08208, Spain

RECRUITING

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Related Links

• Clinical Trials - CONNECTA Therapeutics

MeSH Terms

Conditions

Fragile X Syndrome; Central Nervous System Diseases; Intellectual Disability; Neurobehavioral Manifestations; Genetic Diseases, X-Linked; Congenital Abnormalities; Rare Diseases

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders; Disease Attributes; Pathologic Processes

Study Officials

• Rafael De la Torre, Pharm, PhD

  Hospital del Mar Medical Research Institute

  PRINCIPAL INVESTIGATOR

• Ana María Aldea, MD, PhD

  Hospital del Mar Medical Research Institute

  PRINCIPAL INVESTIGATOR

• Ana Roche Martínez, MD, PhD

  Consorci Corporació Sanitària Parc Taulí. Institut d'Investigació i Innovació Parc Taulí (I3PT)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Josep Prous, PhD

CONTACT

(+34) 934034509; clinicaltrials@connectatherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participants, Investigators and designees involved in the conduct of the trial will be blinded to the identity of the trial CTH120 or placebo doses. Thus, all trial stakeholders but the Pharmacy personnel will be blinded throughout this part of the trial including the Sponsor personnel, the participating participants, the study team at the investigational site, including the person administering the study drug as well as the CRO personnel involved in the data management and analyses.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase IIa, randomized, double-blind, placebo-controlled, parallel groups, multicentre clinical trial, to assess safety, tolerability and efficacy of CTH120 75 mg BID and matching placebo in adult males with Fragile X syndrome (aged 18 to 45 years).

Study Record Dates

• First Submitted: June 12, 2026
• First Posted: June 17, 2026
• Study Start: May 21, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: June 17, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2)