LEVETIRACETAM for Down syndrome | Alzheimer's disease

Inclusion criteria

• {"criterion_text":"- Diagnosed with Down Syndrome (DS), either with a karyotype or a compatible typical phenotype.\n- Symptomatic Alzheimer’s Disease (AD) dementia, based on change in functionality and neuropsychological tests’ results. Different cut-off points will be established to diagnose dementia depending on the level of intellectual disability of the individual, according to previous experience (Benejam et al; 2020): in adults with mild intellectual disability, a CAMCOG-DS score of 80 and an mCRT score of 29 will be chosen, whereas values of 56 and 28, respectively, will be used in subjects with moderate intellectual disability. Doubtful cases (e.g., with compromised functionality, but without alteration in the neuropsychological assessment) or those unable to complete the evaluation will be categorized by consensus among expert clinicians, using all available clinical information.\n- Willing and able caregiver who has daily contact with the study subject.\n- Subjects and caregivers must be able to comply with the prescribed regimen of study treatment throughout the course of the study and meet a minimum required time commitment of biannual in-person visits\n- Any concurrent treatment for AD approved by the European Medicines Agency (EMA) must be stable for at least 30 days prior to screening and at least 60 days prior to study day 1. Other medications (except for those listed under exclusion criteria) are allowed as long as the dose is stable for 30 days prior to screening\n- Age over 40 years at time of screening. This age cutoff has been selected because the beginning of cognitive decline attributable to AD in the study population is exceptional below this age\n- Subjects and/or their caregivers must be able to provide their consent before participating in any study-related procedures. A thorough description of the informed consent process can be found under section 12.2. Participants’ Informed Consent Process."}

Exclusion criteria

• {"criterion_text":"- Cognitive changes attributable to causes other than AD (for example, but not limited to, uncorrected visual or hearing deficit, severe, untreated sleep apnea or uncontrolled thyroid disorders).\n- Significant risk of suicide, defined using the C-SSRS as the subject answering “yes” to suicidal ideation questions 4 or 5 or answering “yes” to suicidal behavior within the past 12 months\n- Deviations from normal values for hematologic parameters, liver function tests, and other biochemical measures, judged to be clinically significant by the investigator.\n- Pregnant and breastfeeding patients\n- Participation in another clinical trial within 3 months of screening.\n- Hypersensitivity to the active ingredient, other pyrrolidone derivatives, or any of the excipients\n- Previous history of adult-onset epileptic seizures (over 18 years old).\n- Treatment with any kind of antiepileptic drugs, benzodiazepines, narcotics.\n- Significant comorbidities or analytical abnormalities, such as:\n- Any unstable and/or clinically significant medical condition likely to hamper the evaluation of safety and/or efficacy of the study (eg, moderate and/or severe untreated obstructive sleep apnea, clinically significant reduction in serum B12 or folate levels, clinically significant abnormalities of thyroid function, stroke, or other cerebrovascular conditions), as per investigator’s judgement.\n- Severe renal dysfunction (creatinine clearance < 30 mL/min), which would affect serum levetiracetam levels, or any other medical condition which is determined by the investigators to potentially create an undue risk for an adverse effect\n- Concomitant or past history psychiatric or neurologic disorder other than those considered to be related to AD (eg, head injury with loss of consciousness, symptomatic stroke, Parkinson’s disease, severe carotid occlusive disease, transient ischemic attacks [TIAs])."}

Primary endpoints

• {"endpoint_text":"- Efficacy: Number (percentage) of subjects who do not develop a bilateral tonic-clonic epileptic seizure during the study (96 weeks). Therefore, a non-responder, or treatment failure, is defined as any subject who develops a bilateral tonic-clonic epileptic seizure during the study.","definition_or_measurement_approach":"The presence and characteristics of bilateral tonic-clonic seizures will be recorded during the medical visit."}

Secondary endpoints

• {"endpoint_text":"- Time to first bilateral tonic-clonic epileptic seizure (days)","definition_or_measurement_approach":""}
• {"endpoint_text":"- All-cause mortality: - Number (percentage) of patients dying from any cause during the study. - Number (percentage) of patients dying due to AD complications during the study. - Time to death (days).","definition_or_measurement_approach":""}
• {"endpoint_text":"- AD-related biomarkers: - Cognition: The neuropsychological assessment will include the CAMCOG-DS, mCRT","definition_or_measurement_approach":"Neuropsychological tests CAMCOG-DS and mCRT to assess cognition."}
• {"endpoint_text":"- Plasma biomarkers: plasma concentrations of 217-pTau and NfL (pg/mL).","definition_or_measurement_approach":"Measurement of plasma 217-pTau and NfL concentrations (pg/mL)."}
• {"endpoint_text":"- Neuroimaging biomarkers (MRI): Volumetric measures extracted for 12 subcortical gray matter regions (six left and six right, including the amygdala, caudate nucleus accumbens, pallidum, putamen, and thalamus), the left and right hippocampi, and the left and right lateral ventricles. Cortical thickness measure extracted for 34 left-hemispheric gray matter regions, and 34 right hemispheric gray matter regions (Whelan et al, Brain 2018).","definition_or_measurement_approach":"MRI volumetric and cortical thickness measures as specified."}
• {"endpoint_text":"- Electroencephalography (EEG): Appearance of graphoelements with irritative characteristics: spike-wave, polyspike-wave, acute wave and spike or focal and generalized slowing of the activity, power spectrum analysis and synchronization by bands.","definition_or_measurement_approach":"EEG assessment of epileptiform graphoelements, power spectrum and band synchronization."}
• {"endpoint_text":"- Safety: The primary endpoints are number, type, frequency, and intensity of AEs evaluated until the end of treatment and assessment of tolerability during the medical visit, physical and neurological examination, vital signs, brain MRI assessment, suicidality (as measured with the C-SSRS), routine hematology and biochemistry evaluation in blood.","definition_or_measurement_approach":"Adverse events and safety assessments including medical visit, physical and neurological exams, vital signs, MRI, C-SSRS suicidality scale, routine hematology and biochemistry."}

Spain

Earliest CTIS Part Ii Submission Date

25-04-2025

Latest Decision Or Authorization Date

04-11-2025

Processing Time Days

193

Number Of Sites

5

Number Of Participants

120

Primary sponsor

Full Name

Fundacio Institut De Recerca De L'Hospital De La Santa Creu I Sant Pau

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Spain