A Study to Test the Efficacy, Safety, and Tolerability of Bepranemab (UCB0107) in Patients With Mild Cognitive Impairment or Mild Alzheimer's Disease (AD)

Phase 2

Active, not recruiting

Conditions: Alzheimer's Disease

Interventions: Other: Placebo
Biological: Bepranemab

Registration Number: NCT04867616

Lead Sponsor: UCB Biopharma SRL

Brief Summary: The purpose of the study is to investigate the effect of bepranemab versus (vs) placebo on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) up to Week 80 in study participants with prodromal or mild Alzheimer's Disease (AD).

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 466

Inclusion Criteria

50 to 80 years of age
Diagnosis of prodromal/mild cognitive impairment (MCI) due to Alzheimer's Disease (AD) or mild AD according to National Institute of Aging-Alzheimer's Association (NIA-AA)
A global Clinical Dementia Rating (CDR) score of 0.5 to 1.0 and CDR-Memory Box (CDRMB) score ≥0.5 at Screening and Baseline
Score of ≤85 for the delayed recall domain of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at Screening
Mini-Mental State Examination (MMSE) score ≥20 at Screening
Participant has an identified informant that has and will maintain sufficient contact (minimum of 5 hours per week) with the participant to be able to provide accurate information on the participant's cognitive, functional, and emotional states and of the participant's personal care
At least 6 years of formal education after the age of 5 or work experience to exclude mental deficits other than prodromal or mild AD dementia
Evidence of cerebral Aβ accumulation by either positive amyloid assessment by either positron emission tomography (PET) scan or cerebrospinal fluid pTau181/Aβ1-42 ratio assessment

Exclusion Criteria

Any evidence of a condition that may affect cognition other than AD
Contraindications to PET imaging
Inability to tolerate or contraindication to magnetic resonance imaging
Any serious medical condition or abnormality that in the opinion of the investigator would preclude safe participation in and completion of the study or interfere with study assessments and/or study interpretation
Alcohol or drug abuse within 2 years of screening
Use of any experimental therapy within the past 6 months (or 5 half lives) prior to screening
Previous treatment with medication intended to treat a neurodegenerative disorder (other than AD) within 1 year of screening
Chronic daily treatment with atypical antipsychotics, opiates or opioids, benzodiazepines, barbiturates, hypnotics, or any medication with clinically significant centrally acting antihistamine or anticholinergic activitiy
Received treatment with monoclonal antibodies (mAbs), cytokines, immunoglobulins, or other blood products within 3 months or 5 half-lives (whichever is longer) prior to first dosing

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Arm	Placebo	Participants randomized to this arm will receive Placebo to maintain the blinding during the Double-blind Treatment Period and will re-randomized during the Open-label Extension Period to receive pre-specified doses of bepranemab.
Placebo Arm	Bepranemab	Participants randomized to this arm will receive Placebo to maintain the blinding during the Double-blind Treatment Period and will re-randomized during the Open-label Extension Period to receive pre-specified doses of bepranemab.
Dose level 1 bepranemab	Bepranemab	Participants randomized to this arm will receive pre-specified doses (Dose level 1) of bepranemab during the Double-blind Treatment Period and the Open-label Extension Period.
Dose level 2 bepranemab	Bepranemab	Participants randomized to this arm will receive pre-specified doses (Dose level 2) of bepranemab during the Double-blind Treatment Period and the Open-label Extension Period.

Primary Outcome Measures

Name	Time	Method
Change from Baseline to Week 80 in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) total score	From from Baseline to Week 80	The Clinical Dementia Rating (CDR) scale is a clinician-rated dementia staging system that tracks the progression of cognitive impairment in 6 categories (memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care). Each category is scored on a 5-point scale in which None=0, Questionable=0.5, Mild=1, Moderate=2, and Severe=3. The global CDR score is established by clinical scoring rules and has values of 0 (no dementia), 0.5, (questionable dementia), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia). The Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) is obtained by adding the ratings in each of the 6 categories and ranges from 0 to 18 with higher scores indicative of greater impairment.

Secondary Outcome Measures

Name	Time	Method
Change from Baseline to Week 56 and Week 80 on indices of tau burden in the brain as measured by [18F]Genentech tau probe 1 (GTP1) positron emission tomography (PET)	From from Baseline to Week 56 and Week 80	\[18F\]Genentech tau probe 1 (GTP1) positron emission tomography (PET) will be used to assess the brain aggregated tau burden during the study. Images will be transferred to and analyzed by a central imaging laboratory. \[18F\]GTP1 imaging data will be analyzed to determine the standardized uptake value ratio relative to cerebellum in multiple brain regions.
Change from Baseline to Week 56 and Week 80 in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14)	From from Baseline to Week 56 and Week 80	The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) is a composite scale (neuropsychological test battery and clinician reported outcome) that evaluates memory, orientation, attention, reasoning, language, and constructional praxis. Higher scores indicate greater impairment, with a minimum of 0 and a maximum of 90.
Change from Baseline to Week 56 and Week 80 in Amsterdam-Instrumental Activities of Daily Living (A-iADL)	From from Baseline to Week 56 and Week 80	The Amsterdam-Instrumental Activities of Daily Living Questionnaire (A-iADL) is an adaptive and computerized observer-reported outcome measure designed to assess impairments in instrumental activities of daily living (iADL) in early dementia. The questionnaire is administered to an informant such as a relative or friend, with every effort made to use the same informant for a particular study participant throughout the study. The questionnaire consists of 70 items in 7 categories, which takes approximately 20 to 25 minutes to complete. The A-iADL assesses impairments in a broad range of daily activities including household activities, household appliances, finances, work, computer, appliances, leisure activities. The scoring range is 20 to 80 using an item response theory algorithm, with higher scores indicating better functioning (Sikkes et al, 2013).
Incidence of treatment-emergent adverse events (TEAEs)	From Baseline to the Safety Follow-Up (Week 152)	An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study medication.
Incidence of treatment-emergent serious adverse events (TESAEs)	From Baseline to the Safety Follow-Up (Week 152)	A serious adverse event (SAE) is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires inpatient hospitalisation or prolongation of existing hospitalisation * Results in persistent or significant disability/incapacity, or * Is a congenital anomaly/birth defect * Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above
Change from Baseline to Week 56 and Week 80 in Mini-Mental State Examination (MMSE) total score	From from Baseline to Week 56 and Week 80	The MMSE is an 11-item neuropsychological test that is used to assess cognitive status in adults, and can be used to screen for cognitive impairment and to estimate severity of cognitive impairment. It assesses orientation, memory, attention, ability to name, ability to follow verbal and written commands, ability to write a sentence and to copy a drawing. The test takes approximately 10 to 15 minutes to complete. The score ranges from 0 to 30. Lower scores are indicative of poorer cognitive performance.
Incidence of TEAEs leading to discontinuation or death	From Baseline to the Safety Follow-Up (Week 152)	An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study medication.tion, whether or not considered related to the study medication. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study medication.
Incidence of Drug-related TEAEs	From Baseline to the Safety Follow-Up (Week 152)	An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study medication.
Change from Baseline in suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)	From from Baseline to Week 80	The Columbia Suicide Severity Rating Scale (C-SSRS) is a measure used to identify and assess individuals at risk for suicide. The C-SSRS is made up of ten categories, all of which maintain binary responses (yes/no) to indicate a presence or absence of the behavior. The ten categories included in the C-SSRS are as follows: Category 1 - Wish to be Dead; Category 2 - Non-specific Active Suicidal Thoughts; Category 3 - Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Category 4 - Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Category 5 - Active Suicidal Ideation with Specific Plan and Intent; Category 6 - Preparatory Acts or Behavior; Category 7 - Aborted Attempt; Category 8 - Interrupted Attempt; Category 9 - Actual Attempt (non-fatal); Category 10 - Completed Suicide.
Serum concentrations of bepranemab over the 80-week Double-blind Treatment Period	From from Baseline to Week 80	Serum samples will be collected for the measurement of concentrations of bepranemab at different time points during the Double-blind Treatment Period.

Trial Locations

Locations (103): Ah0003 40774
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Katowice, Poland
Ah0003 50428
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Fresno, California, United States
Ah0003 50431
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Fullerton, California, United States
Ah0003 50442
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Irvine, California, United States
Ah0003 50458
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Long Beach, California, United States
Ah0003 50450
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Palo Alto, California, United States
Ah0003 50452
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Pasadena, California, United States
Ah0003 50447
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San Diego, California, United States
Ah0003 50434
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Santa Ana, California, United States
Ah0003 50422
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New Haven, Connecticut, United States
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Ah0003 40774
🇵🇱Katowice, Poland