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

Alzheimer's Disease Clinical Trial

Official title:

A Patient- and Investigator-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Bepranemab (UCB0107) in Study Participants With Prodromal to Mild Alzheimer's Disease (AD), Followed by an Open-Label Extension Period

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04867616
• Other study ID #: AH0003
• Secondary ID: 2020-005829-88
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 9, 2021
• Est. completion date: July 28, 2025

Study information

• Verified date: April 2024
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 421
• Est. completion date: July 28, 2025
• Est. primary completion date: May 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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 Aß accumulation by either positive amyloid assessment by either positron emission tomography (PET) scan or cerebrospinal fluid pTau181/Aß1-42 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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Other:
• Placebo
Pharmaceutical form: Solution for infusion Route of administration: Intravenous infusion Participants will receive Placebo during the Double-blind Treatment Period.

Biological:
• Bepranemab
Pharmaceutical form: Solution for infusion Route of administration: Intravenous infusion Participants will receive pre-specified doses of bepranemab during the Double-blind Treatment Period and the Open-label Extension Period.

Locations

Country	Name	City	State
Belgium	Ah0003 40123	Brussels
Belgium	Ah0003 40575	Brussels
Belgium	Ah0003 40576	Kortrijk
Belgium	Ah0003 40002	Leuven
Canada	Ah0003 50463	Kelowna
Canada	Ah0003 50461	Ottawa
Canada	Ah0003 50520	QC
Canada	Ah0003 50045	Toronto
Canada	Ah0003 50291	Toronto
Canada	Ah0003 50462	Toronto
Canada	Ah0003 50522	West Vancouver
France	Ah0003 40129	Bordeaux
France	Ah0003 40580	Bron Cedex
France	Ah0003 40493	Marseille
France	Ah0003 40635	Nantes
France	Ah0003 40578	Paris
France	Ah0003 40201	Rennes
France	Ah0003 40581	Toulouse
France	Ah0003 40579	Villeurbanne
Germany	Ah0003 40028	Berlin
Germany	Ah0003 40430	Munich
Italy	Ah0003 40371	Monza
Italy	Ah0003 40600	Parma
Italy	Ah0003 40597	Pavia
Italy	Ah0003 40438	Roma
Italy	Ah0003 40596	Rome
Italy	Ah0003 40598	Rome
Netherlands	Ah0003 40450	Amsterdam
Netherlands	Ah0003 40449	Den Bosch
Netherlands	Ah0003 40601	Zwolle
Poland	Ah0003 40603	Bialystok
Poland	Ah0003 40606	Bydgoszcz
Poland	Ah0003 40605	Katowice
Poland	Ah0003 40609	Katowice
Poland	Ah0003 40638	Scinawa
Poland	Ah0003 40608	Szczecin
Poland	Ah0003 40604	Warsaw
Poland	Ah0003 40607	Warsaw
Poland	Ah0003 40602	Warszawa
Poland	Ah0003 40611	Wroclaw
Spain	Ah0003 40159	Barcelona
Spain	Ah0003 40160	Barcelona
Spain	Ah0003 40267	Barcelona
Spain	Ah0003 40612	Barcelona
Spain	Ah0003 40105	Cordoba
Spain	Ah0003 40614	Donostia
Spain	Ah0003 40540	Madrid
Spain	Ah0003 40615	Madrid
Spain	Ah0003 40352	Pamplona
Spain	Ah0003 40280	Sant Cugat Del Valles
Spain	Ah0003 40049	Sevilla
Spain	Ah0003 40453	Terrassa
Spain	Ah0003 40230	Valencia
Spain	Ah0003 40613	Valencia
Spain	Ah0003 40616	Zaragoza
United Kingdom	Ah0003 40662	Birmingham
United Kingdom	Ah0003 40619	Bristol
United Kingdom	Ah0003 40622	Guildford
United Kingdom	Ah0003 40618	London
United Kingdom	Ah0003 40621	London
United Kingdom	Ah0003 40623	Plymouth
United Kingdom	Ah0003 40691	Winchester
United States	Ah0003 50465	Atlantis	Florida
United States	Ah0003 50449	Aventura	Florida
United States	Ah0003 50440	Bellevue	Washington
United States	Ah0003 50435	Boca Raton	Florida
United States	Ah0003 50445	Braintree	Massachusetts
United States	Ah0003 50451	Cincinnati	Ohio
United States	Ah0003 50455	Cordova	Tennessee
United States	Ah0003 50479	Decatur	Georgia
United States	Ah0003 50430	Delray Beach	Florida
United States	Ah0003 50423	East Providence	Rhode Island
United States	Ah0003 50424	Fairfax	Virginia
United States	Ah0003 50429	Fort Myers	Florida
United States	Ah0003 50428	Fresno	California
United States	Ah0003 50431	Fullerton	California
United States	Ah0003 50436	Hialeah	Florida
United States	Ah0003 50380	Houston	Texas
United States	Ah0003 50442	Irvine	California
United States	Ah0003 50458	Long Beach	California
United States	Ah0003 50426	Maitland	Florida
United States	Ah0003 50427	Miami	Florida
United States	Ah0003 50478	Naples	Florida
United States	Ah0003 50420	Neptune	New Jersey
United States	Ah0003 50422	New Haven	Connecticut
United States	Ah0003 50467	New Haven	Connecticut
United States	Ah0003 50453	Newton	Massachusetts
United States	Ah0003 50432	Norfolk	Virginia
United States	Ah0003 50464	Ocoee	Florida
United States	Ah0003 50450	Palo Alto	California
United States	Ah0003 50452	Pasadena	California
United States	Ah0003 50438	Pensacola	Florida
United States	Ah0003 50623	Pensacola	Florida
United States	Ah0003 50457	Port Orange	Florida
United States	Ah0003 50448	Saint Paul	Minnesota
United States	Ah0003 50447	San Diego	California
United States	Ah0003 50434	Santa Ana	California
United States	Ah0003 50421	Stamford	Connecticut
United States	Ah0003 50454	Tampa	Florida
United States	Ah0003 50444	West Palm Beach	Florida
United States	Ah0003 50476	West Palm Beach	Florida
United States	Ah0003 50446	Westchester	Florida

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma SRL

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline to Week 80 in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) total score	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.	From from Baseline to Week 80
Secondary	Incidence of treatment-emergent adverse events (TEAEs)	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.	From Baseline to the Safety Follow-Up (Week 152)
Secondary	Incidence of treatment-emergent serious adverse events (TESAEs)	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	From Baseline to the Safety Follow-Up (Week 152)
Secondary	Incidence of TEAEs leading to discontinuation or death	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.	From Baseline to the Safety Follow-Up (Week 152)
Secondary	Incidence of Drug-related TEAEs	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.	From Baseline to the Safety Follow-Up (Week 152)
Secondary	Change from Baseline in suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)	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.	From from Baseline to Week 80
Secondary	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)	[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.	From from Baseline to Week 56 and Week 80
Secondary	Change from Baseline to Week 56 and Week 80 in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14)	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.	From from Baseline to Week 56 and Week 80
Secondary	Change from Baseline to Week 56 and Week 80 in Amsterdam-Instrumental Activities of Daily Living (A-iADL)	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).	From from Baseline to Week 56 and Week 80
Secondary	Change from Baseline to Week 56 and Week 80 in Mini-Mental State Examination (MMSE) total score	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.	From from Baseline to Week 56 and Week 80
Secondary	Serum concentrations of bepranemab over the 80-week Double-blind Treatment Period	Serum samples will be collected for the measurement of concentrations of bepranemab at different time points during the Double-blind Treatment Period.	From from Baseline to Week 80