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

Sponsor

UCB Biopharma SRL (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04867616

Collaborator

(none)

450

Enrollment

116

Locations

Arms

48.7

Anticipated Duration (Months)

3.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Other: Placebo Biological: Bepranemab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

450 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Upon completion of the 80-week Double-blind Treatment Period, study participants will be eligible to enter a 48-week Open-label Extension Period with planned treatments of bepranemab for 44 weeks, followed by a Safety Follow-up Visit 20 weeks after the last infusion of investigational medicinal product.Upon completion of the 80-week Double-blind Treatment Period, study participants will be eligible to enter a 48-week Open-label Extension Period with planned treatments of bepranemab for 44 weeks, followed by a Safety Follow-up Visit 20 weeks after the last infusion of investigational medicinal product.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 9, 2021

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose level 1 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.	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.
Experimental: Dose level 2 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.	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.
Placebo Comparator: Placebo Arm 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.	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.

Arm

Intervention/Treatment

Experimental: Dose level 1 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.

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.

Experimental: Dose level 2 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.

Biological: Bepranemab

Placebo Comparator: Placebo Arm

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.

Other: Placebo

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

Biological: Bepranemab

Outcome Measures

Primary Outcome Measures

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

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
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.
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).
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ah0003 50305	Sun City	Arizona	United States	85351
2	Ah0003 50428	Fresno	California	United States	93710
3	Ah0003 50431	Fullerton	California	United States	92835
4	Ah0003 50442	Irvine	California	United States	92614
5	Ah0003 50458	Long Beach	California	United States	90807
6	Ah0003 50450	Palo Alto	California	United States	94303
7	Ah0003 50452	Pasadena	California	United States	91105
8	Ah0003 50447	San Diego	California	United States	92123
9	Ah0003 50434	Santa Ana	California	United States	92705
10	Ah0003 50422	New Haven	Connecticut	United States	06510
11	Ah0003 50467	New Haven	Connecticut	United States	06510
12	Ah0003 50421	Stamford	Connecticut	United States	06905
13	Ah0003 50465	Atlantis	Florida	United States	33462
14	Ah0003 50449	Aventura	Florida	United States	33180
15	Ah0003 50435	Boca Raton	Florida	United States	33487
16	Ah0003 50437	Boynton Beach	Florida	United States	33437
17	Ah0003 50430	Delray Beach	Florida	United States	33445
18	Ah0003 50429	Fort Myers	Florida	United States	33912
19	Ah0003 50436	Hialeah	Florida	United States	33016
20	Ah0003 50426	Maitland	Florida	United States	32751
21	Ah0003 50427	Miami	Florida	United States	33125
22	Ah0003 50478	Naples	Florida	United States	34105
23	Ah0003 50464	Ocoee	Florida	United States	34761
24	Ah0003 50438	Pensacola	Florida	United States	32502
25	Ah0003 50457	Port Orange	Florida	United States	32127
26	Ah0003 50454	Tampa	Florida	United States	33613
27	Ah0003 50444	West Palm Beach	Florida	United States	33407
28	Ah0003 50476	West Palm Beach	Florida	United States	33409
29	Ah0003 50446	Westchester	Florida	United States	33155
30	Ah0003 50479	Decatur	Georgia	United States	30033
31	Ah0003 50439	Lexington	Kentucky	United States	40504
32	Ah0003 50445	Braintree	Massachusetts	United States	02184
33	Ah0003 50453	Newton	Massachusetts	United States	02459
34	Ah0003 50448	Saint Paul	Minnesota	United States	55130
35	Ah0003 50420	Neptune	New Jersey	United States	07753
36	Ah0003 50451	Cincinnati	Ohio	United States	45219
37	Ah0003 50255	Columbus	Ohio	United States	43221
38	Ah0003 50443	Portland	Oregon	United States	97210
39	Ah0003 50423	East Providence	Rhode Island	United States	02914
40	Ah0003 50455	Cordova	Tennessee	United States	38018
41	Ah0003 50380	Houston	Texas	United States	77054
42	Ah0003 50424	Fairfax	Virginia	United States	22031
43	Ah0003 50432	Norfolk	Virginia	United States	23507
44	Ah0003 50440	Bellevue	Washington	United States	98007
45	Ah0003 40121	Brussels		Belgium
46	Ah0003 40123	Brussels		Belgium
47	Ah0003 40575	Brussels		Belgium
48	Ah0003 40576	Kortrijk		Belgium
49	Ah0003 40002	Leuven		Belgium
50	Ah0003 50463	Kelowna		Canada
51	Ah0003 50461	Ottawa		Canada
52	Ah0003 50520	Quebec		Canada
53	Ah0003 50045	Toronto		Canada
54	Ah0003 50291	Toronto		Canada
55	Ah0003 50462	Toronto		Canada
56	Ah0003 50522	West Vancouver		Canada
57	Ah0003 40129	Bordeaux		France
58	Ah0003 40580	Bron Cedex		France
59	Ah0003 40636	Dijon Cedex		France
60	Ah0003 40493	Marseille		France
61	Ah0003 40635	Nantes		France
62	Ah0003 40578	Paris		France
63	Ah0003 40201	Rennes		France
64	Ah0003 40131	Strasbourg		France
65	Ah0003 40581	Toulouse		France
66	Ah0003 40579	Villeurbanne		France
67	Ah0003 40590	Berlin		Germany
68	Ah0003 40430	Munich		Germany
69	Ah0003 40592	Siegen		Germany
70	Ah0003 40577	ULM		Germany
71	Ah0003 40371	Monza		Italy
72	Ah0003 40600	Parma		Italy
73	Ah0003 40597	Pavia		Italy
74	Ah0003 40497	Pozzilli		Italy
75	Ah0003 40438	Roma		Italy
76	Ah0003 40596	Rome		Italy
77	Ah0003 40598	Rome		Italy
78	Ah0003 40450	Amsterdam		Netherlands
79	Ah0003 40449	Den Bosch		Netherlands
80	Ah0003 40601	Zwolle		Netherlands
81	Ah0003 40603	Bialystok		Poland
82	Ah0003 40606	Bydgoszcz		Poland
83	Ah0003 40605	Katowice		Poland
84	Ah0003 40609	Katowice		Poland
85	Ah0003 40638	Scinawa		Poland
86	Ah0003 40608	Szczecin		Poland
87	Ah0003 40604	Warsaw		Poland
88	Ah0003 40607	Warsaw		Poland
89	Ah0003 40602	Warszawa		Poland
90	Ah0003 40611	Wroclaw		Poland
91	Ah0003 40159	Barcelona		Spain
92	Ah0003 40160	Barcelona		Spain
93	Ah0003 40267	Barcelona		Spain
94	Ah0003 40612	Barcelona		Spain
95	Ah0003 40105	Cordoba		Spain
96	Ah0003 40614	Donostia		Spain
97	Ah0003 40540	Madrid		Spain
98	Ah0003 40615	Madrid		Spain
99	Ah0003 40352	Pamplona		Spain
100	Ah0003 40280	Sant Cugat Del Valles		Spain
101	Ah0003 40617	Santander		Spain
102	Ah0003 40049	Sevilla		Spain
103	Ah0003 40453	Terrassa		Spain
104	Ah0003 40230	Valencia		Spain
105	Ah0003 40613	Valencia		Spain
106	Ah0003 40616	Zaragoza		Spain
107	Ah0003 40662	Birmingham		United Kingdom
108	Ah0003 40619	Bristol		United Kingdom
109	Ah0003 40639	Glasgow		United Kingdom
110	Ah0003 40622	Guildford		United Kingdom
111	Ah0003 40618	London		United Kingdom
112	Ah0003 40621	London		United Kingdom
113	Ah0003 40620	Motherwell		United Kingdom
114	Ah0003 40623	Plymouth		United Kingdom
115	Ah0003 40391	Southampton		United Kingdom
116	Ah0003 40691	Winchester		United Kingdom

Sponsors and Collaborators

UCB Biopharma SRL

Investigators

Study Director: UCB Cares, 001 844 599 2273 (UCB)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

UCB Biopharma SRL

ClinicalTrials.gov Identifier:

NCT04867616

Other Study ID Numbers:

AH0003
2020-005829-88

First Posted:

Apr 30, 2021

Last Update Posted:

Aug 19, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by UCB Biopharma SRL

Additional relevant MeSH terms:

Alzheimer Disease

Study Results

No Results Posted as of Aug 19, 2022