A study to learn if bepranemab is safe and works in people with early stages of Alzheimer’s Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UCB Biopharma

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

18 Oct 2021 → 2 Aug 2025

Decision date (initial)

2024-02-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

UCB Biopharma SRL

External identifiers

EU CT number

2023-506170-12-00

EudraCT number

2020-005829-88

WHO UTN

U1111-1293-3985

ClinicalTrials.gov

NCT04867616

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Others, Pharmacogenomic, Safety, Efficacy, Pharmacodynamic, Pharmacokinetic, Pharmacogenetic

Investigation of 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)

Secondary objectives 1

1. -Evaluation of the safety and tolerability of bepranemab vs. placebo over 80 weeks in study participants with prodromal or mild Alzheimer’s Disease (AD) -Investigation of the effect of bepranemab on tau burden in the brain as measured by [18F]Genentech tau probe 1 (GTP1) positron emission tomography (PET) imaging in study participants with prodromal or mild AD -Investigation of the effect of bepranemab vs placebo on cognitive and functional measures over time in study participants with prodromal or mild AD -Characterisation of the pharmacokinetic (PK) of bepranemab following repeated intravenous (iv) administration in study participants with prodromal or mild AD

Conditions and MedDRA coding

Alzheimer’s Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. - 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 1

1. - 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline to Week 80 in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) total score

Secondary endpoints 10

1. Incidence of treatment-emergent adverse events (TEAEs)
2. Incidence of treatment-emergent serious adverse events (TESAEs)
3. Incidence of TEAEs leading to discontinuation or death
4. Incidence of Drug-related TEAEs
5. Change from Baseline in suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
6. 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)
7. Change from Baseline to Week 56 and Week 80 in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14)
8. Change from Baseline to Week 56 and Week 80 in Amsterdam-Instrumental Activities of Daily Living (AiADL)
9. Change from Baseline to Week 56 and Week 80 in Mini-Mental State Examination (MMSE) total score
10. Serum concentrations of bepranemab over the 80- week Double-blind Treatment Period

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UCB Biopharma

Sponsor organisation

UCB Biopharma

Address

Researchdreef 60

City

Anderlecht

Postcode

1070

Country

Belgium

Scientific contact point

Organisation

UCB Biopharma

Contact name

UCB Cares

Public contact point

Organisation

UCB Biopharma

Contact name

UCB Cares

Third parties 10

Locations

7 EU/EEA countries · 40 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 38 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications