A Study to Test the Efficacy, Safety, and Tolerability of Bepranemab (UCB0107) in Patients With Mild Cognitive Impairment or Mild Alzheimer's Disease (AD)
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| ClinicalTrials.gov Identifier: NCT04867616 |
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Recruitment Status :
Active, not recruiting
First Posted : April 30, 2021
Last Update Posted : February 17, 2023
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Sponsor:
UCB Biopharma SRL
Information provided by (Responsible Party):
UCB Pharma ( UCB Biopharma SRL )
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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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 421 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. |
| 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 : | June 9, 2021 |
| Estimated Primary Completion Date : | May 6, 2024 |
| Estimated Study Completion Date : | July 28, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Alzheimer disease
| Arm | Intervention/treatment |
|---|---|
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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.
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Biological: Bepranemab
Participants will receive pre-specified doses of bepranemab during the Double-blind Treatment Period and the Open-label Extension Period. |
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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.
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Biological: Bepranemab
Participants will receive pre-specified doses of bepranemab during the Double-blind Treatment Period and the Open-label Extension Period. |
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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.
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Other: Placebo
Participants will receive Placebo during the Double-blind Treatment Period. Biological: Bepranemab
Participants will receive pre-specified doses of bepranemab during the Double-blind Treatment Period and the Open-label Extension Period. |
Primary Outcome Measures :
- Change from Baseline to Week 80 in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) total score [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
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| Ages Eligible for Study: | 50 Years to 80 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04867616
Locations
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Sponsors and Collaborators
UCB Biopharma SRL
Investigators
| Study Director: | UCB Cares | 001 844 599 2273 (UCB) |
| Responsible Party: | UCB Biopharma SRL |
| ClinicalTrials.gov Identifier: | NCT04867616 |
| Other Study ID Numbers: |
AH0003 2020-005829-88 ( EudraCT Number ) |
| First Posted: | April 30, 2021 Key Record Dates |
| Last Update Posted: | February 17, 2023 |
| Last Verified: | February 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of reidentifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion. |
| Access Criteria: | Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal. |
| URL: | http://www.Vivli.org |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
Keywords provided by UCB Pharma ( UCB Biopharma SRL ):
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Alzheimer's Disease Bepranemab UCB0107 Phase 2 |
Additional relevant MeSH terms:
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Alzheimer Disease Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases |
Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders |