A Study to Assess Safety of ABBV-916 and How Intravenous ABBV-916 Moves Through Body and Affects Brain Amyloid Plaque Clearance in Adult Participants (Aged 50-90 Years) With Early Alzheimer's Disease

• ClinicalTrials.gov Identifier: NCT05291234
• Recruitment Status: Recruiting
• First Posted: March 22, 2022
• Last Update Posted: April 8, 2024
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: March 21, 2022
• First Posted Date: March 22, 2022
• Last Update Posted Date: April 8, 2024
• Actual Study Start Date: August 15, 2022
• Estimated Primary Completion Date: March 26, 2031 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 15, 2024)

• Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to approximately 160 weeks ]
  An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study.
• Stage A: Maximum Observed Serum Concentration (Cmax) for Multiple Ascending Dose of ABBV-916 [ Time Frame: Up to approximately 24 weeks ]
  Cmax of ABBV-916 will be determined.
• Stage A: Time to Cmax (Tmax) for Multiple Ascending Dose of ABBV-916 [ Time Frame: Up to approximately 24 weeks ]
  Tmax of ABBV-916 will be determined.
• Stage A: Apparent Terminal Phase Elimination Rate Constant (β) of ABBV-916 [ Time Frame: Up to approximately 24 weeks ]
  Apparent terminal phase elimination rate constant (β) of ABBV-916 will be determined.
• Stage A: Terminal Phase Elimination Half-Life (t1/2) of ABBV-916 [ Time Frame: Up to approximately 24 weeks ]
  T1/2 of ABBV-916 will be determined.
• Stage A: Trough Serum Concentration (Ctrough) of ABBV-916 at the End of a Dosing Interval [ Time Frame: Up to approximately 24 weeks ]
  Ctrough of ABBV-916 will be determined.
• Stage A: Area Under the Concentration-Time Curve (AUC) of ABBV-916 [ Time Frame: Up to approximately 24 weeks ]
  AUC of ABBV-916 will be determined.
• Stage A: Cerebrospinal Fluid (CSF) Concentration as a Measure of ABBV-916 Crossing the Blood Brain Barrier [ Time Frame: Up to approximately 24 weeks ]
  The central value for ratio of ABBV-916 concentration in cerebrospinal fluid (CSF) to that in serum will be estimated for evaluation of the fraction of ABBV-916 crossing the blood brain barrier.
• Stage A: Percentage of Participants With Antidrug Antibodies (ADA) as a Measure of Immunogenicity Following Multiple Ascending Dose of ABBV-916 [ Time Frame: Up to approximately 24 weeks ]
  Antidrug antibody (ADA) classification and titers for positive ADA samples will be determined.
• Stage B: Change in Brain Amyloid Plaque Deposition (Amyloid Centiloid Value) [ Time Frame: Baseline (Week 0) through Week 24 ]
  Change from baseline in brain amyloid plaque deposition (amyloid centiloid value) is measured by amyloid positron emission tomography (PET) scan.

Original Primary Outcome Measures (submitted: March 21, 2022)

• Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to approximately 160 weeks ]
  An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study.
• Stage A: Maximum Observed Serum Concentration (Cmax) for Multiple Ascending Dose of ABBV-916 [ Time Frame: Up to approximately 24 weeks ]
  Cmax of ABBV-916 will be determined.
• Stage A: Time to Cmax (Tmax) for Multiple Ascending Dose of ABBV-916 [ Time Frame: Up to approximately 24 weeks ]
  Tmax of ABBV-916 will be determined.
• Stage A: Apparent Terminal Phase Elimination Rate Constant (β) of ABBV-916 [ Time Frame: Up to approximately 24 weeks ]
  Apparent terminal phase elimination rate constant (β) of ABBV-916 will be determined.
• Stage A: Terminal Phase Elimination Half-Life (t1/2) of ABBV-916 [ Time Frame: Up to approximately 24 weeks ]
  T1/2 of ABBV-916 will be determined.
• Stage A: Trough Serum Concentration (Ctrough) of ABBV-916 at the End of a Dosing Interval [ Time Frame: Up to approximately 24 weeks ]
  Ctrough of ABBV-916 will be determined.
• Stage A: Area Under the Concentration-Time Curve (AUC) of ABBV-916 [ Time Frame: Up to approximately 24 weeks ]
  AUC of ABBV-916 will be determined.
• Stage A: Clearance (CL) of ABBV-916 [ Time Frame: Up to approximately 24 weeks ]
  Clearance (CL) of ABBV-916 will be determined.
• Stage A: Cerebrospinal Fluid (CSF) Concentration as a Measure of ABBV-916 Crossing the Blood Brain Barrier [ Time Frame: Up to approximately 24 weeks ]
  The central value for ratio of ABBV-916 concentration in cerebrospinal fluid (CSF) to that in serum will be estimated for evaluation of the fraction of ABBV-916 crossing the blood brain barrier.
• Stage A: Percentage of Participants With Antidrug Antibodies (ADA) as a Measure of Immunogenicity Following Multiple Ascending Dose of ABBV-916 [ Time Frame: Up to approximately 24 weeks ]
  Antidrug antibody (ADA) classification and titers for positive ADA samples will be determined.
• Stage B: Change in Brain Amyloid Plaque Deposition (Amyloid Centiloid Value) [ Time Frame: Baseline (Week 0) through Week 24 ]
  Change from baseline in brain amyloid plaque deposition (amyloid centiloid value) is measured by amyloid positron emission tomography (PET) scan.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Assess Safety of ABBV-916 and How Intravenous ABBV-916 Moves Through Body and Affects Brain Amyloid Plaque Clearance in Adult Participants (Aged 50-90 Years) With Early Alzheimer's Disease
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of ABBV-916 in Subjects With Early Alzheimer's Disease

Brief Summary

Alzheimer's disease (AD) is a progressive, irreversible neurological disorder and is the most common cause of dementia in the elderly population. Clinical symptoms of the disease may begin with occasional forgetfulness such as misplacement of items, forgetting important dates or events, and may progress to noticeable memory loss, increased confusion and agitation, and eventually, loss of independence and non-responsiveness. This study will assess how safe and effective ABBV-916 is in treating early AD. Adverse events, change in disease activity, and how ABBV-916 moves through body of participants will be assessed.

ABBV-916 is an investigational drug being developed for the treatment of early AD. This study is conducted in 2 stages. Stage A is a multiple ascending dose study. There is a 1 in 4 chance that participants are assigned to receive placebo. Stage B is a proof-of-concept study. In Stage B, there is a 1 in 5 chance that participants will be assigned to receive placebo. The first 6 months of this study are "double-blind," which means that neither the trial participant nor the study doctors know which treatments will be given. This will be followed by a 2-year extension period in which all participants will receive ABBV-916. Approximately 195 participants aged 50-90 years will be enrolled in about 90 sites across the world.

Participants will receive intravenous (IV) doses of ABBV-916 or placebo once every 4 weeks (Q4W) for 24 weeks and will be followed for an additional 16 weeks. Participants will have the option of participating in a 2-year, open-label, Extension Period receiving IV ABBV-916.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, magnetic resonance imaging (MRI), blood tests, checking for side effects and completing questionnaires.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alzheimer's Disease (AD)

Intervention

• Drug: ABBV-916
  Intravenous administration
• Drug: Placebo
  Intravenous administration

Study Arms

• Experimental: Stage A: ABBV-916
  Participants will receive ABBV-916 for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.
  Intervention: Drug: ABBV-916
• Placebo Comparator: Stage A: Placebo for ABBV-916
  Participants will receive Placebo for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.
  Intervention: Drug: Placebo
• Experimental: Stage B: ABBV-916 Dose A
  Participants will receive ABBV-916 Dose A for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.
  Intervention: Drug: ABBV-916
• Placebo Comparator: Stage B: Placebo for ABBV-916
  Participants will receive Placebo for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.
  Intervention: Drug: Placebo
• Experimental: Stage B: ABBV-916 Dose B
  Participants will receive ABBV-916 Dose B for 24 weeks. Participants at the end of 24 weeks will have the option of participating in the 2-year Extension Period.
  Intervention: Drug: ABBV-916

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 8, 2022): 195
• Original Estimated Enrollment (submitted: March 21, 2022): 288
• Estimated Study Completion Date: March 26, 2031
• Estimated Primary Completion Date: March 26, 2031 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of Stage 3 or Stage 4 Alzheimer's disease (AD) based on the 2018 National Institute on Aging (NIA)-Alzheimer's Association (AA) Research Framework Criteria.

  • Mini-Mental State Examination (MMSE) score of 20 to 28, inclusive, at Screening.
  • Blood-based biomarker results with a value consistent with amyloid positron emission tomography (PET) positivity. The biomarker will be chosen by the sponsor and described in the Laboratory Manual. Biomarker results will not be required for eligibility if the participant has a positive Amyloid PET scan meeting the central reader criteria.
• Amyloid PET scan results consistent with amyloid pathology.
• Stage B: Participants must have a study partner who spends a minimum average of 10 hours per week with the participant.

Exclusion Criteria:

• Significant pathological findings on brain MRI at screening including, but not limited to, evidence of vasogenic edema, 4 or more microhemorrhages, any macrohemorrhages, any superficial siderosis, or severe white matter disease.
• Any anticoagulants or have a bleeding disorder that is not adequately controlled.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ABBVIE CALL CENTER; 844-663-3742; abbvieclinicaltrials@abbvie.com

• Listed Location Countries: United States
• Removed Location Countries: Canada, Italy, Japan, Portugal, Spain

Administrative Information

• NCT Number: NCT05291234
• Other Study ID Numbers: M22-721; 2022-500691-59-00 ( Other Identifier: EU CT )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• URL: https://vivli.org/ourmember/abbvie/

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: April 2024