A Study to Assess the Safety and Effects of ABBV-1758 Following Subcutaneous or Intravenous Injections in Participants With Alzheimer's Disease

Condition(s) studied

Investigational drug(s) / intervention(s)

ABBV-1758: Intravenous (IV) or Subcutaneous (SC)

Placebo for ABBV-1758: Intravenous (IV) or Subcutaneous (SC)

ABBV-1758: Subcutaneous (SC)

Placebo for ABBV-1758: Subcutaneous (SC)

Study 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. The purpose of this study is to test how safe ABBV-1758 is, how well it works, how the body processes it and what effects it has on the body.

ABBV-1758 is an investigational drug being developed for the treatment of Alzheimer's disease. This study is conducted in 3 stages. Stage A is a multiple ascending dose study with a 1 in 5 chance (4:1 randomization) that participants are assigned to receive placebo. Stage B is a dose expansion phase, also using 4:1 randomization for ABBV-1758 or placebo. Stage C enrolls Japanese and Chinese participants with the same randomization scheme. Approximately 210 participants will be enrolled at about 55 sites in the United States, China, and Japan.

Participants will receive intravenous (IV) or subcutaneous (SC) doses of ABBV-1758 or placebo once every 4 weeks (Q4W) for 24 weeks and will be followed for additional 12 weeks in the Follow-up Period. Participants will have the option of participating in a 12-month, blinded Extension Period receiving ABBV-1758 or placebo based on amyloid PET results.

There may be higher treatment burden for participants in this trial compared to their standard of care due to study procedures. Participants will attend regular visits during the study at a hospital or clinic. The safety of the treatment will be checked by medical assessments, blood tests, and completing questionnaires.

Eligibility

Primary outcome measure(s)

• Percentage of Participants Experiencing Adverse Events (AEs) — Up to approximately 40 weeks
  An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. The investigator assesses the relationship of each event to the use of study drug.
• Percentage of Participants with Abnormal Change from Baseline in Clinical Laboratory Test Results — Up to approximately 40 weeks
  Number of participants with abnormal change in clinical laboratory test results like hematology will be assessed.
• Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA) — Up to approximately 40 weeks
  Amyloid related imaging abnormalities represent a spectrum of magnetic resonance imaging findings primarily observed in participants undergoing treatment with anti-amyloid therapies.
• Percentage of Participants with Abnormal Change From Baseline in Vital Sign Measurements — Up to approximately 40 weeks
  Number of participants with abnormal change from baseline in vital sign measurements like systolic and diastolic blood pressure will be assessed.
• Percentage of Participants with Abnormal Change From Baseline in Electrocardiograms (ECGs) Parameters — Up to approximately 40 weeks
  12-lead resting ECGs will be recorded. Parameters include heart rate, PR interval, QT interval, QRS duration, and QT interval corrected using Fridericia's formula (QTcF).
• Percentage of Participants Experiencing Any Suicidal Ideation or Suicidal Behavior As Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) — Up to approximately 40 weeks
  The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior, with a higher score denoting more severe suicidal ideation and behavior.
• Stage A, B, and C: Change from Baseline in Brain Amyloid Load — Up to approximately 28 Weeks
  Measured by amyloid positron emission tomography (PET)
• Stage A and C: Maximum Plasma Concentration (Cmax) of ABBV-1758 — Up to approximately 40 weeks
  Cmax of ABBV-1758
• Stage A and C: Time to Cmax (Tmax) of ABBV-1758 — Up to approximately 40 weeks
  Tmax of ABBV-1758
• Stage A and C: Trough Concentration measured at the end of a dosing interval at steady state (Ctrough) of ABBV-1758 — Up to approximately 40 weeks
  Ctrough of ABBV-1758
• Stage A and C: Area under the Plasma Concentration-time Curve from Time Zero to the End of the Dosing Interval (AUCtau) of ABBV-1758 — Up to approximately 40 weeks
  AUCtau of ABBV-1758
• Stage A and C: Average Serum Concentration at Steady-State (Cav,ss) of ABBV-1758 — Up to approximately 40 weeks
  Cav,ss of ABBV-1758
• Stage A and C: Accumulation ratio for (AUCtau) of ABBV-1758 — Up to approximately 40 weeks
  AUCtau of ABBV-1758
• Stage A and C: Total Body Clearance (CL) of ABBV-1758 — Up to approximately 40 weeks
  CL of ABBV-1758
• Stage A and C: Apparent Clearance (CL/F) of ABBV-1758 — Up to approximately 40 weeks
  CL/F of ABBV-1758
• Stage A and C: Volume of Distribution at Steady-State (Vss) — Up to approximately 40 weeks
  Vss of ABBV-1758
• Stage A and C: Apparent Volume of Distribution during the Terminal Phase (Vz) — Up to approximately 40 weeks
  Vz of ABBV-1758
• Stage A and C: Terminal Phase Elimination Rate Constant (β) of ABBV-1758 — Up to approximately 40 weeks
  β of ABBV-1758
• Stage A and C: Terminal Phase Elimination Half-Life (t1/2) of ABBV-1758 — Up to approximately 40 weeks
  Terminal phase elimination half-life of ABBV-1758
• Stage A and C: Effective Half-Life (T1/2,eff) — Up to approximately 40 weeks
  T1/2,eff of ABBV-1758

Trial sites (12)

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