Alzheimer's Disease
Conditions
Keywords
Randomized, Safety Study, Adaptive, Double Blind
Brief summary
This is a study to evaluate the safety of multiple doses of AAB-003 (PF-05236812) in patients with mild to moderate Alzheimer's Disease. Patients will receive either AAB-003 (PF-05236812) or placebo. Each patient's participation will last approximately 41 weeks.
Interventions
0.5 mg/kg AAB-003, IV
OTHERPlacebo
Placebo, IV
Sponsors
JANSSEN Alzheimer Immunotherapy Research & Development, LLC
Pfizer
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of probable Alzheimer's Disease with MMSE score of 16-26, and brain MRI consistent with the diagnosis of Alzheimer's Disease * Concurrent use of cholinesterase inhibitor or memantine allowed, if stable. * Caregiver will participate and be able to attend clinic visits with patient
Exclusion criteria
* Significant neurological disease other than Alzheimer's Disease * Major psychiatric disorder * Contraindication to undergo brain MRI (e.g., pacemaker, CSF shunt, or foreign metal objects in the body) * Women of childbearing potential
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Baseline, Weeks 1,13,16,26,39 or Early Withdrawal | Criteria for ECG values of potential clinical concern are: interval between the start of the ECG P wave and the start of the QRS complex corresponding to the time between onset of atrial depolarization and onset of ventricular depolarization (PR): \>= 300 milliseconds (msec), and \>=25% increase when baseline \>=200 msec/ \>=50% increase when baseline less than or equal to (\<=) 200 msec; time from ECG Q wave to the end of S wave corresponding to ventricular depolarization (QRS): \>=200 msec, and \>=25% increase when baseline \>100 msec/ \>=50% increase when baseline \<=100 msec; QTc using Fridericia's formula (QTcF) interval: 450 to \<480 msec, \>=480 msec; QTcF change from baseline: 30 to \<60 msec, and \>=60 msec. |
| Number of Participants With Abnormal Physical Examination Findings | Baseline up to 39 Weeks and at Early Withdrawal | — |
| Number of Participants With Abnormal Neurological Examination Findings | Screening, Day 1 (Baseline) and Weeks 1,6,13,19,26,32, and 39, and at Early Withdrawal | The neurological examination was done to the extent needed to assess the participant for any potential changes in neurological status, as determined by the investigator. The minimum items assessed were level of consciousness, speech, cranial nerves, motor, sensory, coordination, gait, and tendon reflexes. |
| Maximum Observed Serum Concentration (Cmax) for AAB-003 at Day 1 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. | — |
| Maximum Observed Serum Concentration (Cmax) for AAB-003 at at Week 26 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. | — |
| Average Concentration (Cavg) for AAB-003 in Serum at Day 1 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. | — |
| Average Concentration (Cavg) for AAB-003 in Serum at Week 26 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. | — |
| Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Day 1 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. | — |
| Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Week 26 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for AAB-003 in Serum at Day 1 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. | — |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for AAB-003 in Serum at Day 1 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. | — |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Day 1 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. | — |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Week 26 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. | — |
| Systemic Clearance (CL) for AAB-003 in Serum at Day 1 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. | — |
| Systemic Clearance (CL) for AAB-003 in Serum at Week 26 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. | — |
| Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Day 1 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. | — |
| Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Week 26 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. | — |
| Serum Decay Half-Life (t1/2) for AAB-003 at Day 1 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. | — |
| Serum Decay Half-Life (t1/2) for AAB-003 at Week 26 | Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. | — |
| Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | Baseline up to Week 39 or Early Withdrawal | The C-SSRS assessed whether the participant experienced the following: completed suicide (1), suicide attempt (2) (response of Yes on actual attempt), preparatory acts toward imminent suicidal behavior (3)(Yes on preparatory acts or behavior), suicidal ideation (4) (Yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7)(Yes on Has participant engaged in non-suicidal self-injurious behavior). |
| Number of Participants With New Occurrence of Brain Magnetic Resonance Imaging (MRI) Finding | Baseline up to Week 32. | Brain MRIs were collected during the course of study to assess for any potential drug-related changes that might have constituted a safety concern for study participants. Findings suggestive of either vasogenic edema (VE) or intracranial hemorrhage represented adverse events of special circumstance and were to be reported immediately. |
| Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Day 1, Week 13, and Week 26 | VE of the brain, identified via MRI, was identified as an adverse event of special circumstance. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Baseline up to 39 Weeks and at Early Withdrawal | — |
| Number of Participants With Laboratory Abnormalities | Baseline up to 39 Weeks and at Early Withdrawal | — |
| Number of Participants With Vital Signs of Potential Clinical Concern | Baseline up to 39 Weeks and at Early Withdrawal | Criteria for potential clinical concern in vital signs included: supine/sitting pulse rate of less than (\<) 40 or more than (\>) 120 beats per minute (bpm), and standing pulse rate of \<40 or \>140 bpm; systolic blood pressure (SBP) of more than or equal to (\>=)30 millimeters of mercury (mm Hg) change from baseline in same posture and \<90 mm Hg; diastolic blood pressure (DBP) \>=20 mm Hg change from baseline in same posture and \<50 mm Hg. Only supine vital signs were planned for this study. Unplanned sitting vital signs were collected only in the 8/mg and placebo groups and also reported. |
Other
| Measure | Time frame | Description |
|---|---|---|
| CSF P-tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Baseline and Week 32 | — |
| Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Day 1 (predose), Week 13 (predose), Week 26 (predose) and Week 39 or Early Withdrawal | Human serum anti-drug antibodies (ADA) samples were analyzed for the presence or absence of anti-AAB-003 antibodies by enzyme-linked immunosorbent assay (ELISA) method |
| Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Baseline, Weeks 13, 26 and 39 | The ADAS-cog 70 Point is a structured scale (approximately 40 min to complete) that evaluates memory, orientation, attention, reasoning, language and constructional praxis. This study used the 11-item cognitive subscale of the ADAS-Cog with scores ranging from 0 to 70 points; higher scores indicated greater cognitive impairment. |
| Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Baseline, Weeks 13, 26 and 39 | The DAD is a functional assessment based on an interview with the caregiver that takes approximately 20 min to administer and it is comprised of 40 items, 17 related to self-care and 23 items involving instrumental activities of daily living. The DAD is scored from 0 to 100 (higher scores indicate better functioning). |
| Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Baseline, Weeks 13, 26 and 39 | The NPI is an instrument used to assess changes of behavior that have appeared in a defined period of time in participants with Alzheimer's disease (AD) and other dementias. Twelve (12) behavioral areas are assessed in the NPI - delusions, apathy, hallucinations, disinhibition, agitation, irritability, depression, aberrant motor behavior, anxiety, nighttime behaviors, euphoria, appetite, and eating changes. The NPI score is based on frequency and severity of specific behaviors within these categories as reported by the caregiver. A separate caregiver distress score may also be included. The NPI ranges from 0 to 144 (higher scores indicate greater psychopathology). |
| Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Baseline, Weeks 26 and 39 | The CDR scale is a clinician-rated dementia staging instrument that tracks the progression of cognitive impairment in the following 6 categories - memory, orientation, judgment and problem solving, involvement in community affairs, home and hobbies, and personal care based on the CDR interview. The CDR is based on discussions between the clinician with the participant and caregiver using a structured format. A global CDR score is established by clinical scoring rules with values of 0 (no dementia), 0.5 (questionable dementia), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia). A more quantitative version of the CDR scale is obtained by summing up the ratings in each of the 6 categories to provide the (CDR-SB). The CDR-SB scale ranges from 0 to 18 where higher score indicates severe dementia. |
| Change From Baseline in CSF Tau Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups | Baseline and Week 32 | — |
| Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Baseline, Weeks 13, 26 and 39 | The MMSE is a brief 30-point questionnaire test that is used to assess cognition. It is commonly used to screen for dementia. In the time span of about 10 min, it samples various functions, including arithmetic, memory and orientation. Scores range from 0 to 30 (higher scores indicate less impairment) and participants with scores of 16 to 26 were eligible. |
| Cerebrospinal Fluid (CSF) Concentration of AAB-003 at Week 32 | Week 32 or Early Withdrawal | Participants enrolled in the 2, 4 and 8 mg/kg cohorts participated in an optional CSF collection. Participants enrolled in the maximum tolerated dose (MTD) cohort were mandatorily collected for CSF. |
| Change From Baseline in CSF Amyloid-beta x-40 Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups | Baseline and Week 32 | — |
| CSF Amyloid-beta x-40 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Baseline and Week 32 | — |
| Change From Baseline in CSF Amyloid-beta x-42 Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups | Baseline and Week 32 | — |
| CSF Amyloid-beta x-42 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Baseline and Week 32 | — |
| CSF Tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Baseline and Week 32 | — |
| Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40 | Weeks 1, 3, 6, 10, 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40 | Weeks 1, 3, 6, 10, 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Amyloid-Beta x-40 | Baseline; Day 2 (24 hours post start of infusion); Weeks 1, 6, and 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. | — |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Amyloid-Beta x-40 | Baseline; Day 2 (24 hours post start of infusion); Weeks 1, 6, and 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. | — |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40 | Weeks 1, 3, 6, 10, 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. | — |
| Plasma Decay Half-Life (t1/2) for Amyloid-Beta x-40 | Baseline; Day 2 (24 hours post start of infusion); Weeks 1, 6, and 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. | — |
| Change From Baseline in CSF P-tau Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups | Baseline and Week 32 | — |
Countries
South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AAB-003 0.5 mg/kg Participants received AAB-003 0.5 mg/kg by IV infusion on Day 1, Week 13 and Week 26 | 6 |
| AAB-003 1 mg/kg Participants received AAB-003 1 mg/kg by IV infusion on Day 1, Week 13 and Week 26 | 6 |
| AAB-003 2 mg/kg Participants received AAB-003 2 mg/kg by IV infusion on Day 1, Week 13 and Week 26 | 16 |
| AAB-003 4 mg/kg Participants received AAB-003 4 mg/kg by IV infusion on Day 1, Week 13 and Week 26 | 17 |
| AAB-003 8 mg/kg Participants received AAB-003 8 mg/kg by IV infusion on Day 1, Week 13 and Week 26 | 24 |
| Placebo Participants received placebo matched to AAB-003 by IV infusion on Day 1, Week 13 and Week 26 | 19 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 2 |
| Overall Study | Other | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 | 3 | 3 | 0 |
Baseline characteristics
| Characteristic | AAB-003 0.5 mg/kg | AAB-003 1 mg/kg | AAB-003 2 mg/kg | AAB-003 4 mg/kg | AAB-003 8 mg/kg | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 64.5 Years STANDARD_DEVIATION 6.4 | 67.2 Years STANDARD_DEVIATION 7.4 | 70.7 Years STANDARD_DEVIATION 10.8 | 71.5 Years STANDARD_DEVIATION 8.8 | 64.5 Years STANDARD_DEVIATION 7.6 | 71.1 Years STANDARD_DEVIATION 7.6 | 68.6 Years STANDARD_DEVIATION 8.8 |
| Gender Female | 4 Participants | 3 Participants | 14 Participants | 9 Participants | 14 Participants | 8 Participants | 52 Participants |
| Gender Male | 2 Participants | 3 Participants | 2 Participants | 8 Participants | 10 Participants | 11 Participants | 36 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 10 Participants | 11 Participants | 11 Participants | 5 Participants | 38 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 3 Participants | 5 Participants | 6 Participants | 12 Participants | 11 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 6 | 3 / 6 | 10 / 16 | 8 / 17 | 10 / 24 | 12 / 19 |
| serious Total, serious adverse events | 1 / 6 | 1 / 6 | 1 / 16 | 0 / 17 | 5 / 24 | 0 / 19 |
Outcome results
Primary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Day 1
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
Population: Evaluable participants in the PK analysis set (all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Day 1 | 5384 mcg*hr/mL | Geometric Coefficient of Variation 30 |
| AAB-003 1 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Day 1 | 14300 mcg*hr/mL | Geometric Coefficient of Variation 33 |
| AAB-003 2 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Day 1 | 23660 mcg*hr/mL | Geometric Coefficient of Variation 16 |
| AAB-003 4 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Day 1 | 44490 mcg*hr/mL | Geometric Coefficient of Variation 20 |
| AAB-003 8 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Day 1 | 80320 mcg*hr/mL | Geometric Coefficient of Variation 24 |
Primary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Week 26
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.
Population: Evaluable participants in the PK analysis set (all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Week 26 | 7502 mcg*hr/mL | Geometric Coefficient of Variation 22 |
| AAB-003 1 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Week 26 | 15660 mcg*hr/mL | Geometric Coefficient of Variation 9 |
| AAB-003 2 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Week 26 | 27440 mcg*hr/mL | Geometric Coefficient of Variation 28 |
| AAB-003 4 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Week 26 | 49180 mcg*hr/mL | Geometric Coefficient of Variation 29 |
| AAB-003 8 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Week 26 | 100700 mcg*hr/mL | Geometric Coefficient of Variation 34 |
Primary
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for AAB-003 in Serum at Day 1
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
Population: Evaluable participants in the PK analysis set (all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for AAB-003 in Serum at Day 1 | 5597 mcg*hr/mL | Geometric Coefficient of Variation 39 |
| AAB-003 1 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for AAB-003 in Serum at Day 1 | 13060 mcg*hr/mL | Geometric Coefficient of Variation 18 |
| AAB-003 2 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for AAB-003 in Serum at Day 1 | 25270 mcg*hr/mL | Geometric Coefficient of Variation 17 |
| AAB-003 4 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for AAB-003 in Serum at Day 1 | 46430 mcg*hr/mL | Geometric Coefficient of Variation 21 |
| AAB-003 8 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for AAB-003 in Serum at Day 1 | 82140 mcg*hr/mL | Geometric Coefficient of Variation 23 |
Primary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for AAB-003 in Serum at Day 1
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
Population: PK Analysis Set consisted of all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for AAB-003 in Serum at Day 1 | 5397 mcg*hr/mL | Geometric Coefficient of Variation 30 |
| AAB-003 1 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for AAB-003 in Serum at Day 1 | 13470 mcg*hr/mL | Geometric Coefficient of Variation 33 |
| AAB-003 2 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for AAB-003 in Serum at Day 1 | 22960 mcg*hr/mL | Geometric Coefficient of Variation 19 |
| AAB-003 4 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for AAB-003 in Serum at Day 1 | 44000 mcg*hr/mL | Geometric Coefficient of Variation 20 |
| AAB-003 8 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for AAB-003 in Serum at Day 1 | 79130 mcg*hr/mL | Geometric Coefficient of Variation 23 |
Primary
Average Concentration (Cavg) for AAB-003 in Serum at Day 1
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
Population: Evaluable participants in the PK analysis set (all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Average Concentration (Cavg) for AAB-003 in Serum at Day 1 | 2.465 mcg/mL | Geometric Coefficient of Variation 30 |
| AAB-003 1 mg/kg | Average Concentration (Cavg) for AAB-003 in Serum at Day 1 | 6.545 mcg/mL | Geometric Coefficient of Variation 33 |
| AAB-003 2 mg/kg | Average Concentration (Cavg) for AAB-003 in Serum at Day 1 | 10.83 mcg/mL | Geometric Coefficient of Variation 16 |
| AAB-003 4 mg/kg | Average Concentration (Cavg) for AAB-003 in Serum at Day 1 | 20.37 mcg/mL | Geometric Coefficient of Variation 20 |
| AAB-003 8 mg/kg | Average Concentration (Cavg) for AAB-003 in Serum at Day 1 | 36.78 mcg/mL | Geometric Coefficient of Variation 24 |
Primary
Average Concentration (Cavg) for AAB-003 in Serum at Week 26
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.
Population: Evaluable participants in the PK analysis set (all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Average Concentration (Cavg) for AAB-003 in Serum at Week 26 | 3.435 mcg/mL | Geometric Coefficient of Variation 22 |
| AAB-003 1 mg/kg | Average Concentration (Cavg) for AAB-003 in Serum at Week 26 | 7.171 mcg/mL | Geometric Coefficient of Variation 9 |
| AAB-003 2 mg/kg | Average Concentration (Cavg) for AAB-003 in Serum at Week 26 | 12.56 mcg/mL | Geometric Coefficient of Variation 28 |
| AAB-003 4 mg/kg | Average Concentration (Cavg) for AAB-003 in Serum at Week 26 | 22.52 mcg/mL | Geometric Coefficient of Variation 29 |
| AAB-003 8 mg/kg | Average Concentration (Cavg) for AAB-003 in Serum at Week 26 | 46.12 mcg/mL | Geometric Coefficient of Variation 34 |
Primary
Maximum Observed Serum Concentration (Cmax) for AAB-003 at at Week 26
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.
Population: Evaluable participants in the PK analysis set (all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Maximum Observed Serum Concentration (Cmax) for AAB-003 at at Week 26 | 14.53 mcg/mL | Geometric Coefficient of Variation 33 |
| AAB-003 1 mg/kg | Maximum Observed Serum Concentration (Cmax) for AAB-003 at at Week 26 | 38.51 mcg/mL | Geometric Coefficient of Variation 25 |
| AAB-003 2 mg/kg | Maximum Observed Serum Concentration (Cmax) for AAB-003 at at Week 26 | 60.17 mcg/mL | Geometric Coefficient of Variation 38 |
| AAB-003 4 mg/kg | Maximum Observed Serum Concentration (Cmax) for AAB-003 at at Week 26 | 108.5 mcg/mL | Geometric Coefficient of Variation 41 |
| AAB-003 8 mg/kg | Maximum Observed Serum Concentration (Cmax) for AAB-003 at at Week 26 | 228.9 mcg/mL | Geometric Coefficient of Variation 30 |
Primary
Maximum Observed Serum Concentration (Cmax) for AAB-003 at Day 1
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
Population: Pharmacokinetic (PK) Analysis Set consisted of all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Maximum Observed Serum Concentration (Cmax) for AAB-003 at Day 1 | 13.79 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 48 |
| AAB-003 1 mg/kg | Maximum Observed Serum Concentration (Cmax) for AAB-003 at Day 1 | 32.05 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 33 |
| AAB-003 2 mg/kg | Maximum Observed Serum Concentration (Cmax) for AAB-003 at Day 1 | 58.74 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 21 |
| AAB-003 4 mg/kg | Maximum Observed Serum Concentration (Cmax) for AAB-003 at Day 1 | 122.4 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 14 |
| AAB-003 8 mg/kg | Maximum Observed Serum Concentration (Cmax) for AAB-003 at Day 1 | 223.7 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 28 |
Primary
Number of Participants With Abnormal Neurological Examination Findings
The neurological examination was done to the extent needed to assess the participant for any potential changes in neurological status, as determined by the investigator. The minimum items assessed were level of consciousness, speech, cranial nerves, motor, sensory, coordination, gait, and tendon reflexes.
Time frame: Screening, Day 1 (Baseline) and Weeks 1,6,13,19,26,32, and 39, and at Early Withdrawal
Population: Safety analysis set consisted of all participants who received at least one infusion of study medication (including partial infusions). n = number of evaluable participants at the corresponding time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 26 (n=6,5,14,14,18,19) | 2 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 13 (n=6,6,15,16,22,19) | 1 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 1 (n=6,6,16,17,24,19) | 1 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 6 (n=6,6,16,17,24,19) | 1 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Day 1 (n=6,6,16,17,24,19) | 1 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 19 (n=6,5,14,15,21,19) | 1 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 32 (n=6,5,14,14,19,18) | 1 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 39 (n=6,4,14,14,19,17) | 1 Participants |
| AAB-003 1 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 39 (n=6,4,14,14,19,17) | 1 Participants |
| AAB-003 1 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 26 (n=6,5,14,14,18,19) | 1 Participants |
| AAB-003 1 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 19 (n=6,5,14,15,21,19) | 1 Participants |
| AAB-003 1 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 1 (n=6,6,16,17,24,19) | 1 Participants |
| AAB-003 1 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 32 (n=6,5,14,14,19,18) | 1 Participants |
| AAB-003 1 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Day 1 (n=6,6,16,17,24,19) | 2 Participants |
| AAB-003 1 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 6 (n=6,6,16,17,24,19) | 1 Participants |
| AAB-003 1 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 13 (n=6,6,15,16,22,19) | 1 Participants |
| AAB-003 2 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 26 (n=6,5,14,14,18,19) | 1 Participants |
| AAB-003 2 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 6 (n=6,6,16,17,24,19) | 2 Participants |
| AAB-003 2 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 32 (n=6,5,14,14,19,18) | 1 Participants |
| AAB-003 2 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 19 (n=6,5,14,15,21,19) | 1 Participants |
| AAB-003 2 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 13 (n=6,6,15,16,22,19) | 4 Participants |
| AAB-003 2 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Day 1 (n=6,6,16,17,24,19) | 2 Participants |
| AAB-003 2 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 1 (n=6,6,16,17,24,19) | 2 Participants |
| AAB-003 2 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 39 (n=6,4,14,14,19,17) | 1 Participants |
| AAB-003 4 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 32 (n=6,5,14,14,19,18) | 2 Participants |
| AAB-003 4 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 6 (n=6,6,16,17,24,19) | 3 Participants |
| AAB-003 4 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 13 (n=6,6,15,16,22,19) | 3 Participants |
| AAB-003 4 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 19 (n=6,5,14,15,21,19) | 4 Participants |
| AAB-003 4 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Day 1 (n=6,6,16,17,24,19) | 3 Participants |
| AAB-003 4 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 1 (n=6,6,16,17,24,19) | 3 Participants |
| AAB-003 4 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 26 (n=6,5,14,14,18,19) | 2 Participants |
| AAB-003 4 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 39 (n=6,4,14,14,19,17) | 4 Participants |
| AAB-003 8 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 19 (n=6,5,14,15,21,19) | 1 Participants |
| AAB-003 8 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 13 (n=6,6,15,16,22,19) | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 32 (n=6,5,14,14,19,18) | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 39 (n=6,4,14,14,19,17) | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 6 (n=6,6,16,17,24,19) | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 26 (n=6,5,14,14,18,19) | 1 Participants |
| AAB-003 8 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Week 1 (n=6,6,16,17,24,19) | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Abnormal Neurological Examination Findings | Day 1 (n=6,6,16,17,24,19) | 1 Participants |
| Placebo | Number of Participants With Abnormal Neurological Examination Findings | Week 1 (n=6,6,16,17,24,19) | 5 Participants |
| Placebo | Number of Participants With Abnormal Neurological Examination Findings | Day 1 (n=6,6,16,17,24,19) | 6 Participants |
| Placebo | Number of Participants With Abnormal Neurological Examination Findings | Week 19 (n=6,5,14,15,21,19) | 4 Participants |
| Placebo | Number of Participants With Abnormal Neurological Examination Findings | Week 26 (n=6,5,14,14,18,19) | 7 Participants |
| Placebo | Number of Participants With Abnormal Neurological Examination Findings | Week 13 (n=6,6,15,16,22,19) | 4 Participants |
| Placebo | Number of Participants With Abnormal Neurological Examination Findings | Week 32 (n=6,5,14,14,19,18) | 6 Participants |
| Placebo | Number of Participants With Abnormal Neurological Examination Findings | Week 39 (n=6,4,14,14,19,17) | 6 Participants |
| Placebo | Number of Participants With Abnormal Neurological Examination Findings | Week 6 (n=6,6,16,17,24,19) | 5 Participants |
Primary
Number of Participants With Abnormal Physical Examination Findings
Time frame: Baseline up to 39 Weeks and at Early Withdrawal
Population: Safety analysis set consisted of all participants who received at least one infusion of study medication (including partial infusions). A full physical examination consisted of abdomen, genitourinary, cardiovascular systems, lungs, lymph nodes, mouth, musculoskeletal, general, skin, extremities, head, ears, eyes, nose, throat and thyroid.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AAB-003 0.5 mg/kg | Number of Participants With Abnormal Physical Examination Findings | 2 Participants |
| AAB-003 1 mg/kg | Number of Participants With Abnormal Physical Examination Findings | 4 Participants |
| AAB-003 2 mg/kg | Number of Participants With Abnormal Physical Examination Findings | 1 Participants |
| AAB-003 4 mg/kg | Number of Participants With Abnormal Physical Examination Findings | 5 Participants |
| AAB-003 8 mg/kg | Number of Participants With Abnormal Physical Examination Findings | 9 Participants |
| Placebo | Number of Participants With Abnormal Physical Examination Findings | 9 Participants |
Primary
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS assessed whether the participant experienced the following: completed suicide (1), suicide attempt (2) (response of Yes on actual attempt), preparatory acts toward imminent suicidal behavior (3)(Yes on preparatory acts or behavior), suicidal ideation (4) (Yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7)(Yes on Has participant engaged in non-suicidal self-injurious behavior).
Time frame: Baseline up to Week 39 or Early Withdrawal
Population: Safety Analysis Set included all participants who received at least one infusion of study medication (including partial infusions).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AAB-003 0.5 mg/kg | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | 1 Participants |
| AAB-003 4 mg/kg | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | 1 Participants |
| Placebo | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | 2 Participants |
Primary
Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria
Criteria for ECG values of potential clinical concern are: interval between the start of the ECG P wave and the start of the QRS complex corresponding to the time between onset of atrial depolarization and onset of ventricular depolarization (PR): \>= 300 milliseconds (msec), and \>=25% increase when baseline \>=200 msec/ \>=50% increase when baseline less than or equal to (\<=) 200 msec; time from ECG Q wave to the end of S wave corresponding to ventricular depolarization (QRS): \>=200 msec, and \>=25% increase when baseline \>100 msec/ \>=50% increase when baseline \<=100 msec; QTc using Fridericia's formula (QTcF) interval: 450 to \<480 msec, \>=480 msec; QTcF change from baseline: 30 to \<60 msec, and \>=60 msec.
Time frame: Baseline, Weeks 1,13,16,26,39 or Early Withdrawal
Population: Safety Analysis Set included all participants who received an infusion of study medication (including partial infusions).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Increase from Baseline 30 to <60 msec | 2 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | QRS Complex >=25/50% increase | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval 450 to <480 msec | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | PR Interval >=25/50% increase | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum PR Interval >=300 msec | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval 480 to <500 msec | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval Increase >=60 msec | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval >=500 msec | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QRS Complex >=200 msec | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Increase from Baseline 30 to <60 msec | 1 Participants |
| AAB-003 1 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | QRS Complex >=25/50% increase | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | PR Interval >=25/50% increase | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum PR Interval >=300 msec | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval 480 to <500 msec | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QRS Complex >=200 msec | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval 450 to <480 msec | 2 Participants |
| AAB-003 1 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval Increase >=60 msec | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval >=500 msec | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | PR Interval >=25/50% increase | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval 450 to <480 msec | 5 Participants |
| AAB-003 2 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval 480 to <500 msec | 1 Participants |
| AAB-003 2 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval >=500 msec | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum PR Interval >=300 msec | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Increase from Baseline 30 to <60 msec | 2 Participants |
| AAB-003 2 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval Increase >=60 msec | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QRS Complex >=200 msec | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | QRS Complex >=25/50% increase | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval 450 to <480 msec | 4 Participants |
| AAB-003 4 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum PR Interval >=300 msec | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval Increase >=60 msec | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | QRS Complex >=25/50% increase | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | PR Interval >=25/50% increase | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval >=500 msec | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Increase from Baseline 30 to <60 msec | 1 Participants |
| AAB-003 4 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval 480 to <500 msec | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QRS Complex >=200 msec | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QRS Complex >=200 msec | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval 480 to <500 msec | 1 Participants |
| AAB-003 8 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval 450 to <480 msec | 4 Participants |
| AAB-003 8 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval >=500 msec | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum PR Interval >=300 msec | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | PR Interval >=25/50% increase | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval Increase >=60 msec | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Increase from Baseline 30 to <60 msec | 2 Participants |
| AAB-003 8 mg/kg | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | QRS Complex >=25/50% increase | 0 Participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval >=500 msec | 0 Participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | QRS Complex >=25/50% increase | 1 Participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval 480 to <500 msec | 0 Participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval Increase >=60 msec | 0 Participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Interval 450 to <480 msec | 3 Participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QRS Complex >=200 msec | 0 Participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum PR Interval >=300 msec | 0 Participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | Maximum QTcF Increase from Baseline 30 to <60 msec | 3 Participants |
| Placebo | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria | PR Interval >=25/50% increase | 0 Participants |
Primary
Number of Participants With Laboratory Abnormalities
Time frame: Baseline up to 39 Weeks and at Early Withdrawal
Population: Safety analysis set consisted of all participants who received at least one infusion of study medication (including partial infusions). Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AAB-003 0.5 mg/kg | Number of Participants With Laboratory Abnormalities | 3 Participants |
| AAB-003 1 mg/kg | Number of Participants With Laboratory Abnormalities | 3 Participants |
| AAB-003 2 mg/kg | Number of Participants With Laboratory Abnormalities | 11 Participants |
| AAB-003 4 mg/kg | Number of Participants With Laboratory Abnormalities | 10 Participants |
| AAB-003 8 mg/kg | Number of Participants With Laboratory Abnormalities | 12 Participants |
| Placebo | Number of Participants With Laboratory Abnormalities | 13 Participants |
Primary
Number of Participants With New Occurrence of Brain Magnetic Resonance Imaging (MRI) Finding
Brain MRIs were collected during the course of study to assess for any potential drug-related changes that might have constituted a safety concern for study participants. Findings suggestive of either vasogenic edema (VE) or intracranial hemorrhage represented adverse events of special circumstance and were to be reported immediately.
Time frame: Baseline up to Week 32.
Population: Safety Analysis Set included all participants who received an infusion of study medication (including partial infusions).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AAB-003 0.5 mg/kg | Number of Participants With New Occurrence of Brain Magnetic Resonance Imaging (MRI) Finding | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With New Occurrence of Brain Magnetic Resonance Imaging (MRI) Finding | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With New Occurrence of Brain Magnetic Resonance Imaging (MRI) Finding | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With New Occurrence of Brain Magnetic Resonance Imaging (MRI) Finding | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With New Occurrence of Brain Magnetic Resonance Imaging (MRI) Finding | 5 Participants |
| Placebo | Number of Participants With New Occurrence of Brain Magnetic Resonance Imaging (MRI) Finding | 0 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Baseline up to 39 Weeks and at Early Withdrawal
Population: Safety analysis set consisted of all participants who received at least one infusion of study medication (including partial infusions). A TEAE was defined as an untoward medical occurrence reported by the participant or investigator following administration of at least one dose of AAB-003.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Serious Adverse Events (SAEs) | 1 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Adverse Events (AEs) | 5 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants Discontinued due to AEs | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Serious Adverse Events (SAEs) | 1 Participants |
| AAB-003 1 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Adverse Events (AEs) | 3 Participants |
| AAB-003 1 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants Discontinued due to AEs | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Serious Adverse Events (SAEs) | 1 Participants |
| AAB-003 2 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Adverse Events (AEs) | 10 Participants |
| AAB-003 2 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants Discontinued due to AEs | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Serious Adverse Events (SAEs) | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Adverse Events (AEs) | 8 Participants |
| AAB-003 4 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants Discontinued due to AEs | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Serious Adverse Events (SAEs) | 5 Participants |
| AAB-003 8 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Adverse Events (AEs) | 16 Participants |
| AAB-003 8 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants Discontinued due to AEs | 3 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Adverse Events (AEs) | 12 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants Discontinued due to AEs | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Serious Adverse Events (SAEs) | 0 Participants |
Primary
Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit
VE of the brain, identified via MRI, was identified as an adverse event of special circumstance.
Time frame: Day 1, Week 13, and Week 26
Population: Safety Analysis Set included all participants who received an infusion of study medication, including partial infusions. n = number of evaluable participants at the corresponding timeframe.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Week 13 (n=6,5,15,16,21,17) | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Day 1 (n=6,6,16,17,24,19) | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Week 26 (n=6,5,14,14,17,16) | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Week 13 (n=6,5,15,16,21,17) | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Day 1 (n=6,6,16,17,24,19) | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Week 26 (n=6,5,14,14,17,16) | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Week 13 (n=6,5,15,16,21,17) | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Day 1 (n=6,6,16,17,24,19) | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Week 26 (n=6,5,14,14,17,16) | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Week 13 (n=6,5,15,16,21,17) | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Day 1 (n=6,6,16,17,24,19) | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Week 26 (n=6,5,14,14,17,16) | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Week 13 (n=6,5,15,16,21,17) | 1 Participants |
| AAB-003 8 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Day 1 (n=6,6,16,17,24,19) | 1 Participants |
| AAB-003 8 mg/kg | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Week 26 (n=6,5,14,14,17,16) | 0 Participants |
| Placebo | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Day 1 (n=6,6,16,17,24,19) | 0 Participants |
| Placebo | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Week 26 (n=6,5,14,14,17,16) | 0 Participants |
| Placebo | Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit | Week 13 (n=6,5,15,16,21,17) | 0 Participants |
Primary
Number of Participants With Vital Signs of Potential Clinical Concern
Criteria for potential clinical concern in vital signs included: supine/sitting pulse rate of less than (\<) 40 or more than (\>) 120 beats per minute (bpm), and standing pulse rate of \<40 or \>140 bpm; systolic blood pressure (SBP) of more than or equal to (\>=)30 millimeters of mercury (mm Hg) change from baseline in same posture and \<90 mm Hg; diastolic blood pressure (DBP) \>=20 mm Hg change from baseline in same posture and \<50 mm Hg. Only supine vital signs were planned for this study. Unplanned sitting vital signs were collected only in the 8/mg and placebo groups and also reported.
Time frame: Baseline up to 39 Weeks and at Early Withdrawal
Population: Safety analysis set consisted of all participants who received at least one infusion of study medication (including partial infusions).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine pulse rate <40 or >120 bpm | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting pulse rate <40 or >120 bpm | NA Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting DBP <50 mm Hg | NA Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum decrease in supine DBP >=20 mm Hg | 1 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum increase in supine DBP >=20 mm Hg | 2 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting SBP <90 mm Hg | NA Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine DBP <50 mm Hg | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum decrease in supine SBP >=30 mm Hg | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum increase in supine SBP >=30 mm Hg | 3 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine SBP <90 mm Hg | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting SBP <90 mm Hg | NA Participants |
| AAB-003 1 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum decrease in supine DBP >=20 mm Hg | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting DBP <50 mm Hg | NA Participants |
| AAB-003 1 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting pulse rate <40 or >120 bpm | NA Participants |
| AAB-003 1 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine SBP <90 mm Hg | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum increase in supine SBP >=30 mm Hg | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum decrease in supine SBP >=30 mm Hg | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine DBP <50 mm Hg | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum increase in supine DBP >=20 mm Hg | 3 Participants |
| AAB-003 1 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine pulse rate <40 or >120 bpm | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting DBP <50 mm Hg | NA Participants |
| AAB-003 2 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum increase in supine SBP >=30 mm Hg | 3 Participants |
| AAB-003 2 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine SBP <90 mm Hg | 1 Participants |
| AAB-003 2 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine DBP <50 mm Hg | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting SBP <90 mm Hg | NA Participants |
| AAB-003 2 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum decrease in supine SBP >=30 mm Hg | 5 Participants |
| AAB-003 2 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine pulse rate <40 or >120 bpm | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum increase in supine DBP >=20 mm Hg | 4 Participants |
| AAB-003 2 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum decrease in supine DBP >=20 mm Hg | 4 Participants |
| AAB-003 2 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting pulse rate <40 or >120 bpm | NA Participants |
| AAB-003 4 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting SBP <90 mm Hg | NA Participants |
| AAB-003 4 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine SBP <90 mm Hg | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum decrease in supine DBP >=20 mm Hg | 1 Participants |
| AAB-003 4 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine DBP <50 mm Hg | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting DBP <50 mm Hg | NA Participants |
| AAB-003 4 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting pulse rate <40 or >120 bpm | NA Participants |
| AAB-003 4 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum increase in supine SBP >=30 mm Hg | 7 Participants |
| AAB-003 4 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum decrease in supine SBP >=30 mm Hg | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine pulse rate <40 or >120 bpm | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum increase in supine DBP >=20 mm Hg | 2 Participants |
| AAB-003 8 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine DBP <50 mm Hg | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting pulse rate <40 or >120 bpm | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum increase in supine DBP >=20 mm Hg | 5 Participants |
| AAB-003 8 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum increase in supine SBP >=30 mm Hg | 2 Participants |
| AAB-003 8 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine SBP <90 mm Hg | 1 Participants |
| AAB-003 8 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Supine pulse rate <40 or >120 bpm | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting DBP <50 mm Hg | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum decrease in supine SBP >=30 mm Hg | 4 Participants |
| AAB-003 8 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum decrease in supine DBP >=20 mm Hg | 4 Participants |
| AAB-003 8 mg/kg | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting SBP <90 mm Hg | 0 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting DBP <50 mm Hg | 0 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting pulse rate <40 or >120 bpm | 0 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Concern | Supine DBP <50 mm Hg | 1 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Concern | Supine pulse rate <40 or >120 bpm | 0 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum increase in supine SBP >=30 mm Hg | 6 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Concern | Sitting SBP <90 mm Hg | 0 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum decrease in supine SBP >=30 mm Hg | 8 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum increase in supine DBP >=20 mm Hg | 8 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Concern | Maximum decrease in supine DBP >=20 mm Hg | 8 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Concern | Supine SBP <90 mm Hg | 0 Participants |
Primary
Serum Decay Half-Life (t1/2) for AAB-003 at Day 1
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
Population: Evaluable participants in the PK analysis set (all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Serum Decay Half-Life (t1/2) for AAB-003 at Day 1 | 27.77 Days | Standard Deviation 6.988 |
| AAB-003 1 mg/kg | Serum Decay Half-Life (t1/2) for AAB-003 at Day 1 | 20.04 Days | Standard Deviation 8.921 |
| AAB-003 2 mg/kg | Serum Decay Half-Life (t1/2) for AAB-003 at Day 1 | 24.45 Days | Standard Deviation 4.8686 |
| AAB-003 4 mg/kg | Serum Decay Half-Life (t1/2) for AAB-003 at Day 1 | 21.10 Days | Standard Deviation 5.2 |
| AAB-003 8 mg/kg | Serum Decay Half-Life (t1/2) for AAB-003 at Day 1 | 22.89 Days | Standard Deviation 4.5086 |
Primary
Serum Decay Half-Life (t1/2) for AAB-003 at Week 26
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.
Population: Evaluable participants in the PK analysis set (all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Serum Decay Half-Life (t1/2) for AAB-003 at Week 26 | 23.41 Days | Standard Deviation 6.8638 |
| AAB-003 1 mg/kg | Serum Decay Half-Life (t1/2) for AAB-003 at Week 26 | 22.32 Days | Standard Deviation 3.1454 |
| AAB-003 2 mg/kg | Serum Decay Half-Life (t1/2) for AAB-003 at Week 26 | 22.83 Days | Standard Deviation 4.1356 |
| AAB-003 4 mg/kg | Serum Decay Half-Life (t1/2) for AAB-003 at Week 26 | 22.27 Days | Standard Deviation 3.2448 |
| AAB-003 8 mg/kg | Serum Decay Half-Life (t1/2) for AAB-003 at Week 26 | 22.81 Days | Standard Deviation 4.3455 |
Primary
Systemic Clearance (CL) for AAB-003 in Serum at Day 1
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
Population: Evaluable participants in the PK analysis set (all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Systemic Clearance (CL) for AAB-003 in Serum at Day 1 | 0.08934 milliliter/hour/kilogram (mL/hr/kg) | Geometric Coefficient of Variation 39 |
| AAB-003 1 mg/kg | Systemic Clearance (CL) for AAB-003 in Serum at Day 1 | 0.07657 milliliter/hour/kilogram (mL/hr/kg) | Geometric Coefficient of Variation 18 |
| AAB-003 2 mg/kg | Systemic Clearance (CL) for AAB-003 in Serum at Day 1 | 0.07914 milliliter/hour/kilogram (mL/hr/kg) | Geometric Coefficient of Variation 17 |
| AAB-003 4 mg/kg | Systemic Clearance (CL) for AAB-003 in Serum at Day 1 | 0.08615 milliliter/hour/kilogram (mL/hr/kg) | Geometric Coefficient of Variation 21 |
| AAB-003 8 mg/kg | Systemic Clearance (CL) for AAB-003 in Serum at Day 1 | 0.09739 milliliter/hour/kilogram (mL/hr/kg) | Geometric Coefficient of Variation 23 |
Primary
Systemic Clearance (CL) for AAB-003 in Serum at Week 26
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.
Population: Evaluable participants in the PK analysis set (all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Systemic Clearance (CL) for AAB-003 in Serum at Week 26 | 0.06665 mL/hr/kg | Geometric Coefficient of Variation 22 |
| AAB-003 1 mg/kg | Systemic Clearance (CL) for AAB-003 in Serum at Week 26 | 0.06385 mL/hr/kg | Geometric Coefficient of Variation 9 |
| AAB-003 2 mg/kg | Systemic Clearance (CL) for AAB-003 in Serum at Week 26 | 0.07289 mL/hr/kg | Geometric Coefficient of Variation 28 |
| AAB-003 4 mg/kg | Systemic Clearance (CL) for AAB-003 in Serum at Week 26 | 0.08133 mL/hr/kg | Geometric Coefficient of Variation 29 |
| AAB-003 8 mg/kg | Systemic Clearance (CL) for AAB-003 in Serum at Week 26 | 0.07943 mL/hr/kg | Geometric Coefficient of Variation 34 |
Primary
Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Day 1
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
Population: PK Analysis Set consisted of all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Day 1 | 1.92 Hours (hr) | Full Range 30 |
| AAB-003 1 mg/kg | Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Day 1 | 4.00 Hours (hr) | Full Range 33 |
| AAB-003 2 mg/kg | Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Day 1 | 1.54 Hours (hr) | Full Range 16 |
| AAB-003 4 mg/kg | Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Day 1 | 1.50 Hours (hr) | Full Range 20 |
| AAB-003 8 mg/kg | Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Day 1 | 3.02 Hours (hr) | Full Range 24 |
Primary
Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Week 26
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.
Population: Evaluable participants in the PK analysis set (all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Week 26 | 1.56 Hours (hr) | Full Range 22 |
| AAB-003 1 mg/kg | Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Week 26 | 2.00 Hours (hr) | Full Range 9 |
| AAB-003 2 mg/kg | Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Week 26 | 1.64 Hours (hr) | Full Range 28 |
| AAB-003 4 mg/kg | Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Week 26 | 2.00 Hours (hr) | Full Range 29 |
| AAB-003 8 mg/kg | Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Week 26 | 1.50 Hours (hr) | Full Range 34 |
Primary
Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Day 1
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
Population: Evaluable participants in the PK analysis set (all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Day 1 | 78.44 mL/kg | Geometric Coefficient of Variation 38 |
| AAB-003 1 mg/kg | Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Day 1 | 59.74 mL/kg | Geometric Coefficient of Variation 37 |
| AAB-003 2 mg/kg | Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Day 1 | 61.67 mL/kg | Geometric Coefficient of Variation 21 |
| AAB-003 4 mg/kg | Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Day 1 | 60.44 mL/kg | Geometric Coefficient of Variation 26 |
| AAB-003 8 mg/kg | Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Day 1 | 75.12 mL/kg | Geometric Coefficient of Variation 27 |
Primary
Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Week 26
Time frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.
Population: Evaluable participants in the PK analysis set (all randomized participants who received at least one infusion of study medication and have at least one post-dose PK parameter assessment).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Week 26 | 54.66 mL/kg | Geometric Coefficient of Variation 18 |
| AAB-003 1 mg/kg | Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Week 26 | 48.27 mL/kg | Geometric Coefficient of Variation 9 |
| AAB-003 2 mg/kg | Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Week 26 | 56.90 mL/kg | Geometric Coefficient of Variation 37 |
| AAB-003 4 mg/kg | Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Week 26 | 65.11 mL/kg | Geometric Coefficient of Variation 23 |
| AAB-003 8 mg/kg | Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Week 26 | 61.24 mL/kg | Geometric Coefficient of Variation 46 |
Other Pre-specified
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40
Time frame: Weeks 1, 3, 6, 10, 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39.
Population: All randomized participants who received at least one infusion of study medication, had a Baseline PD parameter assessment, and at least one post-dose PD parameter assessment. n = number of evaluable participants at the corresponding timeframe.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AAB-003 0.5 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 2647 ng*hr/mL | Geometric Coefficient of Variation 31 |
| AAB-003 0.5 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 2614 ng*hr/mL | Geometric Coefficient of Variation 32 |
| AAB-003 1 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 6057 ng*hr/mL | Geometric Coefficient of Variation 47 |
| AAB-003 1 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 4929 ng*hr/mL | Geometric Coefficient of Variation 37 |
| AAB-003 2 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 7854 ng*hr/mL | Geometric Coefficient of Variation 19 |
| AAB-003 2 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 6119 ng*hr/mL | Geometric Coefficient of Variation 31 |
| AAB-003 4 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 12940 ng*hr/mL | Geometric Coefficient of Variation 17 |
| AAB-003 4 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 11910 ng*hr/mL | Geometric Coefficient of Variation 26 |
| AAB-003 8 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 22820 ng*hr/mL | Geometric Coefficient of Variation 26 |
| AAB-003 8 mg/kg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 19740 ng*hr/mL | Geometric Coefficient of Variation 25 |
| Placebo | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 631.6 ng*hr/mL | Geometric Coefficient of Variation 23 |
| Placebo | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 798.8 ng*hr/mL | Geometric Coefficient of Variation 55 |
Other Pre-specified
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Amyloid-Beta x-40
Time frame: Baseline; Day 2 (24 hours post start of infusion); Weeks 1, 6, and 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39.
Population: All randomized participants who received at least one infusion of study medication, had a Baseline PD parameter assessment, at least one post-dose PD parameter assessment, and who had available data for AUCinf. No participants had available data for AUCinf in AAB-003 8 mg/kg and Placebo Groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Amyloid-Beta x-40 | 2916 ng*hr/mL | — |
| AAB-003 1 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Amyloid-Beta x-40 | 5463 ng*hr/mL | — |
| AAB-003 2 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Amyloid-Beta x-40 | 8965 ng*hr/mL | Geometric Coefficient of Variation 19 |
| AAB-003 4 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Amyloid-Beta x-40 | 12800 ng*hr/mL | Geometric Coefficient of Variation 1 |
Other Pre-specified
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Amyloid-Beta x-40
Time frame: Baseline; Day 2 (24 hours post start of infusion); Weeks 1, 6, and 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39.
Population: All randomized participants who received at least one infusion of study medication, had a Baseline PD parameter assessment, at least one post-dose PD parameter assessment, and who had available data for AUClast.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Amyloid-Beta x-40 | 2664 ng*hr/mL | Geometric Coefficient of Variation 31 |
| AAB-003 1 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Amyloid-Beta x-40 | 6041 ng*hr/mL | Geometric Coefficient of Variation 47 |
| AAB-003 2 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Amyloid-Beta x-40 | 7836 ng*hr/mL | Geometric Coefficient of Variation 19 |
| AAB-003 4 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Amyloid-Beta x-40 | 12970 ng*hr/mL | Geometric Coefficient of Variation 17 |
| AAB-003 8 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Amyloid-Beta x-40 | 22910 ng*hr/mL | Geometric Coefficient of Variation 25 |
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Amyloid-Beta x-40 | 639.7 ng*hr/mL | Geometric Coefficient of Variation 23 |
Other Pre-specified
Cerebrospinal Fluid (CSF) Concentration of AAB-003 at Week 32
Participants enrolled in the 2, 4 and 8 mg/kg cohorts participated in an optional CSF collection. Participants enrolled in the maximum tolerated dose (MTD) cohort were mandatorily collected for CSF.
Time frame: Week 32 or Early Withdrawal
Population: All randomized and treated participants in the 2, 4 and 8 mg/kg cohorts who consented to the collection of CSF samples.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Cerebrospinal Fluid (CSF) Concentration of AAB-003 at Week 32 | 15.220 nanogram/millliter (ng/mL) | — |
| AAB-003 1 mg/kg | Cerebrospinal Fluid (CSF) Concentration of AAB-003 at Week 32 | 45.020 nanogram/millliter (ng/mL) | — |
| AAB-003 2 mg/kg | Cerebrospinal Fluid (CSF) Concentration of AAB-003 at Week 32 | 79.160 nanogram/millliter (ng/mL) | Standard Deviation 53.0486 |
Other Pre-specified
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39
The ADAS-cog 70 Point is a structured scale (approximately 40 min to complete) that evaluates memory, orientation, attention, reasoning, language and constructional praxis. This study used the 11-item cognitive subscale of the ADAS-Cog with scores ranging from 0 to 70 points; higher scores indicated greater cognitive impairment.
Time frame: Baseline, Weeks 13, 26 and 39
Population: All participants who were randomized to a treatment and received at least one infusion of study medication. n = number of evaluable participants at the corresponding timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AAB-003 0.5 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,24,19) | 12.6 Units on a scale | Standard Deviation 3.73 |
| AAB-003 0.5 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 13 (n=6,5,15,15,22,19) | 1.3 Units on a scale | Standard Deviation 1.45 |
| AAB-003 0.5 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,13,18,19) | 0.9 Units on a scale | Standard Deviation 2.73 |
| AAB-003 0.5 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 39 (n=6,4,14,13,19,17) | 0.2 Units on a scale | Standard Deviation 3.13 |
| AAB-003 1 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,13,18,19) | 0.7 Units on a scale | Standard Deviation 4.73 |
| AAB-003 1 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 39 (n=6,4,14,13,19,17) | 1.4 Units on a scale | Standard Deviation 3.41 |
| AAB-003 1 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,24,19) | 20.4 Units on a scale | Standard Deviation 7.49 |
| AAB-003 1 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 13 (n=6,5,15,15,22,19) | 3.3 Units on a scale | Standard Deviation 4.39 |
| AAB-003 2 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,13,18,19) | 0.5 Units on a scale | Standard Deviation 5.4 |
| AAB-003 2 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 13 (n=6,5,15,15,22,19) | -0.4 Units on a scale | Standard Deviation 5.08 |
| AAB-003 2 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,24,19) | 21.6 Units on a scale | Standard Deviation 10.76 |
| AAB-003 2 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 39 (n=6,4,14,13,19,17) | 2.6 Units on a scale | Standard Deviation 6.8 |
| AAB-003 4 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,24,19) | 23.0 Units on a scale | Standard Deviation 11.15 |
| AAB-003 4 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 13 (n=6,5,15,15,22,19) | 3.2 Units on a scale | Standard Deviation 4.18 |
| AAB-003 4 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,13,18,19) | 3.3 Units on a scale | Standard Deviation 5.55 |
| AAB-003 4 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 39 (n=6,4,14,13,19,17) | 4.1 Units on a scale | Standard Deviation 9.8 |
| AAB-003 8 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,24,19) | 18.0 Units on a scale | Standard Deviation 7.28 |
| AAB-003 8 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 13 (n=6,5,15,15,22,19) | -1.2 Units on a scale | Standard Deviation 4.2 |
| AAB-003 8 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 39 (n=6,4,14,13,19,17) | -0.5 Units on a scale | Standard Deviation 5.88 |
| AAB-003 8 mg/kg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,13,18,19) | -0.8 Units on a scale | Standard Deviation 5.07 |
| Placebo | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,24,19) | 18.4 Units on a scale | Standard Deviation 7.54 |
| Placebo | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,13,18,19) | 1.4 Units on a scale | Standard Deviation 5.85 |
| Placebo | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 39 (n=6,4,14,13,19,17) | 1.4 Units on a scale | Standard Deviation 3.95 |
| Placebo | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 | Week 13 (n=6,5,15,15,22,19) | 0.2 Units on a scale | Standard Deviation 3.4 |
Other Pre-specified
Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39
The NPI is an instrument used to assess changes of behavior that have appeared in a defined period of time in participants with Alzheimer's disease (AD) and other dementias. Twelve (12) behavioral areas are assessed in the NPI - delusions, apathy, hallucinations, disinhibition, agitation, irritability, depression, aberrant motor behavior, anxiety, nighttime behaviors, euphoria, appetite, and eating changes. The NPI score is based on frequency and severity of specific behaviors within these categories as reported by the caregiver. A separate caregiver distress score may also be included. The NPI ranges from 0 to 144 (higher scores indicate greater psychopathology).
Time frame: Baseline, Weeks 13, 26 and 39
Population: All participants who were randomized to a treatment and received at least one infusion of study medication. n = number of evaluable participants at the corresponding timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AAB-003 0.5 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,14,18,19) | -1.7 Units on a scale | Standard Deviation 5.24 |
| AAB-003 0.5 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 13 (n=6,6,15,15,21,18) | -2.7 Units on a scale | Standard Deviation 4.8 |
| AAB-003 0.5 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,23,19) | 11.7 Units on a scale | Standard Deviation 9.67 |
| AAB-003 0.5 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 39 (n=6,3,14,13,19,17) | 0.5 Units on a scale | Standard Deviation 5.21 |
| AAB-003 1 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 39 (n=6,3,14,13,19,17) | 3.3 Units on a scale | Standard Deviation 2.52 |
| AAB-003 1 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,23,19) | 6.3 Units on a scale | Standard Deviation 9.18 |
| AAB-003 1 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,14,18,19) | 4.8 Units on a scale | Standard Deviation 4.09 |
| AAB-003 1 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 13 (n=6,6,15,15,21,18) | 4.8 Units on a scale | Standard Deviation 6.68 |
| AAB-003 2 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 13 (n=6,6,15,15,21,18) | -0.7 Units on a scale | Standard Deviation 4.27 |
| AAB-003 2 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,23,19) | 9.1 Units on a scale | Standard Deviation 8.69 |
| AAB-003 2 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,14,18,19) | -1.2 Units on a scale | Standard Deviation 2.94 |
| AAB-003 2 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 39 (n=6,3,14,13,19,17) | 0.6 Units on a scale | Standard Deviation 6.61 |
| AAB-003 4 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 13 (n=6,6,15,15,21,18) | 0.4 Units on a scale | Standard Deviation 7.31 |
| AAB-003 4 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 39 (n=6,3,14,13,19,17) | 4.8 Units on a scale | Standard Deviation 17.07 |
| AAB-003 4 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,14,18,19) | 4.6 Units on a scale | Standard Deviation 12.17 |
| AAB-003 4 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,23,19) | 10.8 Units on a scale | Standard Deviation 11.46 |
| AAB-003 8 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 13 (n=6,6,15,15,21,18) | 0.3 Units on a scale | Standard Deviation 4.94 |
| AAB-003 8 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,14,18,19) | 0.3 Units on a scale | Standard Deviation 6.01 |
| AAB-003 8 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,23,19) | 7.7 Units on a scale | Standard Deviation 7.3 |
| AAB-003 8 mg/kg | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 39 (n=6,3,14,13,19,17) | 0.1 Units on a scale | Standard Deviation 6.7 |
| Placebo | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,14,18,19) | -3.4 Units on a scale | Standard Deviation 8.65 |
| Placebo | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 39 (n=6,3,14,13,19,17) | -2.6 Units on a scale | Standard Deviation 10.63 |
| Placebo | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Week 13 (n=6,6,15,15,21,18) | -2.1 Units on a scale | Standard Deviation 6.81 |
| Placebo | Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,23,19) | 13.8 Units on a scale | Standard Deviation 12.93 |
Other Pre-specified
Change From Baseline in CSF Amyloid-beta x-40 Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups
Time frame: Baseline and Week 32
Population: The CSF analysis set consisted of participants in the AAB-003 8 mg/kg cohort who had provided sufficient CSF samples at Baseline and Week 32 to allow for assaying of both samples, and who had no occurrence of VE.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Change From Baseline in CSF Amyloid-beta x-40 Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups | 113.53 picogram/milliliter (pg/mL) | Standard Deviation 817.27 |
| AAB-003 1 mg/kg | Change From Baseline in CSF Amyloid-beta x-40 Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups | 348.64 picogram/milliliter (pg/mL) | Standard Deviation 1321.047 |
Comparison: Change from baseline, within groupp-value: 0.59980% CI: [-170.3, 397.35]t-test, 2 sided
Other Pre-specified
Change From Baseline in CSF Amyloid-beta x-42 Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups
Time frame: Baseline and Week 32
Population: The CSF analysis set consisted of participants in the AAB-003 8 mg/kg cohort who had provided sufficient CSF samples at Baseline and Week 32 to allow for assaying of both samples, and who had no occurrence of VE.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Change From Baseline in CSF Amyloid-beta x-42 Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups | 48.85 pg/mL | Standard Deviation 174.589 |
| AAB-003 1 mg/kg | Change From Baseline in CSF Amyloid-beta x-42 Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups | 24.04 pg/mL | Standard Deviation 173.61 |
Comparison: Change from baseline, within groupp-value: 0.29780% CI: [-11.79, 109.48]t-test, 2 sided
Other Pre-specified
Change From Baseline in CSF P-tau Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups
Time frame: Baseline and Week 32
Population: The CSF analysis set consisted of participants in the AAB-003 8 mg/kg cohort who had provided sufficient CSF samples at Baseline and Week 32 to allow for assaying of both samples, and who had no occurrence of VE.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Change From Baseline in CSF P-tau Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups | 1.23 pg/mL | Standard Deviation 8.986 |
| AAB-003 1 mg/kg | Change From Baseline in CSF P-tau Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups | 1.92 pg/mL | Standard Deviation 7.755 |
Comparison: Change from baseline, within groupp-value: 0.60380% CI: [-1.89, 4.35]t-test, 2 sided
Other Pre-specified
Change From Baseline in CSF Tau Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups
Time frame: Baseline and Week 32
Population: The CSF analysis set consisted of participants in the AAB-003 8 mg/kg cohort who had provided sufficient CSF samples at Baseline and Week 32 to allow for assaying of both samples, and who had no occurrence of VE.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Change From Baseline in CSF Tau Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups | -15.26 pg/mL | Standard Deviation 110.229 |
| AAB-003 1 mg/kg | Change From Baseline in CSF Tau Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups | 67.94 pg/mL | Standard Deviation 63.514 |
Comparison: Change from baseline, within groupp-value: 0.680% CI: [-53.54, 23.02]t-test, 2 sided
Other Pre-specified
Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39
The DAD is a functional assessment based on an interview with the caregiver that takes approximately 20 min to administer and it is comprised of 40 items, 17 related to self-care and 23 items involving instrumental activities of daily living. The DAD is scored from 0 to 100 (higher scores indicate better functioning).
Time frame: Baseline, Weeks 13, 26 and 39
Population: All participants who were randomized to a treatment and received at least one infusion of study medication. n = number of evaluable participants at the corresponding timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AAB-003 0.5 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,24,19) | 84.5 Units on a scale | Standard Deviation 11.27 |
| AAB-003 0.5 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 13 (n=6,6,15,16,22,19) | 5.7 Units on a scale | Standard Deviation 8.82 |
| AAB-003 0.5 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,14,18,19) | 4.3 Units on a scale | Standard Deviation 9.2 |
| AAB-003 0.5 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 39 (n=6,4,14,14,19,17) | -1.8 Units on a scale | Standard Deviation 8.4 |
| AAB-003 1 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,24,19) | 63.7 Units on a scale | Standard Deviation 31.89 |
| AAB-003 1 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,14,18,19) | -0.8 Units on a scale | Standard Deviation 12.3 |
| AAB-003 1 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 13 (n=6,6,15,16,22,19) | -1.2 Units on a scale | Standard Deviation 14.22 |
| AAB-003 1 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 39 (n=6,4,14,14,19,17) | 0.5 Units on a scale | Standard Deviation 12.92 |
| AAB-003 2 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,14,18,19) | -3.8 Units on a scale | Standard Deviation 10.2 |
| AAB-003 2 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 13 (n=6,6,15,16,22,19) | -3.8 Units on a scale | Standard Deviation 11.61 |
| AAB-003 2 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,24,19) | 78.6 Units on a scale | Standard Deviation 20.84 |
| AAB-003 2 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 39 (n=6,4,14,14,19,17) | -6.9 Units on a scale | Standard Deviation 11.33 |
| AAB-003 4 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,14,18,19) | -10.4 Units on a scale | Standard Deviation 14.93 |
| AAB-003 4 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 13 (n=6,6,15,16,22,19) | -5.1 Units on a scale | Standard Deviation 15.57 |
| AAB-003 4 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,24,19) | 77.9 Units on a scale | Standard Deviation 17.91 |
| AAB-003 4 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 39 (n=6,4,14,14,19,17) | -14.6 Units on a scale | Standard Deviation 19.52 |
| AAB-003 8 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 39 (n=6,4,14,14,19,17) | -1.9 Units on a scale | Standard Deviation 12.39 |
| AAB-003 8 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 13 (n=6,6,15,16,22,19) | -6.3 Units on a scale | Standard Deviation 12.71 |
| AAB-003 8 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,24,19) | 84.8 Units on a scale | Standard Deviation 15.31 |
| AAB-003 8 mg/kg | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,14,18,19) | 0.2 Units on a scale | Standard Deviation 14.32 |
| Placebo | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 26 (n=6,5,14,14,18,19) | -2.5 Units on a scale | Standard Deviation 7.73 |
| Placebo | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 39 (n=6,4,14,14,19,17) | -1.8 Units on a scale | Standard Deviation 11.31 |
| Placebo | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Week 13 (n=6,6,15,16,22,19) | -3.0 Units on a scale | Standard Deviation 7.56 |
| Placebo | Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 | Baseline (n=6,6,16,17,24,19) | 84.9 Units on a scale | Standard Deviation 12.65 |
Other Pre-specified
Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39
The CDR scale is a clinician-rated dementia staging instrument that tracks the progression of cognitive impairment in the following 6 categories - memory, orientation, judgment and problem solving, involvement in community affairs, home and hobbies, and personal care based on the CDR interview. The CDR is based on discussions between the clinician with the participant and caregiver using a structured format. A global CDR score is established by clinical scoring rules with values of 0 (no dementia), 0.5 (questionable dementia), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia). A more quantitative version of the CDR scale is obtained by summing up the ratings in each of the 6 categories to provide the (CDR-SB). The CDR-SB scale ranges from 0 to 18 where higher score indicates severe dementia.
Time frame: Baseline, Weeks 26 and 39
Population: All participants who were randomized to a treatment and received at least one infusion of study medication. n = number of evaluable participants at the corresponding timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AAB-003 0.5 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDR-SB - Week 26 (n=6,5,14,14,18,19) | 1.33 Units on a scale | Standard Deviation 1.751 |
| AAB-003 0.5 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Week 39 (n=6,4,14,14,19,17) | 0.33 Units on a scale | Standard Deviation 0.408 |
| AAB-003 0.5 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDR-SB - Week 39 (n=6,4,14,14,19,17) | 1.00 Units on a scale | Standard Deviation 3.286 |
| AAB-003 0.5 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDS-SB - Baseline (n=6,6,16,17,24,19) | 8.00 Units on a scale | Standard Deviation 1.673 |
| AAB-003 0.5 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Baseline (n=6,6,16,17,24,19) | 0.67 Units on a scale | Standard Deviation 0.258 |
| AAB-003 0.5 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Week 26 (n=6,5,14,14,18,19) | 0.33 Units on a scale | Standard Deviation 0.408 |
| AAB-003 1 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Week 26 (n=6,5,14,14,18,19) | 0.30 Units on a scale | Standard Deviation 0.447 |
| AAB-003 1 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDR-SB - Week 39 (n=6,4,14,14,19,17) | 1.75 Units on a scale | Standard Deviation 1.708 |
| AAB-003 1 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDR-SB - Week 26 (n=6,5,14,14,18,19) | 1.40 Units on a scale | Standard Deviation 1.517 |
| AAB-003 1 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDS-SB - Baseline (n=6,6,16,17,24,19) | 11.17 Units on a scale | Standard Deviation 4.07 |
| AAB-003 1 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Week 39 (n=6,4,14,14,19,17) | 0.13 Units on a scale | Standard Deviation 0.25 |
| AAB-003 1 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Baseline (n=6,6,16,17,24,19) | 1.08 Units on a scale | Standard Deviation 0.492 |
| AAB-003 2 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDR-SB - Week 26 (n=6,5,14,14,18,19) | -0.07 Units on a scale | Standard Deviation 2.056 |
| AAB-003 2 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Week 39 (n=6,4,14,14,19,17) | 0.04 Units on a scale | Standard Deviation 0.414 |
| AAB-003 2 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Baseline (n=6,6,16,17,24,19) | 1.03 Units on a scale | Standard Deviation 0.618 |
| AAB-003 2 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDS-SB - Baseline (n=6,6,16,17,24,19) | 9.50 Units on a scale | Standard Deviation 4.351 |
| AAB-003 2 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Week 26 (n=6,5,14,14,18,19) | 0.04 Units on a scale | Standard Deviation 0.414 |
| AAB-003 2 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDR-SB - Week 39 (n=6,4,14,14,19,17) | 1.00 Units on a scale | Standard Deviation 2.449 |
| AAB-003 4 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDS-SB - Baseline (n=6,6,16,17,24,19) | 10.94 Units on a scale | Standard Deviation 3.614 |
| AAB-003 4 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Week 26 (n=6,5,14,14,18,19) | 0.25 Units on a scale | Standard Deviation 0.51 |
| AAB-003 4 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Week 39 (n=6,4,14,14,19,17) | 0.50 Units on a scale | Standard Deviation 0.679 |
| AAB-003 4 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDR-SB - Week 39 (n=6,4,14,14,19,17) | 1.86 Units on a scale | Standard Deviation 3.371 |
| AAB-003 4 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDR-SB - Week 26 (n=6,5,14,14,18,19) | 1.29 Units on a scale | Standard Deviation 2.758 |
| AAB-003 4 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Baseline (n=6,6,16,17,24,19) | 1.09 Units on a scale | Standard Deviation 0.476 |
| AAB-003 8 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDR-SB - Week 26 (n=6,5,14,14,18,19) | 0.17 Units on a scale | Standard Deviation 1.855 |
| AAB-003 8 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDS-SB - Baseline (n=6,6,16,17,24,19) | 8.75 Units on a scale | Standard Deviation 3.566 |
| AAB-003 8 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDR-SB - Week 39 (n=6,4,14,14,19,17) | 0.79 Units on a scale | Standard Deviation 2.84 |
| AAB-003 8 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Week 26 (n=6,5,14,14,18,19) | 0.03 Units on a scale | Standard Deviation 0.32 |
| AAB-003 8 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Week 39 (n=6,4,14,14,19,17) | 0.13 Units on a scale | Standard Deviation 0.436 |
| AAB-003 8 mg/kg | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Baseline (n=6,6,16,17,24,19) | 0.85 Units on a scale | Standard Deviation 0.429 |
| Placebo | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Week 39 (n=6,4,14,14,19,17) | -0.06 Units on a scale | Standard Deviation 0.3 |
| Placebo | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDS-SB - Baseline (n=6,6,16,17,24,19) | 8.89 Units on a scale | Standard Deviation 3.381 |
| Placebo | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Baseline (n=6,6,16,17,24,19) | 0.87 Units on a scale | Standard Deviation 0.467 |
| Placebo | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDR-SB - Week 26 (n=6,5,14,14,18,19) | 0.16 Units on a scale | Standard Deviation 1.979 |
| Placebo | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | Global CDR - Week 26 (n=6,5,14,14,18,19) | -0.03 Units on a scale | Standard Deviation 0.262 |
| Placebo | Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 | CDR-SB - Week 39 (n=6,4,14,14,19,17) | -0.35 Units on a scale | Standard Deviation 1.935 |
Other Pre-specified
Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39
The MMSE is a brief 30-point questionnaire test that is used to assess cognition. It is commonly used to screen for dementia. In the time span of about 10 min, it samples various functions, including arithmetic, memory and orientation. Scores range from 0 to 30 (higher scores indicate less impairment) and participants with scores of 16 to 26 were eligible.
Time frame: Baseline, Weeks 13, 26 and 39
Population: All participants who were randomized to a treatment and received at least one infusion of study medication. n = number of evaluable participants at the corresponding timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AAB-003 0.5 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Baseline (n=6,6,16,17,24,19) | 22.7 Units on a scale | Standard Deviation 1.37 |
| AAB-003 0.5 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 13 (n=6,6,15,16,22,19) | 1.8 Units on a scale | Standard Deviation 2.32 |
| AAB-003 0.5 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 26 (n=6,5,14,14,18,19) | 1.8 Units on a scale | Standard Deviation 1.72 |
| AAB-003 0.5 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 39 (n=6,4,14,14,19,17) | 1.5 Units on a scale | Standard Deviation 4.18 |
| AAB-003 1 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 26 (n=6,5,14,14,18,19) | 0.2 Units on a scale | Standard Deviation 1.1 |
| AAB-003 1 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 13 (n=6,6,15,16,22,19) | -0.5 Units on a scale | Standard Deviation 2.35 |
| AAB-003 1 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Baseline (n=6,6,16,17,24,19) | 22.5 Units on a scale | Standard Deviation 2.43 |
| AAB-003 1 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 39 (n=6,4,14,14,19,17) | -1.0 Units on a scale | Standard Deviation 0.82 |
| AAB-003 2 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 39 (n=6,4,14,14,19,17) | -0.2 Units on a scale | Standard Deviation 2.58 |
| AAB-003 2 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 26 (n=6,5,14,14,18,19) | 0.0 Units on a scale | Standard Deviation 3.51 |
| AAB-003 2 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 13 (n=6,6,15,16,22,19) | 0.1 Units on a scale | Standard Deviation 2.45 |
| AAB-003 2 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Baseline (n=6,6,16,17,24,19) | 20.8 Units on a scale | Standard Deviation 3.71 |
| AAB-003 4 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Baseline (n=6,6,16,17,24,19) | 20.1 Units on a scale | Standard Deviation 3 |
| AAB-003 4 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 39 (n=6,4,14,14,19,17) | -2.2 Units on a scale | Standard Deviation 4.56 |
| AAB-003 4 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 13 (n=6,6,15,16,22,19) | -1.4 Units on a scale | Standard Deviation 2.78 |
| AAB-003 4 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 26 (n=6,5,14,14,18,19) | -2.0 Units on a scale | Standard Deviation 2.96 |
| AAB-003 8 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 26 (n=6,5,14,14,18,19) | 1.6 Units on a scale | Standard Deviation 2.91 |
| AAB-003 8 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 39 (n=6,4,14,14,19,17) | 1.4 Units on a scale | Standard Deviation 3.55 |
| AAB-003 8 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 13 (n=6,6,15,16,22,19) | 0.9 Units on a scale | Standard Deviation 2 |
| AAB-003 8 mg/kg | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Baseline (n=6,6,16,17,24,19) | 21.2 Units on a scale | Standard Deviation 2.82 |
| Placebo | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 13 (n=6,6,15,16,22,19) | 1.0 Units on a scale | Standard Deviation 1.6 |
| Placebo | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 26 (n=6,5,14,14,18,19) | 0.7 Units on a scale | Standard Deviation 2.91 |
| Placebo | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Week 39 (n=6,4,14,14,19,17) | 0.5 Units on a scale | Standard Deviation 3.06 |
| Placebo | Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 | Baseline (n=6,6,16,17,24,19) | 21.2 Units on a scale | Standard Deviation 3.78 |
Other Pre-specified
CSF Amyloid-beta x-40 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups
Time frame: Baseline and Week 32
Population: The CSF analysis set consisted of participants in the AAB-003 8 mg/kg cohort who had provided sufficient CSF samples at Baseline and Week 32 to allow for assaying of both samples, and who had no occurrence of VE.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| AAB-003 0.5 mg/kg | CSF Amyloid-beta x-40 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Baseline | 5685.4 picogram/milliliter (pg/mL) |
| AAB-003 0.5 mg/kg | CSF Amyloid-beta x-40 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Week 32 | 5836.1 picogram/milliliter (pg/mL) |
| AAB-003 1 mg/kg | CSF Amyloid-beta x-40 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Baseline | 7413.6 picogram/milliliter (pg/mL) |
| AAB-003 1 mg/kg | CSF Amyloid-beta x-40 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Week 32 | 8883.2 picogram/milliliter (pg/mL) |
Other Pre-specified
CSF Amyloid-beta x-42 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups
Time frame: Baseline and Week 32
Population: The CSF analysis set consisted of participants in the AAB-003 8 mg/kg cohort who had provided sufficient CSF samples at Baseline and Week 32 to allow for assaying of both samples, and who had no occurrence of VE.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| AAB-003 0.5 mg/kg | CSF Amyloid-beta x-42 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Baseline | 485.6 pg/mL |
| AAB-003 0.5 mg/kg | CSF Amyloid-beta x-42 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Week 32 | 343.3 pg/mL |
| AAB-003 1 mg/kg | CSF Amyloid-beta x-42 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Baseline | 217.2 pg/mL |
| AAB-003 1 mg/kg | CSF Amyloid-beta x-42 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Week 32 | 331 pg/mL |
Other Pre-specified
CSF P-tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups
Time frame: Baseline and Week 32
Population: The CSF analysis set consisted of participants in the AAB-003 8 mg/kg cohort who had provided sufficient CSF samples at Baseline and Week 32 to allow for assaying of both samples, and who had no occurrence of VE.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| AAB-003 0.5 mg/kg | CSF P-tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Baseline | 89 pg/mL |
| AAB-003 0.5 mg/kg | CSF P-tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Week 32 | 100.3 pg/mL |
| AAB-003 1 mg/kg | CSF P-tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Baseline | 122.7 pg/mL |
| AAB-003 1 mg/kg | CSF P-tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Week 32 | 140.5 pg/mL |
Other Pre-specified
CSF Tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups
Time frame: Baseline and Week 32
Population: The CSF analysis set consisted of participants in the AAB-003 8 mg/kg cohort who had provided sufficient CSF samples at Baseline and Week 32 to allow for assaying of both samples, and who had no occurrence of VE.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| AAB-003 0.5 mg/kg | CSF Tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Baseline | 659.6 pg/mL |
| AAB-003 0.5 mg/kg | CSF Tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Week 32 | 739.4 pg/mL |
| AAB-003 1 mg/kg | CSF Tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Baseline | 856.1 pg/mL |
| AAB-003 1 mg/kg | CSF Tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups | Week 32 | 1115.6 pg/mL |
Other Pre-specified
Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40
Time frame: Weeks 1, 3, 6, 10, 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39.
Population: All randomized participants who received at least one infusion of study medication and have at least one postdose pharmacodynamic (PD) parameter assessment. n = number of evaluable participants at the corresponding timeframe.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AAB-003 0.5 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 3.321 ng/mL | Geometric Coefficient of Variation 50 |
| AAB-003 0.5 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 1.964 ng/mL | Geometric Coefficient of Variation 35 |
| AAB-003 1 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 6.959 ng/mL | Geometric Coefficient of Variation 29 |
| AAB-003 1 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 3.805 ng/mL | Geometric Coefficient of Variation 31 |
| AAB-003 2 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 8.202 ng/mL | Geometric Coefficient of Variation 19 |
| AAB-003 2 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 3.804 ng/mL | Geometric Coefficient of Variation 23 |
| AAB-003 4 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 11.89 ng/mL | Geometric Coefficient of Variation 10 |
| AAB-003 4 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 7.537 ng/mL | Geometric Coefficient of Variation 26 |
| AAB-003 8 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 18.03 ng/mL | Geometric Coefficient of Variation 19 |
| AAB-003 8 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 12.25 ng/mL | Geometric Coefficient of Variation 20 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 0.3511 ng/mL | Geometric Coefficient of Variation 25 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 0.4689 ng/mL | Geometric Coefficient of Variation 84 |
Other Pre-specified
Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum
Human serum anti-drug antibodies (ADA) samples were analyzed for the presence or absence of anti-AAB-003 antibodies by enzyme-linked immunosorbent assay (ELISA) method
Time frame: Day 1 (predose), Week 13 (predose), Week 26 (predose) and Week 39 or Early Withdrawal
Population: All participants who received an infusion of study medication. n = number of evaluable participants at the corresponding timeframe.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 39 (n=6,4,14,14,19,16) | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 13 (n=6,5,15,16,22,19) | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Day 1 (n=6,6,16,17,24,19) | 0 Participants |
| AAB-003 0.5 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 26 (n=6,5,14,14,17,18) | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 26 (n=6,5,14,14,17,18) | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Day 1 (n=6,6,16,17,24,19) | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 13 (n=6,5,15,16,22,19) | 0 Participants |
| AAB-003 1 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 39 (n=6,4,14,14,19,16) | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 13 (n=6,5,15,16,22,19) | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 26 (n=6,5,14,14,17,18) | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Day 1 (n=6,6,16,17,24,19) | 0 Participants |
| AAB-003 2 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 39 (n=6,4,14,14,19,16) | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 26 (n=6,5,14,14,17,18) | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Day 1 (n=6,6,16,17,24,19) | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 13 (n=6,5,15,16,22,19) | 0 Participants |
| AAB-003 4 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 39 (n=6,4,14,14,19,16) | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Day 1 (n=6,6,16,17,24,19) | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 26 (n=6,5,14,14,17,18) | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 39 (n=6,4,14,14,19,16) | 0 Participants |
| AAB-003 8 mg/kg | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 13 (n=6,5,15,16,22,19) | 0 Participants |
| Placebo | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Day 1 (n=6,6,16,17,24,19) | 0 Participants |
| Placebo | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 13 (n=6,5,15,16,22,19) | 0 Participants |
| Placebo | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 39 (n=6,4,14,14,19,16) | 0 Participants |
| Placebo | Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum | Week 26 (n=6,5,14,14,17,18) | 0 Participants |
Other Pre-specified
Plasma Decay Half-Life (t1/2) for Amyloid-Beta x-40
Time frame: Baseline; Day 2 (24 hours post start of infusion); Weeks 1, 6, and 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39.
Population: All randomized participants who received at least one infusion of study medication, had a Baseline PD parameter assessment, at least one post-dose PD parameter assessment, and who had available data for t1/2. No participants had available data for t1/2 in AAB-003 8 mg/kg and Placebo Groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AAB-003 0.5 mg/kg | Plasma Decay Half-Life (t1/2) for Amyloid-Beta x-40 | 26.57 Day | — |
| AAB-003 1 mg/kg | Plasma Decay Half-Life (t1/2) for Amyloid-Beta x-40 | 32.14 Day | — |
| AAB-003 2 mg/kg | Plasma Decay Half-Life (t1/2) for Amyloid-Beta x-40 | 30.71 Day | Standard Deviation 3.2303 |
| AAB-003 4 mg/kg | Plasma Decay Half-Life (t1/2) for Amyloid-Beta x-40 | 29.41 Day | Standard Deviation 5.7374 |
Other Pre-specified
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40
Time frame: Weeks 1, 3, 6, 10, 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39.
Population: All randomized participants who received at least one infusion of study medication, had a Baseline PD parameter assessment and at least one post-dose PD parameter assessment. n = number of evaluable participants at the corresponding timeframe.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| AAB-003 0.5 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 24.2 Hours | Full Range 50 |
| AAB-003 0.5 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 2.03 Hours | Full Range 35 |
| AAB-003 1 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 24.0 Hours | Full Range 29 |
| AAB-003 1 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 2.00 Hours | Full Range 31 |
| AAB-003 2 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 983 Hours | Full Range 23 |
| AAB-003 2 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 24.0 Hours | Full Range 19 |
| AAB-003 4 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 166 Hours | Full Range 10 |
| AAB-003 4 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 1010 Hours | Full Range 26 |
| AAB-003 8 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 164 Hours | Full Range 19 |
| AAB-003 8 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 1010 Hours | Full Range 20 |
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40 | Week 26 - Week 39 (n=5,4,14,14,17,14) | 1030 Hours | Full Range 84 |
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40 | Week 1 - Week 13 (n=6,5,14,16,22,19) | 168 Hours | Full Range 25 |