compared with placebo. The secondary objective was
to look at the pharmacokinetic profile following IV
and subcutaneous doses. Study participants included
healthy volunteers ages 18 to 80 and patients with
probable Alzheimer’s disease. Patients with Alzheimer’s disease were between ages 50 and 80 and had a
Mini-Mental State Examination score of 16 to 28; a
Clinical Dementia Rating global score of 0.5, 1.0, or
2.0; and 18F-florbetapir PET scan evidence of cerebral amyloid pathology.
In the single-dose escalation phase, six cohorts of
eight healthy volunteers each received IV doses that
ranged from 225 mg to 16,800 mg. Another cohort
received 1,200 mg of the drug subcutaneously. In the
multiple-dose phase, a cohort of healthy volunteers and
a cohort of patients with mild-to-moderate Alzheimer’s
disease received four weekly doses of 8. 4 g.
“The drug was well tolerated, even at these high
doses,” Dr. Kerchner said. “So far, there have been
no dose-limiting adverse events, no serious adverse
events, no deaths, and no one who stopped the drug
due to adverse events.” In the single-dose cohorts, adverse events that occurred in more than one participant
included headache, infusion/injection site reaction,
upper respiratory tract infection, nausea, vomiting,
and gastrointestinal viral infection. In the multiple-dose cohorts, adverse events that occurred in more
than one participant included vessel puncture site
complications and postural dizziness.
ABBV-8E12 for PSP and Alzheimer’s Disease
Kumar Budur, MD, of AbbVie, Chicago, presented the
results of a phase I study of ABBV-8E12, a humanized anti-tau monoclonal antibody, in patients with
progressive supranuclear palsy (PSP). He also gave an
overview of two ongoing phase II studies of ABBV-
8E12 for early Alzheimer’s disease and PSP.
“PSP is a chronic progressive neurodegenerative
disorder that affects movement, control of gait and
balance, speech, swallowing, vision, mood and behavior, and thinking,” Dr.
Budur explained. “The time
from the onset of symptoms
to death is only seven years.
There currently are no approved treatments for this
condition.” PSP affects approximately 20,000 people in the United States, and
symptoms typically begin after age 60.
The phase I trial in patients with PSP was a double-blind, placebo-controlled, single ascending dose study
assessing the drug’s safety, tolerability, pharmacokinetics, and immunogenicity. Investigators randomized 30
participants to a single IV infusion of ABBV-8E12 ( 2. 5,
7.5, 15, 25, or 50 mg/kg) or placebo in blocks of four
subjects, with one subject in each block randomized
to placebo and three to an active ABBV-8E12 dose. Researchers monitored safety and pharmacokinetics for 84
days post dosing.
Twenty-three patients received ABBV-8E12, and
seven patients received placebo. At baseline, subjects’
mean age was 68.8; 16 (53%) were men. Patients had to
be able to walk with minimal assistance to be included
in the study. Twenty-seven subjects completed the 84-
day follow-up and one subject ( 3.3%) withdrew from
the study due to an adverse event.
Twenty-one subjects experienced an adverse event,
including dermatitis (n = 5) and fall (n = 5). Three participants experienced serious adverse events. One patient had a subdural hematoma following two falls, one
had agitation/anxiety/perseverative behavior, and one
had hypertension. The serious adverse events occurred
in the 15, 25, and 50 mg/kg cohorts, respectively. AB-
BV-8E12 exhibited an acceptable safety and tolerability
profile to support repeat-dose testing in subjects with
tauopathies, Dr. Budur said.
Dr. Budur and colleagues are recruiting subjects for a multinational phase II study evaluating
ABBV-8E12 to delay the progression of Alzheimer’s
disease. Eligible subjects (n = 400) will meet criteria
for early Alzheimer’s disease and have a positive amyloid PET scan. “Subjects will be randomized to three
doses of ABBV-8E12 versus placebo, 100 subjects per
arm,” he said. In addition, investigators are recruiting
Humanized Anti-Tau Monoclonal
Antibody May Block the
Cell-to-Cell Spread of Tau
Geoffrey A. Kerchner,
Tau is a compelling target in