Research study testing the safety and tolerability of the investigationaldrug, BMS-708163, compared to placebo (inactive substance) in subjectswith prodromal Alzheimer's Disease
- Conditions
- ALZHEIMER DISEASEMedDRA version: 15.1Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2009-010067-16-SE
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 540
1) Signed Written Informed Consent
a) Patients (or legally acceptable representative as required by the IRB/IEC) &
their study partners have provided a written signed informed consent form/forms
(IRB/EC specific) prior to the initiation of any protocol required procedures;
b) For sites participating in intensive PK testing an additional signed written consent
by the patients & their study partners has been obtained prior to the initiation of
any intensive PK testing
2) Target Population
a) Patient meets prodromal Alzheimer’s disease criteria as defined by
i) Memory complaint by subject or study partner that is verified by a study
partner
ii) Abnormal memory function documented by at least 1 of the 4 following
criteria:
(1) scoring below the education adjusted cutoff on the Logical Memory II
subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale –
Revised (the maximum score is 25):
(a) less than or equal to 8 for 16 or more years of education.
(b) less than or equal to 4 for 8 - 15 years of education.
(c) less than or equal to 2 for 0 - 7 years of education. OR
(2) Free and Cued Selective Reminding Test (FCSRT) Total Recall score of = 39 OR
(3) FCSRT Free Recall score of = 24 OR
(4) FCSRT Delayed Free Recall score of = 8.
b) CSF Aß42 levels below 200 pg/mL or Total Tau / Aß42 ratio of = 0.39.
Additionally, patients who meet all other inclusion/exclusion criteria with the
exception of the CSF criteria above, may be eligible to be followed in a nonrandomized,observational cohort to
assess progression rates [see Section
6.4.4.8]);
c) Mini-Mental State Exam score between 24 and 30 (inclusive);
d) Clinical Dementia Rating global score must be = 0.5 at Screening and Baseline
and the Memory Box score must be at least 0.5 at both Screening and Baseline;
e) Patients must have an MRI performed during the screening period, prior to
randomization, to allow the results to be available at the baseline visit. Results
will be centrally read. To be eligible for the study the MRI results must:
i) Be normal (commensurate with age) or demonstrate atrophy consistent with
an Alzheimer’s disease diagnosis;
ii) Reveal no more than mild to moderate white matter disease;
iii) Up to 2 lacunar infarcts are acceptable however, no lacunes are permitted in
the anterior thalamus, genu of internal capsule, or basal forebrain;
iv) Reveal no cortical infarcts;
v) Reveal no more than four microbleeds. Note: if an MRI scanner with a field
strength > 1.5 T is used, a higher number of microbleeds will be acceptable
as determined by the central neuroradiologist.
vi) Reveal no single area of superficial siderosis (as defined by signal void
along the brain pial on GRE studies);
vii)Reveal no focal asymmetric lobar atrophy or other findings suggesting that the
primary cause of dementia is better attributed to a cause other than AD;
viii) Reveal no current or prior evidence of macrohemorrhages (> 10 mm);
f) Patient has a score of = 4 on the Modified Hachinski Scale (MHIS) at screening;
g) Patient is not currently being treated with approved marketed medications for AD
or if currently being treated is required to be on stable dose for at least 3 months
prior to Baseline & the study physician does not anticipate any modifications
during the study;
h) Patients that are not going to be maintained on approved marketed medications
for AD should be free of such medications for at least 3 months prior to Baseline
with no p
1)Sex & Reproductive Status
a)WOCBP
For purposes of this study, WOCBP include any female who has experienced
menarche & who is not postmenopausal. Post menopause is defined as
• Amenorrhea = 12 consecutive months without another cause or
• For women with irregular menstrual periods & on hormone replacement
therapy, a documented serum follicle stimulating hormone level
Women who are using oral contraceptives, other hormonal contraceptives (vaginal
products, skin patches, or implanted or injectable products), or mechanical
products such as an intrauterine device or barrier methods (diaphragm, condoms,
spermicides) to prevent pregnancy, or are practicing abstinence or where their
partner is sterile (eg, vasectomy) should be considered to be of childbearing
potential
b)pregnant or breastfeeding Women
c)Women with a + pregnancy test on enrollment or prior to administration of
investigational product
d)Sexually active fertile men not using effective birth control if their partners are
WOCBP
2)Target Disease Exceptions
a)Patient’s diagnosed with Dementia per DSM-IV criteria
b)Patients with any other medical condition other than prodromal Alzheimer’s
disease that could explain the patients memory or cognitive deficits (eg, Vitamin
B12 or folate deficiency, abnormal thyroid function, posttraumatic conditions,
syphilis, multiple sclerosis or another disorder of neuro-inflammation,
Parkinson’s disease, vascular or multi-infarct dementia, Huntington’s disease,
normal pressure hydrocephalus, CNS tumor, progressive supranuclear palsy,
seizure disorder (other than childhood febrile seizures), subdural hematoma).
3)Medical History & Concurrent Diseases
a)Patients w/ a history of stroke (Note: Patients w/ history of TIA may be
enrolled, if occurred at least 3 months prior to screening & they are
prescribed appropriate treatment (eg, platelet aggregation inhibitors)
b)Patient who are immunocompromised at screening including taking medications
that are systemic immunosuppressive treatment such as oral corticosteroids;
c)Patients w/ a history of gastrointestinal illnesses including:
i)a current diagnosis of active, peptic ulceration or gastrointestinal bleeding
within the last year &/or chronic inflammatory bowel disease, at screening
ii)a history of any gastrointestinal surgery that could impact upon the absorption
of study drug
iii)a + Fecal Immunochemical Test during the Screening period;
(unless subsequent upper & lower GI workup is negative for GI pathology);
iv)chronic or frequent episodes of loose stools
d)Patients w/ a Vitamin B12 or folate deficiency (Patients w/ a B12
deficiency may participate in the study if they are on stable Vitamin B12
replacement for at least 3 months prior to screening & their B12 levels are
within normal limits prior to randomization.
e)Patients w/ a Geriatric Depression Scale score of = 6 at screening.
f)Patient w/ any unstable cardiovascular (includes uncontrolled hypertension),
pulmonary, gastrointestinal or hepatic disease within 30 days prior to screening;
g)Patients who have been treated for or have had a diagnosis of schizophrenia or
Bipolar Disorder within 3 years, prior to screening;
h)Patients who have had an active major depressive episode within 6 months prior
to screening;
i)Patients w/ a history of neurosyphilis (indicated by a positive RPR test &
confirmed by a positive FTA-ABS test).
j)Patients having a history of drug or alcohol abuse within 12 months
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the long term safety and tolerability of BMS-708163 in patients with prodromal Alzheimer’s Disease.;Secondary Objective: To assess the predictive value of CSF biomarkers (Aß40, and Aß42, total Tau,<br>phosphorylated Tau) on progression to dementia.;Primary end point(s): The primary endpoint of this study is safety and tolerability.;Timepoint(s) of evaluation of this end point: During the treatment phase, every 2 weeks for the first 8 weeks, then monthly for the next 16 weeks and then every 12 weeks for the remainder of the study. In addition avagacestat treated patients will be seen for safety visits at 4 and 12 weeks post treatment, and will have a 24 week post treatment skin examination by a dermatologist.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): To assess the predictive value of CSF biomarkers (Aß40, and Aß42, total Tau, total Tau/Aß42 ratio, phosphorylated Tau) on progression to dementia;Timepoint(s) of evaluation of this end point: CSF Biomarkers will be assessed at Baseline, Week 2 (optional) Week 24 and Week 104. Progression to dementia will be assessed on an ongoing basis at all scheduled visits