| Eligibility |
Inclusion Criteria:
- Any gender over and including 50 years old.
- Willing and able to provide informed consent.
- Clinical Dementia Rating (Scale) (CDR) Global Score = 0.5.
- Self and/or study partner report and impairment on objective cognitive tasks
(performance on Hopkin's verbal learning task-revised (HVLT-R) - delay recall and/or
free recall > 1 standard deviation (SD) below mean for age/education level).
- Study Partner available, that spends at least 4 hours per week with the participant.
The Study Partner must be willing and able to assist with the CDR interview, and will
be provided with their own Information Sheet and Informed Consent form.
- Able to read and write in English and with minimum 7 years of formal education.
- Be considered eligible according to the following Tuberculosis (TB) screening
criteria:
1. Have no history of latent or active TB at screening. An exception is made for
participants who have a history of latent TB (defined for the purpose of this
study as having had a positive result from either the tuberculin skin test or the
QuantiFERON-TB® Gold test prior to screening) and documentation of having
completed an adequate treatment regimen for latent TB within 1 year prior to the
first administration of study agent. Adequate treatment for latent TB is defined
according to local country guidelines for immunocompromised patients. If no local
guidelines for immunocompromised patients exist, United States (US) guidelines
must be followed. It is the responsibility of the Investigator to verify the
adequacy of previous anti-TB treatment and provide appropriate documentation.
2. Have no signs or symptoms suggestive of active TB upon medical history and/or
physical examination.
3. Have had no recent (within approximately 3 months) close contact with a person
with active TB or if there has been such contact, have been evaluated by a
physician specialising in TB and found not to have evidence of, or require
treatment for latent TB.
- At screening, the results of the following laboratory tests performed at the local
laboratory must be within the limits specified below (note: the Investigator may
consider the participant eligible if the previously abnormal laboratory test result is
within acceptable range on repeat testing. Repeat testing to be done 28 days before
dose administration. If results from the laboratory test completed on the same day as
the lumbar Puncture are outside the limits specified below, the Investigator may
choose to repeat tests and continue the participant in the study, depending on their
clinical assessment of any likely outcome/risks).
1. Haemoglobin =8.5 g/dL (International System of Units [SI]: =85 g/L)
2. White Blood Cells (WBC) count =3.0 x 103 cells/mm3 (SI:= 3.0 x 109 cells/L)
3. Neutrophils =1.5 x 103 cells/mm3 (SI:= 1.5 x 109 cells/L)
4. Lymphocyte count (absolute) =450 cells/mm3 (SI: =0.45 x 109 cells/L)
5. Platelets =100 x 103 cells/mm3 (SI: =100 x 109 cells/L)
6. Serum alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) levels
=1.5 x upper limit of normal (ULN)
7. Total bilirubin levels =1.5 x ULN
8. Serum creatinine =1.5 mg/dL
- Be otherwise healthy on the basis of clinical laboratory tests performed at screening.
If the results of serum chemistry, haematology, or urinalysis tests not specified in
the inclusion criteria above are outside of the normal range, the participant may be
included only if the Investigator judges the abnormalities or deviations from normal
not to be clinically significant or to be appropriate and reasonable for the
population under study.
- A woman, before study entry, must be postmenopausal (amenorrhea for at least 18
months). If a man is heterosexually active with a woman of childbearing potential, he
must agree to use a double-barrier method of birth control and not to donate sperm
during the study and for 6 months after receiving the last dose of study agent.
- Be willing and able to adhere to all of the procedures, prohibitions and restrictions
specified in the protocol.
Exclusion Criteria:
- Research participants who fulfil diagnostic criteria for any type of dementia (e.g.
Alzheimer Dementia, Frontotemporal Dementia (FTD), Diffuse Lewy Body Dementia (DLBD),
Vascular Dementia (VAD), etc) CDR =1.
- Known carriers of a presenilin 1 (PSEN1), presenilin 2 (PSEN2) or Amyloid Precursor
Protein (APP) mutation associated with Autosomal Dominant AD or any other
neurodegenerative disease.
- Prohibited or restricted concomitant medication as detailed in Section 10.1.7.
- Presence of any neurological, psychiatric or medical conditions associated with a
long-term risk of significant cognitive impairment or dementia including but not
limited to pre-manifest Huntington's disease, multiple sclerosis, Parkinson's disease,
Down syndrome, active alcohol/drug abuse or major psychiatric disorders including
current major depressive disorder, schizophrenia, schizoaffective or bipolar disorder.
To quantify abuse is to define this as history of drug or alcohol abuse according to
Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-V) criteria
within 6 months before screening or positive test result for alcohol and/or drugs of
abuse at screening/admission.
- History of latent or active infection of one of the following infectious diseases at
screening: Listeria infection, Histoplasma, Coccidioides, Paracoccidioides,
Pneumocystis, nontuberculous mycobacteria, Blastomyces, Aspergillus, cytomegalovirus
generalised or Herpes zoster infection
- Any cancer or history of cancer in the preceding 5 years (excluding cutaneous basal or
squamous cell cancer resolved by excision).
- Any conditions that are clinically significant and may deem the participant's
participation in an investigational trial unsafe, e.g., symptomatic cardiovascular
disease (including re-vascularisation procedures within the previous year), severe
renal or hepatic failure, any clinically relevant abnormalities in blood parameters
included in local routine assessments, severe loss of vision, hearing or communicative
ability, conditions preventing co-operation or completing the required assessments in
the trial, as judged by the Investigator.
- Any contraindications for Lumbar Puncture.
- Any evidence of intracranial pathology which may affect cognition including but not
limited to brain tumours (benign or malignant), aneurysm or arteriovenous
malformations, territorial stroke (excluding smaller watershed strokes), history of or
recovering haemorrhage (parenchymal or subdural), or obstructive hydrocephalus.
Research participants with an MRI scan demonstrating markers of small vessel disease
(e.g. white matter changes or lacunar infarcts) judged to be clinically insignificant,
or microbleeds are allowed.
- Participation in a clinical trial with an Investigational Medicinal Product (IMP) in
the last 30 days or 90 days in case of biologics.
- Diminished decision-making capacity that renders the individual not capable of
consenting.
- Any other factors in the opinion of the Investigator that could contraindicate the
participation of the research participant into this trial.
|
