GSK249320 is a monoclonal antibody directed against myelin associated glycoprotein (MAG), a
protein that inhibits axonal regeneration. GSK249320 acts as a MAG antagonist, and through
this activity it is hypothesised that it will enhance recovery from neuronal degeneration
following acute axonal injury, which occurs in spinal cord injury or stroke.
- Healthy adult men or women of non-child bearing potential (i.e. post-menopausal or
surgically sterile e.g. hysterectomy or bilateral oophorectomy). If necessary,
postmenopausal status will be confirmed by serum FSH and oestradiol concentrations at
screening. Surgical sterility will be defined as females who have had a documented
hysterectomy or bilateral oophorectomy.
- Between 18 and 60 years of age inclusive.
- Body weight >/ 60 kg and BMI within the range 19-29.9 kg/m2 inclusive.
- Healthy as judged by responsible physician with no clinically significant abnormality
identified on the medical or laboratory evaluation. A subject with a clinical
abnormality or laboratory parameters outside the reference range for this age group
may be included only if the Investigator considers that the finding will not introduce
additional risk factors and will not interfere with the study procedures.
- A 12-lead ECG at pre-study screening which in the opinion of the Investigator or
his/her designee has no abnormalities that will compromise safety in this study.
- Normal clinical neurological exam, normal QST results, and normal pattern of
conduction latencies in medial, ulnar, sural, tibial and peroneal nerves at screening.
- Signed and dated written informed consent prior to admission to the study.
- The subject is able to understand and comply with protocol requirements, instructions
and protocol-stated restrictions.
- Positive drug/ alcohol screen at screening or baseline.
- Positive pre-study HIV, Hepatitis B surface antigen or positive Hepatitis C antibody
result at screening.
- History of acute neuronal injury (central or peripheral) within the previous 12
months, peripheral neuropathy or neuritis, neurodegenerative disorders or other
neurological diseases, including conditions which are known or hypothesised to be
associated with disruption in the blood-brain barrier (BBB).
- Considered to be at a high risk of developing a stroke including a history of carotid
artery disease or surgery, transient ischaemic attacks, reversible ischaemic
neurological deficits or other abnormalities of the brain vessels, including but not
limited to berry aneurysms or arteriovenous malformations.
- History of regular alcohol consumption averaging >7 drinks/week for women or >14
drinks/week for men. One drink is equivalent to (12 g alcohol) = 5 ounces (150 mL) of
wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of 80 proof distilled
spirits) within 6 months of screening.
- Subjects who smoke 10 or more cigarettes per day. Subjects who smoke <10 cigarettes
per day may be admitted into the study but will be asked to refrain from smoking for
at least 24 hours before the planned day of admission into the unit. They will NOT be
allowed to smoke during their stay in the unit.
- The subject is unable to abstain from strenuous physical activity for 72 h prior to
each clinic visit where safety lab tests are conducted.
- The subject has participated in a clinical trial and has received an investigational
product within the following time period prior to the dosing day in the current study:
30 days, 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer).
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
supplements (including St John's Wort) within 7 days or 5 half-lives (whichever is
longer) prior to the first dose of study medication.
- Where participation in study would result in donation of blood in excess of 500 mL
within a 56 day period.
- Previous exposure to humanised antibody therapy for any reason.
- Unwillingness of the male subjects to abstain from sexual intercourse with pregnant or
lactating women from the time of the first dose of study medication until five half
lives following administration of the dose of study medication. This may be increased
depending on PK analysis during the study.
- Unwillingness of the male subject to use a condom/spermicide in addition to having
their female partner use another form of contraception such as an intra-uterine device
(IUD), diaphragm with spermicide, oral contraceptives, injectable progesterone,
subdermal implants or a tubal ligation if the woman could become pregnant from the
time of the first dose of study medication until five half lives following
administration of the last dose of study medication. The duration of the period during
which contraception must be practiced may be modified during the study, depending on
data emerging from PK analysis. The mean half-life predicted for GSK249320 is 30 days
- Female subjects with positive urine/serum pregnancy test result at screening or prior
to first dose
- Status as a "vulnerable" subject, defined by the US Food and Drug Administration (FDA)
Code of Federal Regulations; 45 CFR, Section 46, Subparts B and C.