| City: |
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Baltimore |
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State:
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MD |
| Zip Code: |
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21287 |
| Conditions: |
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Amyotrophic Lateral Sclerosis |
| Purpose: |
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The drug being tested in this study is GSK1223249. It is being developed by GlaxoSmithKline
to treat symptoms in patients with Amyotrophic Lateral Sclerosis (ALS).
The drug works by inhibiting the protein that prevents nerve growth.
This will be the first time the drug will be given to man. The trial is expected to involve
approximately 76 patients. The study objective is to investigate the tolerability, safety
and the way the body handles GSK1223249 after a range of single doses or repeat dose
escalation in patients with ALS.
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| Study summary: |
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This is the first-time-in-human (FTIH) phase I/IIa study of GSK1223249, a humanised
monoclonal antibody against Nogo-A, a neurite outgrowth inhibitor hypothesised to be
involved in the pathophysiology of amyotrophic lateral sclerosis (ALS) and some other
neurodegenerative disorders. This study will be a randomized, placebo-controlled,
double-blind, sequential dose escalation, 2-part fusion protocol. Approximately 76 patients
with ALS will be enrolled. In Part 1, single escalating intravenous (i.v.) doses of
GSK1223249 are planned to be evaluated in 5 sequential patient cohorts (2 placebo and 6
active in each cohort) to determine single dose safety and pharmacokinetics (PK). Part 2
will also be of a sequential dose escalating design, but patients in each of the planned 3
cohorts (3 placebo, 9 active in each cohort) will receive 2 repeat i.v. doses approximately
4 weeks apart where, safety and PK will also be evaluated. In two cohorts in Part 1 and all
cohorts in Part 2, blood samples and skeletal muscle biopsies will be taken from patients
before and at the end of treatment to demonstrate whether or not GSK1223249 binds to its
target and produces any measurable pharmacodynamic effect. Patients in both parts will
receive their first dose in a hospital-based unit where they will be monitored for at least
24 hours post-dose before being discharged to be followed on an out-patient basis. In each
cohort in part 1, the first four subjects will be dosed in a staggered manner such that only
one will receive the dose in any 24 hours. Dosing of the first four subjects in the first
cohort of part 2 will also be staggered in a similar manner. |
| Criteria: |
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Inclusion Criteria:
- Patients with diagnosis of familial or sporadic ALS, defined as meeting the possible,
laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS
according to the revised World Federation of Neurology El Escorial criteria [Rix
Brooks 2000].
- Onset of muscle weakness within 60 months of study entry.
- Patients who have low Slow Inspiratory Vital Capacity (SVC) below that what is
predicted for age and sex can be included into the study at the discretion of the
investigator as long as they are NOT respiratory insufficient.
- If on any medication (including riluzole), these must have been stable within the
previous one month. (See also 'Concomitant Medications' - Section 8).
- Age 18 - 80 years inclusive.
- Male or Female of non-childbearing potential (NCBP) defined as follows:
Pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal
defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with
simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and oestradiol < 40 pg/ml
(<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose
menopausal status is in doubt will be required to use one of the contraception methods in
Section 7.1.1, if they wish to continue their HRT during the study. Otherwise, they must
discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.
For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy
and the blood draw; this interval depends on the type and dosage of HRT. Following
confirmation of their post-menopausal status, they can resume use of HRT during the study
without use of a contraceptive method.
- Male subjects must agree to use one of the contraception methods listed in Section
7.1.2. This criterion must be followed from the time of the first dose of study
medication until the last follow-up visit.
- QTcB < 500 msec or uncorrected QT <600msec (machine or manual overread). If subject
has bundle branch block then criteria is QTcB < 530 msec.
- A Body Mass Index that at the discretion of the investigator is acceptable for
inclusion into the study.
- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.
Exclusion Criteria:
- Patients with other neuromuscular disorders (in addition to their ALS diagnosis),
unless the investigator determines that such additional disorder will not affect
safety or other measures in this study.
- Patients with evidence of dementia or psychiatric illness which, in the
investigator's opinion, is likely to prevent them from a full understanding of and/or
compliance with the study requirements and procedures.
- Patients with abnormalities detected during the screening evaluations which, in the
investigator's medical judgement, are sufficiently significant to exclude them from
participation in the study.
- Patients who have participated in a clinical trial involving receipt of a
biopharmaceutical product within 6 months prior to the first dosing day.
- Exposure to more than four new investigational products within 12 months prior to the
first dosing day.
- The subject has a positive drugs of abuse test at the screening or pre dose visit. A
minimum list of drugs that will be screened for include amphetamines, barbiturates,
cocaine, opiates and benzodiazepines. Subjects who are on any of these drugs by
prescription for medical reasons may be considered by the investigator for inclusion
if they fulfil other entry criteria.
- The subject has a positive alcohol test at the pre-dose visit. History of regular
excessive alcohol consumption within 6 months of the study defined as:
- For European sites: an average weekly intake of > 28 units for males or >21 units for
females. One unit is equivalent to 8g of alcohol: a half-pint (~240mL) of beer, 1
glass (125mL) of wine or 1 (25mL) measure of spirits.
- For North American sites: an average weekly intake of >21 drinks for males or >14
drinks for women. One drink is equivalent to 12 g alcohol: 12 ounces (360mL) of
beer, 5 ounces (150mL) of wine or 1.5 ounces (45mL) of 80 proof distilled spirits.
- History of sensitivity to GSK1223249, or components thereof, or a history of drugs or
other allergies that, in the opinion of the investigator or GSK Medical Monitor,
contraindicates their participation.
- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.
- Females of childbearing potential, pregnant females as determined by positive serum
or urine beta hCG test at screening or prior to dosing, or lactating females.
- Patients who have received any type of vaccination in the last 3 weeks before study
drug administration.
- Unwillingness or inability to follow the procedures outlined in the protocol
- Subjects who will undergo muscle biopsies (cohorts 3-optional 5, 6, 7 and 8 will not
be eligible for inclusion, if any of the following criteria apply:
Patients with wasted deltoids (MRC score ≤ 2) and patients with normal deltoids (MRC score
5).
Patients who cannot achieve normal coagulation in the peri-operative period and those who
may otherwise be at higher risk of bleeding complications |
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| Study is available at: |
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GSK Investigational Site
Baltimore, MD 21287
United States
Primary Contact:
US GSK Clinical Trials Call Center
Email: GSKClinicalSupportHD@gsk.com
Phone: 877-379-3718
Secondary Contact:
US GSK Clinical Trials Call Center
Email: GSKClinicalSupportHD@gsk.com
Phone: 877-379-3718 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 23, 2011 |
Modifications to
this listing: |
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above to view all information about this clinical trial. |
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