Anti-MAG First Administration to Human

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00622609
First received: February 13, 2008
Last updated: March 15, 2012
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Chronic Diseases Associated With Axonal Damage
Cerebrovascular Accident
Drug: GSK249320
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Single-blind, Single Dose, Placebo Controlled, Parallel Group, First Time in Human Study to Assess the Safety, Tolerability, Pharmacokinetics and Immunogenicity of Ascending IV Doses of GSK249320 in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Safety and tolerability of GSK249320 including: adverse events,vital signs,ECG,continuous lead II ECG monitoring,safety laboratory assessments,clinical assessment of peripheral nerve function,nerve conduction testing [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetic parametersAnti-GSK249320 antibody titres [ Time Frame: At various timepoints from pre-dose to Week 52 follow-up ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of ascending single IV doses of GSK249320: Cinf, AUC(0-24), AUC(0-t) and AUC(0-inf) [ Time Frame: At various timepoints from pre-dose to Week 52 follow-up ] [ Designated as safety issue: No ]
  • Anti-GSK249320 Antibody titres: serum samples will be collected for anti-drug (anti-GSK249320) antibody confirmation, titration and neutralization testing [ Time Frame: At various timepoints from pre-dose to Week 52 follow-up ] [ Designated as safety issue: No ]
  • Non-compartmental pharmacokinetic parameters of GSK249320 : Tinf , lz, T1/2, CL and Vss [ Time Frame: At various timepoints from pre-dose to Week 52 follow-up ] [ Designated as safety issue: No ]
  • Novel candidate biomarkers and subsequently discovered biomarkers of the biological response associated with the action of GSK249320 may be identified by application of: [ Time Frame: At various timepoints from pre-dose to Week 52 follow-up ] [ Designated as safety issue: No ]
  • RNA transcriptome analysis of blood samples [ Time Frame: At various timepoints from pre-dose to Week 52 follow-up ] [ Designated as safety issue: No ]
  • Proteome analysis of plasma samples [ Time Frame: At various timepoints from pre-dose to Week 52 follow-up ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: August 2007
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Placebo Comparator
Experimental: GSK249320 Drug: GSK249320
IV Infusion
Other Name: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00622609

Locations
United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21225
Australia, New South Wales
GSK Investigational Site
Randwick, Sydney, New South Wales, Australia, 2031
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00622609     History of Changes
Other Study ID Numbers: MAG103114
Study First Received: February 13, 2008
Last Updated: March 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
first time in human,
MAG
monoclonal antibody,
healthy subjects,
GSK249320,

Additional relevant MeSH terms:
Cerebral Infarction
Brain Infarction
Stroke
Chronic Disease
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on September 16, 2014