This study is intended to enable a possible transition to intramuscular (IM) or subcutaneous (SQ) administration for subsequent studies with GSK933776 by characterizing the safety, tolerability, PK and pharmacodynamic profiles, and immunogenicity of GSK933776 following IM and SQ administration in healthy volunteers. Such alternate routes of administration may provide more options in the selection of an efficacious dose for subsequent development in patients with geographic atrophy. There will be four treatment arms in the study and participants will be assigned to 1 of 4 possible treatment arms in a 1:1:1:1 ratio. The planned number of evaluable participants for this study is 24 with 6 participants completing all critical assessments in each of the four treatment arms. The total duration of participation from screening to follow-up for Treatment Arms A, B and D (single dose of GSK933776), will be approximately 113 days and total duration for Treatment Arm C (repeat dose of GSK933776) will be approximately 134 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Antibody solution for subcutaneous injection with unit dose strength of 50mg/mL administered as 200 mg single dose or as repeat dose of 50 mg weekly for 4 weeks
Antibody solution for intramuscular injection with unit dose strength of 50mg/mL administered as 200 mg single dose
Antibody solution for intravenous injection with unit dose strength of 50mg/mL administered as 200 mg single dose through an IV catheter over approximately 1 hour
GSK Investigational Site
Overland Park, Kansas, United States
Relative bioavailability of GSK933776 after single dose SQ or IM administration as compared to IV infusion
Bioavailability is defined as the rate and extent to which drug reaches the systemic circulation. The relative bioavailability will be calculated from the ratio of area under concentration time curve from time zero to infinity (AUC \[0-infinity\]) following single dose SQ and IM injection to intravenous (IV) infusion
Time frame: Blood samples will be collected at following time points: pre-dose and at (0.25, 0.5, 0.75, 1, 2, 4 hours only for IV infusion), 6, 24, 48, 72, 96, 120, 216, 336, 504, 672, 1344 and 2016 hours post dose
Relative bioavailability of GSK933776 after repeat dose SQ administration as compared to IV infusion
Bioavailability is defined as the rate and extent to which drug reaches the systemic circulation. The relative bioavailability will be calculated from the ratio of AUC (0-infinity) following SQ repeat dose injections to intravenous (IV) infusion
Time frame: Blood samples will be collected at following time points: pre-dose, 6, 24, 48, 72, 96 and 120 hours post dose in each of the 4 dosing weeks and additionally at 216, 336, 504, 672, 1344 and 2016 hours post last dose
Composite of PK parameters of GSK933776 following single dose IM and SQ administration as compared to IV administration
PK parameters include: area under the concentration-time curve over the dosing interval (AUC\[0-tau\]), maximum concentration (Cmax), time of occurrence of Cmax (Tmax), terminal phase half-life (T1/2), clearance, and volume of distribution as data permit
Time frame: Samples will be collected at following time points: pre-dose and at (0.25, 0.5, 0.75, 1, 2, 4 hours only for IV infusion), 6, 24, 48, 72, 96, 120, 216, 336, 504, 672, 1344 and 2016 hours post dose
Composite of PK parameters of GSK933776 following repeat dose SQ administration as compared to IV administration
PK parameters include: AUC(0-tau), Cmax, Tmax, T1/2, clearance, and volume of distribution as data permit
Time frame: Blood samples will be collected at following time points: pre-dose, 6, 24, 48, 72, 96 and 120 hours post dose in each of the 4 dosing weeks and additionally at 216, 336, 504, 672, 1344 and 2016 hours post last dose.
Number of participants with adverse events as a measure of safety and tolerability following single dose administration
AEs will be collected from the start of Study Treatment and until the follow-up contact
Time frame: Up to 113 days
Clinical observation following IV, SQ and IM single dose administration as a measure of safety and tolerability
AEs will be collected from the start of Study Treatment and until the follow-up contact
Time frame: Up to 134 days
Clinical observation following IV, SQ and IM repeat dose administration as a measure of safety and tolerability
Clinical observation include: physical examination, medical history, and review of concomitant medication
Time frame: Up to 113 days
Vital sign measurement following single dose administration as a measure of safety and tolerability
Vital sign measurements will include systolic and diastolic blood pressure, pulse rate, and body temperature measurement.
Time frame: Up to 134 days
Vital sign measurement following repeat dose administration as a measure of safety and tolerability
Vital sign measurements will include systolic and diastolic blood pressure, pulse rate, and body temperature measurement.
Time frame: Up to 134 days
Electrocardiogram (ECG) measurement following single dose administration to assess safety and tolerability
12-lead ECGs will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate (QTc interval).
Time frame: Up to 113 days
ECG measurement following repeat dose administration to assess safety and tolerability
12-lead ECGs will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc interval.
Time frame: Up to 134 days
Clinical laboratory parameters assessment following single dose administration as a measure of safety and tolerability
Clinical laboratory assessment include: hematology, clinical chemistry, urinalysis and additional parameters.
Time frame: Up to 113 days
Clinical laboratory parameters assessment following repeat dose administration as a measure of safety and tolerability
Clinical laboratory assessment include: hematology, clinical chemistry, urinalysis and additional parameters.
Time frame: Up to 134 days
Plasma concentrations of GSK933776, total amyloid beta (AB), total AB fragments, as well as unbound concentrations of AB, fragments containing the epitope 1-22, as data permit following single dose administrationof GSK933776
The relationship between plasma concentration of GSK933776 and plasma concentration of total and free amyloid beta will be explored as data permit
Time frame: Up to 113 days
Plasma concentration of GSK933776, AB, total AB fragments, as well as unbound concentrations of AB, fragments containing the epitope 1-22, as data permit following repeat dose administration
The relationship between plasma concentration of GSK933776 and plasma concentration of total and free amyloid beta will be explored as data permit
Time frame: Up to 134 days
Presence of antibodies to GSK933776 in serum samples following single dose administration of GSK933776
To characterize the immunogenicity profile of GSK933776 following IV, IM and SQ administration. Samples will be analyzed for the presence of anti-GSK933776 antibodies by immuno-electrochemiluminescent (ECL) screening and neutralization assays.
Time frame: Up to 113 days
Presence of antibodies to GSK933776 in serum samples following repeat dose administration
To characterize the immunogenicity profile of GSK933776 following IV, IM and SQ administration. Samples will be analyzed for the presence of anti-GSK933776 antibodies by immuno-electrochemiluminescent (ECL) screening and neutralization assays.
Time frame: Up to 134 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.