The aim of the study is to provide further confirmatory evidence of clinical benefit in LPLD patients treated with alipogene tiparvovec by assessing both the "clinical response" (as defined by a range of parameters), and "the metabolic response" (postprandial CM metabolism) in LPLD patients with and without an immunosuppressant regimen.
This is a prospective, interventional, randomised, open-label, parallel group study evaluating the clinical response as well as the dynamics of postprandial chylomicron metabolism in patients treated with alipogene tiparvovec with and without immunosuppressants. The study will be conducted in 12 LPLD patients who will be randomised into the Immuno+ (cyclosporin and mycophenolate mofetil) or the Immuno- group.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
A dose of 1x10(\*12) gc/kg alipogene tiparvovec (Glybera) of body weight administered as a single set of intramuscular injections at multiple sites in multiple muscles of both upper legs and if necessary, the lower legs.
IV bolus methylprednisolone 1mg/kg half hour prior to administration
Immuno + group will receive cyclosporine (3 mg/kg/day) from three days prior to until 12 weeks following IMP administration
Perelman School of Medicine at The University of Pennsylvania Translational Medicine & Human Genetics
Philadelphia, Pennsylvania, United States
Centre hospitalier universitaire de Sherbrooke
Sherbrooke, Quebec, Canada
The Clinical Response of alipogene tiparvovec in LPLD patients
The overall clinical response of alipogene tiparvovec in LPLD patients will be assessed compared to baseline, by a combination of measurements, of which each gives relevant information to obtain enough and solid evidence in a small trial. Each of these outcome measures will be evaluated in combination with the results of other measures (to get an overall conclusion relating the clinical response). Descriptive methods will be used (so no formal statistical analyses will be performed), due to the specific nature and the small sample size of a rare disease trial.
Time frame: 2 years
The long term effect of alipogene tiparvovec on post prandial metabolism of chylomicrons (ppCM) in LPLD patients.
CM \[3H\]-activity will be assessed during ppCM testing pre- and post-dose, compared to baseline.
Time frame: 2 years
The effect of alipogene tiparvovec on postprandial metabolism of chylomicrons (ppCM) in LPLD patients with and without immunosuppression treatment, at 14 weeks post-administration.
CM \[3H\]-activity will be assessed during ppCM testing pre- and post-dose, compared to baseline.
Time frame: Baseline, 14 weeks
Immuno response of alipogene tiparvovec by analysis of antibody formation
The immuno response of alipogene tiparvovec will be assessed by measuring the antibody formation compared to baseline.
Time frame: Baseline, 1 and 2 years post dose
Immuno response of alipogene tiparvovec by analysis of T-cell response
T-cell responses against alipogene tiparvovec will be assessed by measuring the T-cell response compared to baseline.
Time frame: Baseline, 1 and 2 years post dose
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Immuno + group will receive Mycophenolate mofetil (2x 1 g/day) from three days prior to until 12 weeks following IMP administration