LPL Deficiency
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGalipogene tiparvovec
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.
DRUGPrednisolone
IV bolus methylprednisolone 1mg/kg half hour prior to administration
DRUGCyclosporins
Immuno + group will receive cyclosporine (3 mg/kg/day) from three days prior to until 12 weeks following IMP administration
DRUGMycophenolate mofetil
Immuno + group will receive Mycophenolate mofetil (2x 1 g/day) from three days prior to until 12 weeks following IMP administration
Sponsors
Chiesi Farmaceutici S.p.A.
UniQure Biopharma B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main inclusion criteria are: * Patients with a history of severe or multiple pancreatitis attacks despite dietary fat restriction. * Genetically confirmed diagnosis of LPLD * Post-heparin plasma LPL protein mass \> 5% of normal * LPL activity ≤20% of normal (in post- heparin plasma) * Fasting plasma TG concentration \>10 mmol/L. Main
Exclusion criteria
are: * Females with a positive pregnancy test or who are breastfeeding, or on contraceptive use. * Patients with a positive HIV, Hepatitis B, Hepatitis C or being positive for tuberculosis. * Patients under treatment with antiplatelet or other anti-coagulants. * Patient allergic to or having a condition that prohibits the use of immunosuppressants.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Clinical Response of alipogene tiparvovec in LPLD patients | 2 years | 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. |
| The long term effect of alipogene tiparvovec on post prandial metabolism of chylomicrons (ppCM) in LPLD patients. | 2 years | CM \[3H\]-activity will be assessed during ppCM testing pre- and post-dose, compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The effect of alipogene tiparvovec on postprandial metabolism of chylomicrons (ppCM) in LPLD patients with and without immunosuppression treatment, at 14 weeks post-administration. | Baseline, 14 weeks | CM \[3H\]-activity will be assessed during ppCM testing pre- and post-dose, compared to baseline. |
| Immuno response of alipogene tiparvovec by analysis of antibody formation | Baseline, 1 and 2 years post dose | The immuno response of alipogene tiparvovec will be assessed by measuring the antibody formation compared to baseline. |
| Immuno response of alipogene tiparvovec by analysis of T-cell response | Baseline, 1 and 2 years post dose | T-cell responses against alipogene tiparvovec will be assessed by measuring the T-cell response compared to baseline. |
Countries
Canada, United States
Outcome results
None listed