Back to resultsAlipogene Tiparvovec for the Treatment of LPLD Patients
Primary Purpose
LPL Deficiency
Status
Withdrawn
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
alipogene tiparvovec
Prednisolone
Cyclosporins
Mycophenolate mofetil
Sponsored by
About this trial
This is an interventional treatment trial for LPL Deficiency
Eligibility 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.
Sites / Locations
- Perelman School of Medicine at The University of Pennsylvania Translational Medicine & Human Genetics
- Centre hospitalier universitaire de Sherbrooke
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
alipogene tiparvovec with IS
alipogene tiparvovec without IS
Arm Description
Patients in the Immuno+ group will receive an immunosuppressant regimen to be initiated three days prior to alipogene tiparvovec administration. The regimen is to be continued for 12 weeks: Cyclosporins (3 mg/kg/day) and mycophenolate mofetil (2 x 1 g/day). Patients will receive IV bolus of 1mg/kg of methyl Prednisolone half an hour prior to IMP administration.
Patients in the Immuno- group will not receive an immunosuppressant regimen during 12 weeks. Patients will receive IV bolus of 1mg/kg of methyl Prednisolone half an hour prior to IMP administration.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
Full Information
NCT ID
NCT02904772
First Posted
May 10, 2016
Last Updated
August 14, 2017
Sponsor
UniQure Biopharma B.V.
Collaborators
Chiesi Farmaceutici S.p.A.
1. Study Identification
Unique Protocol Identification Number
NCT02904772
Brief Title
Alipogene Tiparvovec for the Treatment of LPLD Patients
Official Title
An Open Label, Multi-centre Trial of Alipogene Tiparvovec for the Treatment of LPLD Patients
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Withdrawn
Why Stopped
uniQure, has decided not to renew the Marketing Authorization of Glybera in the EU. This decision is not related to any safety, efficacy or quality issue
Study Start Date
October 2016 (undefined)
Primary Completion Date
June 2020 (Anticipated)
Study Completion Date
September 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UniQure Biopharma B.V.
Collaborators
Chiesi Farmaceutici S.p.A.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
LPL Deficiency
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
alipogene tiparvovec with IS
Arm Type
Other
Arm Description
Patients in the Immuno+ group will receive an immunosuppressant regimen to be initiated three days prior to alipogene tiparvovec administration. The regimen is to be continued for 12 weeks: Cyclosporins (3 mg/kg/day) and mycophenolate mofetil (2 x 1 g/day). Patients will receive IV bolus of 1mg/kg of methyl Prednisolone half an hour prior to IMP administration.
Arm Title
alipogene tiparvovec without IS
Arm Type
Other
Arm Description
Patients in the Immuno- group will not receive an immunosuppressant regimen during 12 weeks. Patients will receive IV bolus of 1mg/kg of methyl Prednisolone half an hour prior to IMP administration.
Intervention Type
Drug
Intervention Name(s)
alipogene tiparvovec
Other Intervention Name(s)
Glybera
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Intervention Description
IV bolus methylprednisolone 1mg/kg half hour prior to administration
Intervention Type
Drug
Intervention Name(s)
Cyclosporins
Intervention Description
Immuno + group will receive cyclosporine (3 mg/kg/day) from three days prior to until 12 weeks following IMP administration
Intervention Type
Drug
Intervention Name(s)
Mycophenolate mofetil
Intervention Description
Immuno + group will receive Mycophenolate mofetil (2x 1 g/day) from three days prior to until 12 weeks following IMP administration
Primary Outcome Measure Information:
Title
The Clinical Response of alipogene tiparvovec in LPLD patients
Description
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
Title
The long term effect of alipogene tiparvovec on post prandial metabolism of chylomicrons (ppCM) in LPLD patients.
Description
CM [3H]-activity will be assessed during ppCM testing pre- and post-dose, compared to baseline.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
The effect of alipogene tiparvovec on postprandial metabolism of chylomicrons (ppCM) in LPLD patients with and without immunosuppression treatment, at 14 weeks post-administration.
Description
CM [3H]-activity will be assessed during ppCM testing pre- and post-dose, compared to baseline.
Time Frame
Baseline, 14 weeks
Title
Immuno response of alipogene tiparvovec by analysis of antibody formation
Description
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
Title
Immuno response of alipogene tiparvovec by analysis of T-cell response
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
André Carpentier, MD
Organizational Affiliation
Centre de recherche du Centre hospitalier universitaire de Sherbrooke
Official's Role
Principal Investigator
Facility Information:
Facility Name
Perelman School of Medicine at The University of Pennsylvania Translational Medicine & Human Genetics
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
PA19104
Country
United States
Facility Name
Centre hospitalier universitaire de Sherbrooke
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Alipogene Tiparvovec for the Treatment of LPLD Patients
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