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Alipogene Tiparvovec for the Treatment of LPLD Patients

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ClinicalTrials.gov Identifier: NCT02904772
Recruitment Status : Withdrawn (uniQure, has decided not to renew the Marketing Authorization of Glybera in the EU.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)
First Posted : September 19, 2016
Last Update Posted : August 17, 2017
Sponsor:
Collaborator:
Chiesi Farmaceutici S.p.A.
Information provided by (Responsible Party):
UniQure Biopharma B.V.

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.

Condition or disease Intervention/treatment Phase
LPL Deficiency Drug: alipogene tiparvovec Drug: Prednisolone Drug: Cyclosporins Drug: Mycophenolate mofetil Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Multi-centre Trial of Alipogene Tiparvovec for the Treatment of LPLD Patients
Study Start Date : October 2016
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : September 2020


Arm Intervention/treatment
alipogene tiparvovec with IS
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.
Drug: alipogene 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.
Other Name: Glybera

Drug: Prednisolone
IV bolus methylprednisolone 1mg/kg half hour prior to administration

Drug: Cyclosporins
Immuno + group will receive cyclosporine (3 mg/kg/day) from three days prior to until 12 weeks following IMP administration

Drug: Mycophenolate mofetil
Immuno + group will receive Mycophenolate mofetil (2x 1 g/day) from three days prior to until 12 weeks following IMP administration

alipogene tiparvovec without IS
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.
Drug: alipogene 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.
Other Name: Glybera

Drug: Prednisolone
IV bolus methylprednisolone 1mg/kg half hour prior to administration




Primary Outcome Measures :
  1. The Clinical Response of alipogene tiparvovec in LPLD patients [ Time Frame: 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.

  2. The long term effect of alipogene tiparvovec on post prandial metabolism of chylomicrons (ppCM) in LPLD patients. [ Time Frame: 2 years ]
    CM [3H]-activity will be assessed during ppCM testing pre- and post-dose, compared to baseline.


Secondary Outcome Measures :
  1. The effect of alipogene tiparvovec on postprandial metabolism of chylomicrons (ppCM) in LPLD patients with and without immunosuppression treatment, at 14 weeks post-administration. [ Time Frame: Baseline, 14 weeks ]
    CM [3H]-activity will be assessed during ppCM testing pre- and post-dose, compared to baseline.

  2. Immuno response of alipogene tiparvovec by analysis of antibody formation [ Time Frame: Baseline, 1 and 2 years post dose ]
    The immuno response of alipogene tiparvovec will be assessed by measuring the antibody formation compared to baseline.

  3. Immuno response of alipogene tiparvovec by analysis of T-cell response [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02904772


Locations
United States, Pennsylvania
Perelman School of Medicine at The University of Pennsylvania Translational Medicine & Human Genetics
Philadelphia, Pennsylvania, United States, PA19104
Canada, Quebec
Centre hospitalier universitaire de Sherbrooke
Sherbrooke, Quebec, Canada, J1H 5N4
Sponsors and Collaborators
UniQure Biopharma B.V.
Chiesi Farmaceutici S.p.A.
Investigators
Principal Investigator: André Carpentier, MD Centre de recherche du Centre hospitalier universitaire de Sherbrooke

Responsible Party: UniQure Biopharma B.V.
ClinicalTrials.gov Identifier: NCT02904772     History of Changes
Other Study ID Numbers: Gly-CD-001
First Posted: September 19, 2016    Key Record Dates
Last Update Posted: August 17, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Hyperlipoproteinemia Type I
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Cyclosporins
Cyclosporine
Mycophenolic Acid
Prednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Antibiotics, Antineoplastic