Alipogene Tiparvovec for the Treatment of LPLD Patients

Sponsor
UniQure Biopharma B.V. (Industry)
Overall Status
Withdrawn
CT.gov ID
NCT02904772
Collaborator
Chiesi Farmaceutici S.p.A. (Industry)
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Study Details

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.

Condition or Disease Intervention/Treatment Phase
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 Design

Study Type:
Interventional
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 :
Oct 1, 2016
Anticipated Primary Completion Date :
Jun 1, 2020
Anticipated Study Completion Date :
Sep 1, 2020

Arms and Interventions

Arm Intervention/Treatment
Other: 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 Names:
  • 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

    Other: 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 Names:
  • Glybera
  • Drug: Prednisolone
    IV bolus methylprednisolone 1mg/kg half hour prior to administration

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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 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. [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 [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 [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Perelman School of Medicine at The University of Pennsylvania Translational Medicine & Human Genetics Philadelphia Pennsylvania United States PA19104
    2 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    UniQure Biopharma B.V.
    ClinicalTrials.gov Identifier:
    NCT02904772
    Other Study ID Numbers:
    • Gly-CD-001
    First Posted:
    Sep 19, 2016
    Last Update Posted:
    Aug 17, 2017
    Last Verified:
    Jul 1, 2017
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 17, 2017