Alipogene Tiparvovec for the Treatment of LPLD Patients

An Open Label, Multi-centre Trial of Alipogene Tiparvovec for the Treatment of LPLD Patients

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.

Study Overview

• Status: Withdrawn
• Conditions: LPL Deficiency
• Intervention / Treatment: Drug: alipogene tiparvovec; Drug: Prednisolone; Drug: Cyclosporins; Drug: Mycophenolate mofetil

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
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, PA19104
      • Perelman School of Medicine at The University of Pennsylvania Translational Medicine & Human Genetics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	Baseline, 1 and 2 years post dose

Collaborators and Investigators

• Sponsor: UniQure Biopharma B.V.
• Collaborators: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: André Carpentier, MD, Centre de recherche du Centre hospitalier Universitaire de Sherbrooke

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): September 1, 2020

Study Registration Dates

• First Submitted: May 10, 2016
• First Submitted That Met QC Criteria: September 13, 2016
• First Posted (Estimate): September 19, 2016

Study Record Updates

• Last Update Posted (Actual): August 17, 2017
• Last Update Submitted That Met QC Criteria: August 14, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hyperlipoproteinemia Type I; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Prednisolone; Mycophenolic Acid; Cyclosporine; Cyclosporins
• Other Study ID Numbers: Gly-CD-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No