Alipogene Tiparvovec for the Treatment of LPLD Patients

LPL Deficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02904772
• Other study ID #: Gly-CD-001
• Status: Withdrawn
• Phase: Phase 2
• First received: May 10, 2016
• Last updated: August 14, 2017
• Start date: October 2016
• Est. completion date: September 2020

Study information

• Verified date: July 2017
• Source: UniQure Biopharma B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2020
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hyperlipoproteinemia Type I
• LPL Deficiency

Intervention

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.
• Prednisolone
IV bolus methylprednisolone 1mg/kg half hour prior to administration
• Cyclosporins
Immuno + group will receive cyclosporine (3 mg/kg/day) from three days prior to until 12 weeks following IMP administration
• Mycophenolate mofetil
Immuno + group will receive Mycophenolate mofetil (2x 1 g/day) from three days prior to until 12 weeks following IMP administration

Locations

Country	Name	City	State
Canada	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec
United States	Perelman School of Medicine at The University of Pennsylvania Translational Medicine & Human Genetics	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
UniQure Biopharma B.V.	Chiesi Farmaceutici S.p.A.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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