Alipogene Tiparvovec for the Treatment of LPLD Patients

NCT02904772 | Withdrawn Phase 2

• 1 other identifier: Gly-CD-001
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 2

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.

Conditions

LPL Deficiency

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• 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

• Immuno response of alipogene tiparvovec by analysis of antibody formation

  Baseline, 1 and 2 years post dose

• Immuno response of alipogene tiparvovec by analysis of T-cell response

  Baseline, 1 and 2 years post dose

Study Arms (2)

alipogene tiparvovec with IS

OTHER

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; Drug: Prednisolone; Drug: Cyclosporins; Drug: Mycophenolate mofetil

alipogene tiparvovec without IS

OTHER

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; Drug: Prednisolone

Interventions

alipogene tiparvovec DRUG

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.

Also known as: Glybera

alipogene tiparvovec with IS; alipogene tiparvovec without IS

Prednisolone DRUG

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

alipogene tiparvovec with IS; alipogene tiparvovec without IS

Cyclosporins DRUG

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

alipogene tiparvovec with IS

Mycophenolate mofetil DRUG

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

alipogene tiparvovec with IS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• UniQure Biopharma B.V.: lead
• Chiesi Farmaceutici S.p.A.: collaborator

Study Sites (2)

Perelman School of Medicine at The University of Pennsylvania Translational Medicine & Human Genetics

Philadelphia, Pennsylvania, PA19104, United States

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

MeSH Terms

Conditions

Hyperlipoproteinemia Type I

Interventions

Alipogene tiparvovec; Prednisolone; Cyclosporins; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Peptides, Cyclic; Macrocyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Officials

• André Carpentier, MD

  Centre de recherche du Centre hospitalier universitaire de Sherbrooke

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2016
• First Posted: September 19, 2016
• Study Start: October 1, 2016
• Primary Completion: June 1, 2020
• Study Completion: September 1, 2020
• Last Updated: August 17, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (1)