NCT01109498

A Study to Determine the Safety and Efficacy in Lipoprotein Lipase-Deficient Subjects After Intramuscular Administration of AMT-011, an Adeno-Associated Viral Vector Expressing Human Lipoprotein LipaseS447X

Status unknown Phase 2/Phase 3 Last updated 29 September 2011

What this trial tests

Phase 2/Phase 3 trial testing Alipogene Tiparvovec (AMT-011), Human LPL [S447X] in Familial Lipoprotein Lipase Deficiency in 14 participants. Status unknown.

Timeline

1 August 2007

Primary endpoint
1 June 2013

1 June 2013

Quick facts

Lead sponsor	Amsterdam Molecular Therapeutics
Phase	Phase 2/Phase 3
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	14
Start date	1 August 2007
Primary completion	1 June 2013
Estimated completion	1 June 2013
Sites	1 location across Canada

Drugs / interventions tested

• Alipogene Tiparvovec (AMT-011), Human LPL [S447X]
• Mycophenolate mofetil (MYCOPHENOLATE MOFETIL) — full drug profile →
• Alipogene Tiparvovec (AMT-011), Human LPL [S447X]
• cyclosporine (cyclosporine) — full drug profile →

Conditions studied

• Familial Lipoprotein Lipase Deficiency — all drugs for Familial Lipoprotein Lipase Deficiency →

Sponsor

Amsterdam Molecular Therapeutics

Who can join

18 and older, any sex, with Familial Lipoprotein Lipase Deficiency. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Reduction of fasting triglyceride (TG) concentrations
  Time frame: 12 weeks
  To achieve a reduction in fasting plasma TG such that the difference in median plasma TG observed before administration and up to 12 weeks after administration represents approximately 40% reduction, on top of a low-fat diet.
• safety profile of AMT-011
  Time frame: 15 years
  Between 6 and 15 years after administration of AMT-011, patients will be annually contacted by phone to monitor delayed adverse events related to administration of AMT-011.

Sponsor's own description

LPLD is a rare autosomal recessive disorder, characterized by the presence of marked chylomicronemia and hence hypertriglyceridemia. Clinically the most severe manifestation of chylomicronemia, is acute pancreatitis, which can be lethal. There is no effective therapy available to modulate the course of the illness and prevent complications for these patients. The current clinical management consists of severe reduction of dietary fat that is hard if not almost impossible to comply with. LPLD subjects continue to experience pancreatitis attacks, and are admitted to intensive care units on several occasions.

Alipogene tiparvovec corrects or restores lipoprotein lipase (LPL) function long term, and hence reverses some symptoms, halts the disease progression and prevents further complications. Alipogene tiparvovec gene therapy ensures that a catabolically beneficial variant of the human LPL gene, LPL\[S447X\] is expressed and active in the relevant tissues in humans. Delivery of the gene is realized via intramuscular injection of an adeno-associated viral vector, pseudotyped with AAV1 capsids.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer.
   Costa Verdera H, Kuranda K, Mingozzi F. · · 2020 · cited 493× · PMID 31972133 · DOI 10.1016/j.ymthe.2019.12.010
2. Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial.
   Gaudet D, Méthot J, Déry S, Brisson D, et al · · 2013 · cited 293× · PMID 22717743 · DOI 10.1038/gt.2012.43
3. The Skeletal Muscle Environment and Its Role in Immunity and Tolerance to AAV Vector-Mediated Gene Transfer.
   Boisgerault F, Mingozzi F. · · 2015 · cited 42× · PMID 26122097 · DOI 10.2174/1566523215666150630121750
4. A versatile toolkit for overcoming AAV immunity.
   Li X, Wei X, Lin J, Ou L. · · 2022 · cited 31× · PMID 36119036 · DOI 10.3389/fimmu.2022.991832
5. Improving clinical efficacy of adeno associated vectors by rational capsid bioengineering.
   Sen D. · · 2014 · cited 19× · PMID 25425174 · DOI 10.1186/s12929-014-0103-1
6. Recombinant adeno-associated virus vectors in the treatment of rare diseases.
   Hastie E, Samulski RJ. · · 2015 · cited 18× · PMID 27668135 · DOI 10.1517/21678707.2015.1039511
7. Cellular unfolded protein response against viruses used in gene therapy.
   Sen D, Balakrishnan B, Jayandharan GR. · · 2014 · cited 14× · PMID 24904562 · DOI 10.3389/fmicb.2014.00250