Intravenous ACP-501 for Familial LCAT Deficiency (rhLCAT)
Condition: Familial LCAT Deficiency
MeSH terms: Lecithin Cholesterol Acyltransferase Deficiency
Study type: Observational

Summary: 
      Background:

        -  High density lipoprotein (HDL), or good cholesterol, moves cholesterol from the artery
           walls back to the liver. A blood enzyme known as LCAT maintains HDL levels and helps it
           remove cholesterol from the body. Familial LCAT deficiency (FLD) is a genetic disease
           that results in low levels or total absence of LCAT. People with FLD often have kidney
           problems, and may develop kidney failure. Researchers think that the clinical problems
           of FLD can be prevented or even reversed by replacing the defective enzyme.

        -  There are no drugs that increase LCAT. It has to be artificially made and infused into
           the body. The artificial LCAT is called recombinant human LCAT, or ACP-501. Researchers
           want to see how well it works in one person with FLD and poor kidney function.

      Objectives:

      - To see whether ACP-501 can improve the symptoms of FLD.

      Eligibility:

      - One person (the study participant) with FLD.

      Design:

        -  The participant will be screened with a physical exam and medical history. Blood samples
           will be collected.

        -  The participant will receive ACP-501 and remain in the hospital for 24 hours for regular
           blood tests. The participant may stay in the hospital or return for daily clinic visits
           until it is time for the next dose. The second dose will be given on Day 4 or Day 8.

        -  If an optimal dose has not yet been identified, a third dose will be given 7 days after
           the second dose.

        -  The participant will then go home, but must return to the hospital for ACP-501 infusions
           and blood tests every 1 or 2 weeks, as needed. Every 3 months, the participant will have
           a full clinic visit with blood tests and other studies.
    

Detailed description: 
      This primary objective of the study was to use ACP-501 (recombinant LCAT - rhLCAT) as an
      Expanded Access Protocol in order for one named subject with Familial LCAT Deficiency (FLD)
      with the hope of slowing or preventing the progression of renal dysfunction and eliminating
      the need for dialysis. This was a first-in-human study of ACP-501 (rhLCAT) in a subject with
      FLD. The safety and tolerability of rhLCAT, was assessed after multiple infusions. The
      pharmacokinetics (PK) of rhLCAT and its effect on the pharmacodynamics (PD) of HDL-C and HDL
      subpopulations was also be assessed. The duration of the PK and PD parameters will inform
      future multiple dose studies with respect to dose (mg/kg) and dosing interval. The current
      protocol completed the primary objection and has shifted to the secondary analysis of samples
      that were collected. FLD is an extremely rare generic disorders and there are too few
      subjects to design additional phase 1 trials and these longitudinal samples demonstrating the
      appearance of normal HDL along with possible biomarkers will be helpful and can help guide
      the design of a small definitive phase II/II trial.
    

Intervention name(s): Recombinant LCAT
Intervention type(s): Drug
Intervention description(s): iv infusion
Observational model: Other
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Single patient
      
Keywords: Recombinant LCAT; Natural History